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<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Explor BioMat-X</journal-id>
<journal-id journal-id-type="publisher-id">EBMX</journal-id>
<journal-title-group>
<journal-title>Exploration of BioMat-X</journal-title>
</journal-title-group>
<issn pub-type="epub">2996-9476</issn>
<publisher>
<publisher-name>Open Exploration Publishing</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.37349/ebmx.2024.00022</article-id>
<article-id pub-id-type="manuscript">101322</article-id>
<article-categories>
<subj-group>
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A review of biopolymer innovations in oculoplastic surgery: reconstruction of eyelid, lacrimal, and orbital structures</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2756-3973</contrib-id>
<name>
<surname>Kulbay</surname>
<given-names>Merve</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/visualization/">Visualization</role>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/">Project administration</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing—original draft</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing—review &amp; editing</role>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1662-6900</contrib-id>
<name>
<surname>Wu</surname>
<given-names>Kevin Y.</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing—review &amp; editing</role>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-4096-7037</contrib-id>
<name>
<surname>Hocini</surname>
<given-names>Adam</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/visualization/">Visualization</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing—original draft</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing—review &amp; editing</role>
<xref ref-type="aff" rid="I3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8323-6761</contrib-id>
<name>
<surname>Daigle</surname>
<given-names>Patrick</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/supervision/">Supervision</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing—review &amp; editing</role>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="editor">
<name>
<surname>Zeng</surname>
<given-names>Rongchang</given-names>
</name>
<role>Academic Editor</role>
<aff>Shandong University of Science and Technology (SDUST), China</aff>
</contrib>
</contrib-group>
<aff id="I1">
<sup>1</sup>Department of Ophthalmology &amp; Visual Sciences, McGill University, Montréal, QC H4A0A4, Canada</aff>
<aff id="I2">
<sup>2</sup>Division of Ophthalmology, Department of Surgery, University of Sherbrooke, Sherbrooke, QC J1K2R1, Canada</aff>
<aff id="I3">
<sup>3</sup>Faculty of Medicine, Université de Montréal, Montréal, QC H3T1J4, Canada</aff>
<author-notes>
<corresp id="cor1">
<bold>
<sup>*</sup>Correspondence:</bold> Kevin Y. Wu, Division of Ophthalmology, Department of Surgery, University of Sherbrooke, Sherbrooke, QC J1K2R1, Canada. <email>yang.wu@usherbrooke.ca</email></corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<pub-date pub-type="epub">
<day>28</day>
<month>11</month>
<year>2024</year>
</pub-date>
<volume>1</volume>
<issue>6</issue>
<fpage>300</fpage>
<lpage>330</lpage>
<history>
<date date-type="received">
<day>22</day>
<month>08</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>11</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2024.</copyright-statement>
<license xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.</license-p>
</license>
</permissions>
<abstract>
<p id="absp-1">The fusion of biomaterial science with clinical practice in oculoplastic and orbital surgery, particularly in the reconstruction of the posterior lamella of the eyelid, the lacrimal system, orbital floor fractures, and the development of implants for anophthalmic sockets, represents a frontier where materials meet surgical techniques. This review, which spans research from 2015 to 2023, delves into the application and integration of biopolymers and functional biomaterials in these complex areas. The discussion begins by reviewing the key anatomy of the external ocular surface, lacrimal system, and orbit. It then summarizes the various current surgical approaches for treating diseases affecting the external ocular surface and orbital involvement, with an emphasis on the associated challenges. The discussion continues with a comprehensive overview of the advantages and disadvantages of current and emerging biomaterials, including synthetic and natural polymers, used in reconstructive surgeries. These include applications for eyelid structure reconstruction, lacrimal system repair, orbital bone fracture repair, and orbital socket reconstruction. Throughout the review, the pathophysiology and challenges associated with these reconstructive procedures are explored, with an emphasis on surgical nuances and the ongoing pursuit of optimal reconstruction techniques. Finally, this review serves as a valuable resource for familiarizing clinicians with current knowledge and generating future hypotheses. It concludes that no evidence-based guidelines currently exist in oculoplastic surgery regarding the use of biopolymers in reconstructive procedures. Further research is needed to evaluate the efficacy and reproducibility of these biopolymers.</p>
</abstract>
<kwd-group>
<kwd>biopolymers</kwd>
<kwd>orbital implants</kwd>
<kwd>eyelid surgery</kwd>
<kwd>lacrimal system</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="s1">
<title>Introduction</title>
<p id="p-1">The field of oculoplastic surgery encompasses numerous surgical interventions that can be summarized into three fields: the orbit, the eyelids, and the lacrimal system. Eyelid reconstructions are amongst the most performed surgical interventions globally [<xref ref-type="bibr" rid="B1">1</xref>]. Oculoplastic surgical traumas are non negligeable; from 2006 to 2015 in the United States, 4.2 million emergency department visits were shown to be related to primary oculoplastic diagnosis, in which 70% were trauma-induced diagnosis, and nearly half of those cases required a surgical intervention [<xref ref-type="bibr" rid="B2">2</xref>]. Orbital floor fracture incidence was shown to have increased by nearly 50% from 2006 to 2017 in the United States [<xref ref-type="bibr" rid="B3">3</xref>]. The economic burden of eyelid laceration repair was shown to have further increased by nearly $30 million, accounting for approximately $1,600 per person in the United States [<xref ref-type="bibr" rid="B4">4</xref>]. Over the past years, efforts have been deployed to reduce the associated costs with surgical interventions. Current modern medicine, shifting its practice towards sustainable alternatives, has shed light in the past years on the use of polymer composites to leverage the economical, sustainable, and safety challenges, and further provide better patient care [<xref ref-type="bibr" rid="B5">5</xref>]. Current breakthroughs in medicine involve the use of polymer composites for orbital implants, posterior lamellar eyelid reconstructions, and as well as the lacrimal system [<xref ref-type="bibr" rid="B5">5</xref>–<xref ref-type="bibr" rid="B8">8</xref>]. In addition to being a great sustainable alternative to current surgical synthetic materials, polymer composites have shown high biocompatibility and low immunogenicity [<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B10">10</xref>]. The aim of this comprehensive literature review is to provide an overview of the most recent studies involving the use of polymer composites in the field of oculoplastic surgery. To better comprehend the challenges associated with current surgical techniques, the anatomy of the eyelid, lacrimal system, and orbits are first presented. Secondly, the most current surgical approaches for eyelid reconstruction surgeries, dacryocystorhinostomy (DCR), and orbital surgeries are discussed along with their respective challenges. Finally, this review discusses the most novel polymer composites in these surgical settings and proposes future perspectives regarding their possible role in a clinical setting.</p>
</sec>
<sec id="s2">
<title>The anatomy of the ocular external surface, lacrimal system, and orbit</title>
<sec id="t2-1">
<title>Eyelid and lacrimal system anatomy</title>
<p id="p-2">The eyelids and lacrimal system are crucial structures of the eye with various roles such as tear film distribution, tear drainage, protection of the ocular surface, and cosmesis [<xref ref-type="bibr" rid="B11">11</xref>]. The average dimension of the adult palpebral fissure varies from 28–30 mm horizontally and 10–12 mm vertically [<xref ref-type="bibr" rid="B12">12</xref>]. The eyelid is anatomically divided into two lamellae: the anterior and the posterior lamellae (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig id="fig1" position="float">
<label>Figure 1</label>
<caption>
<p id="fig1-p-1">
<bold>Schematic illustration of the eyelid structures.</bold> The eyelid structures encompass the conjunctiva, orbicularis oculi muscle, meibomian gland, tarsal plate, and lash follicle. Created in BioRender. Hocini, A. (2024) <ext-link xlink:href="https://biorender.com/z59t140" ext-link-type="uri">https://BioRender.com/z59t140</ext-link></p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ebmx-01-101322-g001.tif" />
</fig>
<p id="p-3">The anterior lamella of the eyelid is composed of very thin skin and the orbicularis oculi muscle. Given the extremely thin aspect of the eyelid’s skin, it is more flexible than surrounding skin, allowing for repetitive blinking movements [<xref ref-type="bibr" rid="B13">13</xref>]; unfortunately, this unique characteristic also poses significant challenges for skin grafts. Furthermore, although the eyelid skin is deprived of surface lipids, the presence of large superficial corneocytes (i.e., terminally differentiated keratinocytes) allows for adequate hydration [<xref ref-type="bibr" rid="B13">13</xref>]. The orbicularis oculi muscle beneath the skin is divided into the orbital and palpebral portions. The orbital portion of the orbicularis oculi muscle allows for tight eye closure. The medial portion of the orbicularis oculi muscle plays an important role in the lacrimal pump mechanism [<xref ref-type="bibr" rid="B14">14</xref>].</p>
<p id="p-4">The posterior lamella consists of the tarsus, the orbital septum, and the underlying conjunctiva. The tarsal plate is made up of dense connective tissue, encompassing type I, III, and IV collagen, chondroitin, and keratan sulfate [<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>], and serves as a structural support for the eyelids. The extracellular matrix of the tarsal plate consists of a collagen-elastin network and highly contributes to the biomechanics of the eyelid tarsus [<xref ref-type="bibr" rid="B16">16</xref>]. Finally, the meibomian glands are located within the tarsal plate and are vital for lipid layer synthesis in the tear film [<xref ref-type="bibr" rid="B17">17</xref>]. Post-secretion modifications and damages to the meibomian glands can alter the lipid components and synthesis capacity respectively, therefore destabilizing the tear film and leading to dry eye syndrome [<xref ref-type="bibr" rid="B17">17</xref>].</p>
<p id="p-5">Drainage of tears occurs through the lacrimal system. Pathologies involving the lacrimal system at different levels, such as nasolacrimal duct obstruction (NDO) and ectropion’s, can lead to disrupted tear film drainage. The lacrimal system encompasses the lacrimal gland, the punctums, the lacrimal sac, and the ducts and canals interconnecting the lacrimal system (<xref ref-type="fig" rid="fig2">Figure 2</xref>) [<xref ref-type="bibr" rid="B18">18</xref>].</p>
<fig id="fig2" position="float">
<label>Figure 2</label>
<caption>
<p id="fig2-p-1">
<bold>Schematic illustration of the lacrimal system.</bold> The lacrimal system structures consist of the following: lacrimal gland, lacrimal gland duct, upper punctum, superior lacrimal canal, lacrimal sac, lower punctum, and inferior lacrimal canal. Created in BioRender. Hocini, A. (2024) <ext-link xlink:href="https://biorender.com/o05x888" ext-link-type="uri">https://BioRender.com/o05x888</ext-link></p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ebmx-01-101322-g002.tif" />
</fig>
<p id="p-6">The main lacrimal gland can be divided into two lobes: the orbital lobe, which is twice as large as its other division, and the palpebral lobe [<xref ref-type="bibr" rid="B19">19</xref>]. The orbital lobe lies in the lacrimal fossa while the palpebral lobe lies under the levator palpebrae. The excretory ducts of the main lacrimal gland open into the superior conjunctival fornix. In the lamina propria of the conjunctiva, we can find the glans of Krause and the glans of Wolfring, two subdivisions of the accessory lacrimal glands. The ducts of the accessory lacrimal glands both open onto the conjunctiva surface [<xref ref-type="bibr" rid="B20">20</xref>]. The puncta are located near the medial canthi; they serve as the entry point for the lacrimal tears to be drained. Both canaliculi meet at the lacrimal sac. The valve of Rosenmüller is a mucosal flap that prevents tear reflux from the lacrimal sac to the canaliculi [<xref ref-type="bibr" rid="B21">21</xref>]. The lacrimal sac lies in the lacrimal sac fossa and runs down vertically to become the nasolacrimal duct. This duct then empties into the inferior nasal meatus. The valve of Hasner, found within the nasolacrimal duct, prevents retrograde displacement of tears originating from the nasal cavity [<xref ref-type="bibr" rid="B22">22</xref>].</p>
</sec>
<sec id="t2-2">
<title>Anatomy of the orbit</title>
<p id="p-7">Orbital injuries are often associated with major traumas, where motorcycle collisions account for most cases [<xref ref-type="bibr" rid="B23">23</xref>]. However, the mechanism of injury was shown to differ according to age groups and ethnicity [<xref ref-type="bibr" rid="B24">24</xref>]. Elderly people were shown to be more prone to have fall-induced orbital injuries, whereas Hispanic and African-American people were shown to have assault-related orbital injuries [<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B26">26</xref>]. Blow out fractures (i.e., fracture to one or more bones surrounding the eye) are the consequence of isolated facial blunt traumas [<xref ref-type="bibr" rid="B27">27</xref>]. The orbits are susceptible to injury given their complex anatomy involving soft tissues and 7 bones (<xref ref-type="fig" rid="fig3">Figure 3</xref>) [<xref ref-type="bibr" rid="B28">28</xref>].</p>
<fig id="fig3" position="float">
<label>Figure 3</label>
<caption>
<p id="fig3-p-1">
<bold>Anterior and lateral view of the human skull structures and orbit anatomy.</bold> Created in BioRender. Hocini, A. (2024) <ext-link xlink:href="https://biorender.com/u78q526" ext-link-type="uri">https://BioRender.com/u78q526</ext-link></p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ebmx-01-101322-g003.tif" />
</fig>
</sec>
</sec>
<sec id="s3">
<title>Current surgical approaches for ocular external surface diseases and orbital involvement and their challenges</title>
<sec id="t3-1">
<title>Ptosis repair</title>
<p id="p-8">The prevalence of ptosis was shown to range from 4.7% to 13.5% based on the study population [<xref ref-type="bibr" rid="B29">29</xref>]. The pathophysiology of ptosis encompasses a wide array of etiologies [<xref ref-type="bibr" rid="B30">30</xref>], such as aponeurotic ptosis [<xref ref-type="bibr" rid="B31">31</xref>], neurogenic ptosis [<xref ref-type="bibr" rid="B32">32</xref>], third cranial nerve palsy [<xref ref-type="bibr" rid="B33">33</xref>], Horner syndrome [<xref ref-type="bibr" rid="B34">34</xref>], myogenic ptosis [<xref ref-type="bibr" rid="B35">35</xref>], myasthenia gravis [<xref ref-type="bibr" rid="B36">36</xref>], chronic progressive external ophthalmoplegia [<xref ref-type="bibr" rid="B37">37</xref>], oculopharyngeal muscular dystrophy [<xref ref-type="bibr" rid="B38">38</xref>], and traumatic ptosis [<xref ref-type="bibr" rid="B39">39</xref>]. Surgery is an effective way to treat this condition and is indicated in cases of visual field abnormality secondary to ptosis or, in some cases, for aesthetic purposes [<xref ref-type="bibr" rid="B40">40</xref>]. Depending on the etiology of the ptosis, different surgical techniques can be used (<xref ref-type="table" rid="t1">Table 1</xref>). The levator aponeurosis advancement procedure consists of an incision through the eyelid skin, followed by dissection of the orbital septum to identify the dehisced or disinserted aponeurosis. The levator is then advanced and sutured to the upper one-third of the tarsus [<xref ref-type="bibr" rid="B41">41</xref>]. Conversely, the Muller’s muscle-conjunctival resection (MMCR) technique, involves everting the upper eyelid to expose the conjunctiva to subsequently resect the Muller’s muscle and excess tissue [<xref ref-type="bibr" rid="B42">42</xref>]. The frontalis flap is another surgical procedure to treat congenital or acquired ptosis, with the aim of elevating the frontalis muscle to the superior one third of the tarsus with sutures [<xref ref-type="bibr" rid="B43">43</xref>]. However, given that this technique is not reversible, it is not indicated in patients with poor levator function secondary to paralytic or myogenic causes, in which post-operative success is dependent upon reversibility and height adjustments [<xref ref-type="bibr" rid="B43">43</xref>]. Conversely to this technique, the frontalis sling method utilizes a sling material to elevate the frontalis muscle [<xref ref-type="bibr" rid="B44">44</xref>]. Different materials can be used to create the sling, with autogenous fascia considered the material of choice due to its lowest recurrence of ptosis and complications [<xref ref-type="bibr" rid="B45">45</xref>]. Other materials used include banked fascia [<xref ref-type="bibr" rid="B46">46</xref>], nylon monofilament [<xref ref-type="bibr" rid="B47">47</xref>], polyester [<xref ref-type="bibr" rid="B48">48</xref>], PTFE [<xref ref-type="bibr" rid="B47">47</xref>], polypropylene [<xref ref-type="bibr" rid="B49">49</xref>], ETHIBOND [<xref ref-type="bibr" rid="B50">50</xref>], and silicone [<xref ref-type="bibr" rid="B51">51</xref>]. Recurrence rates vary from one material to another, with PTFE and nylon monofilament yielding the highest complication and recurrence rates [<xref ref-type="bibr" rid="B47">47</xref>]. Furthermore, inflammatory reactions, such as mycobacterial infections [<xref ref-type="bibr" rid="B52">52</xref>] and orbital inflammation [<xref ref-type="bibr" rid="B53">53</xref>], can occur at the site of insertion of the material and have been shown to vary depending on material choice [<xref ref-type="bibr" rid="B54">54</xref>, <xref ref-type="bibr" rid="B55">55</xref>]. Overall, each current surgical technique for ptosis repair comes with disadvantages. There is therefore a crucial need to improve surgical techniques to provide better outcome long term.</p>
<table-wrap id="t1">
<label>Table 1</label>
<caption>
<p id="t1-p-1">
<bold>Key surgical approaches for ptosis repair</bold>
</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>
<bold>Surgical technique</bold>
</th>
<th>
<bold>Key features</bold> </th>
<th>
<bold>Advantages</bold>
</th>
<th>
<bold>Disadvantages</bold>
</th>
<th>
<bold>References</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<bold>Levator advancement</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>The levator aponeurosis is advanced and sutured to the superior tarsus</p>
</list-item>
<list-item>
<p>Mainly recommended for aponeurotic and involutional ptosis</p>
</list-item>
<list-item>
<p>No material needed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Small-incision techniques exist</p>
</list-item>
<list-item>
<p>Possibility of performing simultaneous blepharoplasty</p>
</list-item>
<list-item>
<p>Reoperation is easy to perform</p>
</list-item>
<list-item>
<p>Minimal changes in eyelid anatomy</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Does not correct dermatochalasis or lash ptosis</p>
</list-item>
<list-item>
<p>Recurrence rate between 9–12%</p>
</list-item>
<list-item>
<p>Entropion of the upper lid</p>
</list-item>
<list-item>
<p>Possibility of over- or under correction of the ptosis</p>
</list-item>
<list-item>
<p>Risk of asymmetry in upper eyelid height</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B30">30</xref>, <xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B56">56</xref>–<xref ref-type="bibr" rid="B61">61</xref>]</td>
</tr>
<tr>
<td>
<bold>Muller’s muscle-conjunctival resection (MMCR)</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Muller’s muscle and conjunctiva are excised after everting the upper eyelid</p>
</list-item>
<list-item>
<p>Mainly for mild to moderate ptosis with good LPS muscle function</p>
</list-item>
<list-item>
<p>No material needed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Less risk of injury to sensory nerves and the distal branch of the facial nerve</p>
</list-item>
<list-item>
<p>No visible scar</p>
</list-item>
<list-item>
<p>Short operating time and learning curve</p>
</list-item>
<list-item>
<p>Avoidance of dry eyes and floppy eyelid</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Need for an additional incision for blepharoplasty</p>
</list-item>
<list-item>
<p>Not indicated for poor levator function</p>
</list-item>
<list-item>
<p>May increase symptoms in patients with dry-eye syndrome</p>
</list-item>
<list-item>
<p>Avoided in patients with corneal disease or filtering blebs</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B61">61</xref>–<xref ref-type="bibr" rid="B63">63</xref>]</td>
</tr>
<tr>
<td>
<bold>Frontalis flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Consists of releasing the frontalis muscle and suturing it to the upper tarsus</p>
</list-item>
<list-item>
<p>No material needed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>No need for alloplastic or autologous tissue</p>
</list-item>
<list-item>
<p>Improves the direction of the pull</p>
</list-item>
<list-item>
<p>Minimal ptosis on upward gaze compared to frontalis sling</p>
</list-item>
<list-item>
<p>Can be done at a younger age</p>
</list-item>
<list-item>
<p>Low risk of facial nerve injury</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Possibility of severe lagophthalmos, lid lag, and nocturnal exposure keratopathy</p>
</list-item>
<list-item>
<p>Eyebrow asymmetry</p>
</list-item>
<list-item>
<p>Overcorrection not reversible</p>
</list-item>
<list-item>
<p>Not indicated in patients with poor levator function</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B64">64</xref>–<xref ref-type="bibr" rid="B66">66</xref>]</td>
</tr>
<tr>
<td>
<bold>Frontalis sling</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Linkage of the frontalis muscle to the eyelid tarsus using a sling material</p>
</list-item>
<list-item>
<p>Material of choice: autogenous fascia</p>
</list-item>
<list-item>
<p>Other materials used: banked fascia, nylon monofilament, polyester, PTFE, polypropylene, ETHIBOND, and silicone</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Better eyelid position in primary gaze</p>
</list-item>
<list-item>
<p>Possibility of reversibility if overcorrection</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Lagophtalmos</p>
</list-item>
<list-item>
<p>Eyelid lag in downgaze</p>
</list-item>
<list-item>
<p>Scarring and loss of eyelid crease</p>
</list-item>
<list-item>
<p>26% recurrence rate</p>
</list-item>
<list-item>
<p>Foreign body sensation</p>
</list-item>
<list-item>
<p>Granuloma or eyelid infections</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B44">44</xref>–<xref ref-type="bibr" rid="B51">51</xref>, <xref ref-type="bibr" rid="B67">67</xref>]</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="t3-2">
<title>Tumor excision</title>
<p id="p-9">Eyelid tumors can be benign, with multiple examples including papillomas [<xref ref-type="bibr" rid="B68">68</xref>], seborrheic keratosis, chalazion [<xref ref-type="bibr" rid="B69">69</xref>], nevus [<xref ref-type="bibr" rid="B70">70</xref>], or cysts [<xref ref-type="bibr" rid="B71">71</xref>]. Malignant tumors include basal cell carcinoma (BCC) [<xref ref-type="bibr" rid="B72">72</xref>], being the most common, squamous cell carcinoma (SCC) [<xref ref-type="bibr" rid="B73">73</xref>], sebaceous gland carcinoma [<xref ref-type="bibr" rid="B74">74</xref>], or Merkel cell carcinoma [<xref ref-type="bibr" rid="B75">75</xref>]. Surgical excision with tumor free margins is the gold standard to treat malignant tumors [<xref ref-type="bibr" rid="B76">76</xref>]. Ensuing surgical excision, multiple approaches can be used to repair the eyelid. An upper lid defect of up to 20% in young patients and 30% in older patients can be addressed with direct closure [<xref ref-type="bibr" rid="B77">77</xref>]. For larger eyelid defects, grafts can be used. An anterior lamellar defect can be reconstructed using a full-thickness skin graft using upper or lower eyelid skin, posterior auricular skin, preauricular skin, or supraclavicular skin [<xref ref-type="bibr" rid="B77">77</xref>]. Tarsoconjunctival grafts taken from healthy eyelids are the gold standard for posterior lamina reconstruction [<xref ref-type="bibr" rid="B78">78</xref>]. Other eyelid repair techniques include various types of flaps (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
<table-wrap id="t2">
<label>Table 2</label>
<caption>
<p id="t2-p-1">
<bold>Summary of eyelid reconstructive techniques following tumor excision</bold>
</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>
<bold>Surgical technique</bold>
</th>
<th>
<bold>Key features</bold>
</th>
<th>
<bold>Advantages</bold>
</th>
<th>
<bold>Disadvantages</bold>
</th>
<th>
<bold>References</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<bold>Autografts</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>For anterior lamellar defects: full-thickness skin graft from upper or lower eyelid, posterior auricular, preauricular, or supraclavicular skin</p>
</list-item>
<list-item>
<p>For posterior lamellar defects: palatal mucosa, auricular cartilage, and tarsoconjunctival grafts are the gold standard</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Resilience and high vascularization</p>
</list-item>
<list-item>
<p>Effective conjunctival replacements</p>
</list-item>
<list-item>
<p>Less immune response</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Corneal irritation due to absence of goblet cells and a rough surface</p>
</list-item>
<list-item>
<p>Lack of rigidity compared to a native tarsal plate</p>
</list-item>
<list-item>
<p>Painful and increased post-op healing period</p>
</list-item>
<list-item>
<p>Limited donor area availability</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B78">78</xref>, <xref ref-type="bibr" rid="B79">79</xref>]</td>
</tr>
<tr>
<td>
<bold>Cutler-Beard flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Full-thickness cutaneo-conjunctival lower eyelid bridge flap over the upper eyelid, separated a few weeks later</p>
</list-item>
<list-item>
<p>No material needed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Usable for most defects</p>
</list-item>
<list-item>
<p>Effective for large eyelid defects</p>
</list-item>
<list-item>
<p>Can be combined with a graft to promote greater stability</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Entropion</p>
</list-item>
<list-item>
<p>Lid margin irregularity</p>
</list-item>
<list-item>
<p>Eyelash loss</p>
</list-item>
<list-item>
<p>Bridge flap necrosis</p>
</list-item>
<list-item>
<p>Eyelid retraction</p>
</list-item>
<list-item>
<p>Eyesight problems for people with low visual acuity on the unoperated eye</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B80">80</xref>–<xref ref-type="bibr" rid="B84">84</xref>]</td>
</tr>
<tr>
<td>
<bold>Rotational rhomboid flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>A rhomboid-shaped defect is created, consisting of two triangles placed base to base</p>
</list-item>
<list-item>
<p>No material needed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Minimal complications</p>
</list-item>
<list-item>
<p>Useful in challenging medial canthal defect</p>
</list-item>
<list-item>
<p>Low traction on the skin</p>
</list-item>
<list-item>
<p>Flap can be rotated in multiple directions</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Stress unevenly distributed</p>
</list-item>
<list-item>
<p>Modification in canthal height</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B85">85</xref>–<xref ref-type="bibr" rid="B87">87</xref>]</td>
</tr>
<tr>
<td>
<bold>Mustardé rotational flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>First incision made at the lateral canthus all the way up at the level of the eyebrows</p>
</list-item>
<list-item>
<p>Second incision vertical to the tragus</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Minimal skin tension</p>
</list-item>
<list-item>
<p>Useful for large defects</p>
</list-item>
<list-item>
<p>Can be combined with a posterior lamellar graft</p>
</list-item>
<list-item>
<p>Good cosmetic result, low complication rate and low patient morbidity</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Downward contraction and sagging of the flap</p>
</list-item>
<list-item>
<p>Ectropion</p>
</list-item>
<list-item>
<p>Need of a septal cartilage mucoperichondrial autograft to reproduce the tarsus</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B88">88</xref>–<xref ref-type="bibr" rid="B90">90</xref>]</td>
</tr>
<tr>
<td>
<bold>Tripier flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Musculocutaneous bipedicle flap from the upper eyelid suspended at both canthi not including the tarsal plate</p>
</list-item>
<list-item>
<p>With or without septal cartilage graft</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Considered one of the best to repair lower-lid retraction or ectropion</p>
</list-item>
<list-item>
<p>Good aesthetic and functional results, with excellent color match</p>
</list-item>
<list-item>
<p>Low complication rate</p>
</list-item>
<list-item>
<p>Less damage to the facial nerve</p>
</list-item>
<list-item>
<p>Preserve the continuity of orbicularis muscle fibers</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Ectropion</p>
</list-item>
<list-item>
<p>Epiphora</p>
</list-item>
<list-item>
<p>Eyelid edema</p>
</list-item>
<list-item>
<p>Lagophthalmos</p>
</list-item>
<list-item>
<p>Dry eyes</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B91">91</xref>, <xref ref-type="bibr" rid="B92">92</xref>]</td>
</tr>
<tr>
<td>
<bold>Hughes tarsoconjunctival flap</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Tarsoconjunctival flap from upper eyelid, split at the mucocutaneous junction and attached to the lower lid conjunctiva</p>
</list-item>
<list-item>
<p>Flap is Separated few weeks later</p>
</list-item>
<list-item>
<p>With or without a skin graft</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Best used for full-thickness defects of the central portion of the lower lid</p>
</list-item>
<list-item>
<p>Good functional and aesthetic results</p>
</list-item>
<list-item>
<p>Low complication rate</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Lower lid margin erythema</p>
</list-item>
<list-item>
<p>Lower lid ectropion or entropion</p>
</list-item>
<list-item>
<p>Lagophthalmos</p>
</list-item>
<list-item>
<p>Infection or flap dehiscence</p>
</list-item>
<list-item>
<p>Eyelid retraction</p>
</list-item>
<list-item>
<p>Dry eyes</p>
</list-item>
<list-item>
<p>Corneal abrasion</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B93">93</xref>–<xref ref-type="bibr" rid="B95">95</xref>]</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="t3-3">
<title>Cutler-Beard technique</title>
<p id="p-10">The bridging flap, also known as the Cutler-Beard technique, is a surgical approach primarily used to repair large defects in the eyelid, in cases such as the resection of a sebaceous gland carcinoma [<xref ref-type="bibr" rid="B80">80</xref>]. This intervention requires the placement of a full-thickness cutaneo-conjunctival lower eyelid bridge flap over the upper eyelid after tumor excision [<xref ref-type="bibr" rid="B81">81</xref>]. The bridge is then separated a few weeks after the surgery [<xref ref-type="bibr" rid="B82">82</xref>]. Unfortunately, multiple limitations and complications are associated with this specific technique, such as the lack of upper eyelid lashes post-reconstruction, vision impairment prior to bridge separation, necrosis of the flap, lower eyelid ectropion, cicatricial ectropion, and upper eyelid retraction [<xref ref-type="bibr" rid="B96">96</xref>]. Additionally, the pressure from the bridging skin flap can cause erosion or damage to the cornea. Finally, dehiscence of the graft can occur due to the application of opposite forces by the upper and lower eyelids.</p>
</sec>
<sec id="t3-4">
<title>Rotational rhomboid flap</title>
<p id="p-11">The rotational rhomboid flap can be useful to repair eyelid defects, especially in the medial canthus area [<xref ref-type="bibr" rid="B85">85</xref>]. A rhomboid shape defect is created with the virtual long axis, in which the flap can be rotated in multiple directions to cover the defect [<xref ref-type="bibr" rid="B86">86</xref>]. The challenge with this technique is ensuring that the stress on the skin is well distributed and no modification of the canthal height is made [<xref ref-type="bibr" rid="B86">86</xref>].</p>
</sec>
<sec id="t3-5">
<title>Mustardé rotational flap</title>
<p id="p-12">The Mustardé rotational flap, along with the bridging flap, can also be used for large defects following a tumor excision [<xref ref-type="bibr" rid="B89">89</xref>]. In this procedure, a septal cartilage mucoperichondrial autograft is used to reproduce the tarsal plate [<xref ref-type="bibr" rid="B88">88</xref>, <xref ref-type="bibr" rid="B89">89</xref>]. The Mustardé flap yields very good cosmetic outcomes because it preserves the texture and skin color of the patient, while ensuring adequate vascularization to the operated area [<xref ref-type="bibr" rid="B97">97</xref>]. However, the most common post-operative complication of this intervention is sagging of the lower eyelid and ectropion [<xref ref-type="bibr" rid="B88">88</xref>, <xref ref-type="bibr" rid="B89">89</xref>].</p>
</sec>
<sec id="t3-6">
<title>Tripier flap</title>
<p id="p-13">The Tripier flap can be to correct an ectropion after another reconstruction surgery like the Mustardé flap or the V-Y advanced flap [<xref ref-type="bibr" rid="B91">91</xref>]. It can also be a good option for correcting full-thickness eyelid defects. The preservation of muscle fibers within the flap provides for excellent tissue vascularization and aesthetic results. This surgery also tends to cause less damage to the facial nerve and keep the integrity of the orbicularis muscle fibers. Other variations of the Tripier flap can be utilized to reconstruct the upper eyelid or even the use of single-pedicle flap [<xref ref-type="bibr" rid="B92">92</xref>]. However, since the procedure relies on the properties of existing tissue on the patient, flap size is limited to the amount of excess skin available.</p>
</sec>
<sec id="t3-7">
<title>Hughes tarsoconjunctival flap</title>
<p id="p-14">The Hughes tarsoconjunctival flap involves the creation of a tarsoconjunctival flap from the ipsilateral upper eyelid. Given the two-stage nature of the procedure, it poses similar limitations as mentioned earlier with the Cutler-Beard flap. Furthermore, a careful dissection of the levator muscle from the tarsoconjunctival flap needs to be done to avoid eyelid retraction. Other minor post-operative complications include flap necrosis, corneal abrasion on flap division, mucous discharge, or dry eye syndrome [<xref ref-type="bibr" rid="B93">93</xref>, <xref ref-type="bibr" rid="B94">94</xref>].</p>
</sec>
<sec id="t3-8">
<title>Lacrimal system impairment</title>
<p id="p-15">DCR is one of the most common surgeries and is indicated when there is an NDO, that being either congenital or acquired. This obstruction can happen anywhere along the path of the lacrimal duct. DCR involves inserting a silicone tube into the punctum through the canaliculus to reinforce lacrimal drainage. However, it is to be noted that the tubes can be made of different material sources [<xref ref-type="bibr" rid="B98">98</xref>]. Silicone stents are currently the most commonly used. However, to reduce the high cost and the risk of infection of silicone stenting, Baruah et al. [<xref ref-type="bibr" rid="B99">99</xref>] studied the use of polypropylene stenting. Polypropylene is cheaper, readily available, shows less tissue reaction, and reduces bacterial contamination [<xref ref-type="bibr" rid="B99">99</xref>]. This material is also non absorbable and shows good tensile strength [<xref ref-type="bibr" rid="B99">99</xref>], therefore providing a great alternative to silicone stenting. External DCR has been thought to be the gold standard in DCR surgeries given the limited technology available for an endoscopic approach [<xref ref-type="bibr" rid="B100">100</xref>]. However, with recent advances in technology, endoscopic DCR has shown great success rates and is currently the preferred approach by most surgeons [<xref ref-type="bibr" rid="B101">101</xref>]. External DCR describes higher risk of bleeding and wound infection [<xref ref-type="bibr" rid="B102">102</xref>]. Endoscopic DCR is beneficial for multiple reasons, such as minimal invasiveness, preservation of the lacrimal pump function, shorter surgical duration, and better cosmetic outcome [<xref ref-type="bibr" rid="B102">102</xref>].</p>
</sec>
</sec>
<sec id="s4">
<title>Orbital involvement</title>
<sec id="t4-1">
<title>Orbital bone fracture</title>
<p id="p-16">Orbital floor fractures are amongst the most common site of injuries [<xref ref-type="bibr" rid="B103">103</xref>]. Data analysis from 2006 to 2017 has shown that the incidence of orbital floor fractures in the United States had significantly increased [<xref ref-type="bibr" rid="B3">3</xref>]. The primary goal in orbital fracture management is to maintain function and limit further damage on the globe. The majority of patients will benefit from a conservative approach [<xref ref-type="bibr" rid="B104">104</xref>]. However, in cases where surgery is necessary, this must be performed within 14 days of injury [<xref ref-type="bibr" rid="B104">104</xref>]. The indications for surgery are based on the clinical presentation. The presence of diplopia, enophthalmos (i.e., eye sinking deeper in the eye socket), and ocular motility dysfunctions are criteria for surgery [<xref ref-type="bibr" rid="B104">104</xref>]. Additional criteria based on orbital cavity volume and size of the fault area are considered [<xref ref-type="bibr" rid="B105">105</xref>]. Taken together, these clinical findings may be suggestive of a muscle entrapment.</p>
<p id="p-17">Three main factors should be considered in orbital fracture management: the surgical timeframe (i.e., within two weeks), the surgical approach, and the choice of material for the reconstruction. The surgical approaches for orbital floor repair can be divided into two approaches: the transcutaneous (i.e., subciliary, subtarsal, and infraorbital) or transconjunctival approach [<xref ref-type="bibr" rid="B106">106</xref>, <xref ref-type="bibr" rid="B107">107</xref>]. The transconjunctival approach is the preferred surgical method for orbital floor fracture repairs. The site of injury is accessed through an incision at the fornix of conjunctiva [<xref ref-type="bibr" rid="B106">106</xref>]. However, in many cases, a canthotomy is required to increase exposure rate, and is thus associated with a potential visible scar [<xref ref-type="bibr" rid="B108">108</xref>]. The subciliary approach consists on accessing the orbital floor through an incision at the lower lid [<xref ref-type="bibr" rid="B106">106</xref>]. One limitation of subciliary approach is its association with higher incidence of denervation of the pretarsal orbicularis [<xref ref-type="bibr" rid="B109">109</xref>]. In the subtarsal approach, the orbital floor is accessed through an incision below the eyelid margin in the subtarsal crease and extends laterally. This approach is preferred in comparison to the subciliary approach, given that it preserves the innervation of the tarsus [<xref ref-type="bibr" rid="B110">110</xref>]. The infraorbital approach’s advantage is a rapid and direct access to the orbital floor through an incision of the skin, orbicularis muscle, and periosteum [<xref ref-type="bibr" rid="B106">106</xref>].</p>
<p id="p-18">Aside from surgical timeframe and approach choice, the third and final consideration for orbital floor fractures regards material choice for the reconstruction. A variety of materials have been discussed in the literature for this purpose [<xref ref-type="bibr" rid="B111">111</xref>]. Unfortunately, there is still controversies in which material is better in orbital fracture reconstruction. Current biomaterials can be categorized into several types. These include biological materials like bone grafts, cartilage and fascia; metals like titanium and cobalt alloys; polymers, that can be porous or non-porous and either absorbable or not absorbable; biological ceramics, like porous hydroxyapatite (HA); and composites, like titanium reenforce polyethylene (PE) to name one (<xref ref-type="table" rid="t3">Table 3</xref>) [<xref ref-type="bibr" rid="B112">112</xref>]. For many years, autologous bone transplants for orbital floor fracture repairs used to be considered as the gold standard [<xref ref-type="bibr" rid="B113">113</xref>]. Autologous bone transplant is achieved by harvesting a bone sample from a donor site, consisting of either the mandibular coronoid process, anterior maxillary wall, mandibular symphysis, rib, or scapula, and using it as a rigid support during the reconstructive surgery [<xref ref-type="bibr" rid="B114">114</xref>–<xref ref-type="bibr" rid="B117">117</xref>]. However, given the increased donor site morbidity, variability in resorption rates, and technical difficulty, treatment paradigm has shifted towards the use of allogenic and mainly alloplastic materials [<xref ref-type="bibr" rid="B113">113</xref>, <xref ref-type="bibr" rid="B118">118</xref>]. Allogenic materials in oculoplastic surgery refers to tissues harvested from another individual for surgical purposes, whereas alloplastic materials are from a synthetic origin. The most common alloplastic material in maxillofacial surgery is titanium. Titanium osteosynthesis biomaterials are currently the gold standard in maxillofacial fracture managements [<xref ref-type="bibr" rid="B119">119</xref>]. Nevertheless, multiple challenges are also associated with the use of this biomaterial; titanium systems are challenging given the potential restriction in bone growth, sensitivity to temperature, mutagenicity, tactical discomfort associated with the plates and screws, and interference with radiological imaging techniques [<xref ref-type="bibr" rid="B120">120</xref>–<xref ref-type="bibr" rid="B122">122</xref>]. To leverage the challenges associated with these systems, numerous efforts have been deployed in the past years to develop high standard biopolymers for orbital floor fracture management. In the ensuing sections, we delve into the most recent and novel applications for orbital floor fracture repair, as well as their involvement in orbital bioimplants. However, with the recent advances in the use of biopolymers in medicine, a shift in the clinical interest towards these materials for orbital floor fracture management has been observed. Novel advances in this field will be further discussed in the subsequent sections.</p>
<table-wrap id="t3">
<label>Table 3</label>
<caption>
<p id="t3-p-1">
<bold>Summary of current materials used in orbital bone fracture repair</bold>
</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>
<bold>Material type</bold>
</th>
<th>
<bold>Advantages</bold>
</th>
<th>
<bold>Disadvantages</bold>
</th>
<th>
<bold>References</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<bold>Bone grafts</bold>
<break />(Calvarium, iliac crest, rib, maxillary sinus)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Cost-effective</p>
</list-item>
<list-item>
<p>Good stability</p>
</list-item>
<list-item>
<p>Maximal biocompatibility</p>
</list-item>
<list-item>
<p>Smooth surface</p>
</list-item>
<list-item>
<p>Variability in thickness</p>
</list-item>
<list-item>
<p>Radio-opacity</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Limited availability</p>
</list-item>
<list-item>
<p>Variable resorption rate (unpredictable orbit volume)</p>
</list-item>
<list-item>
<p>Donor site morbidity</p>
</list-item>
<list-item>
<p>Increased surgical time</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B123">123</xref>–<xref ref-type="bibr" rid="B127">127</xref>]</td>
</tr>
<tr>
<td>
<bold>Titanium meshes</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Permanent and good fixation</p>
</list-item>
<list-item>
<p>Good compatibility and permeability</p>
</list-item>
<list-item>
<p>Good strength</p>
</list-item>
<list-item>
<p>Radio-opacity</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Risk of late infections secondary to chronic sinusitis</p>
</list-item>
<list-item>
<p>Expensive</p>
</list-item>
<list-item>
<p>Not easily removable</p>
</list-item>
<list-item>
<p>Sharp edges and palpable</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B123">123</xref>–<xref ref-type="bibr" rid="B126">126</xref>, <xref ref-type="bibr" rid="B128">128</xref>–<xref ref-type="bibr" rid="B130">130</xref>]</td>
</tr>
<tr>
<td>
<bold>Porous polyethylene sheets</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Allows for tissue integration</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Lack of rigidity</p>
</list-item>
<list-item>
<p>Not visible on imaging</p>
</list-item>
<list-item>
<p>High cost</p>
</list-item>
<list-item>
<p>Risk of compartment syndrome</p>
</list-item>
<list-item>
<p>Less drainage</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B123">123</xref>–<xref ref-type="bibr" rid="B126">126</xref>, <xref ref-type="bibr" rid="B129">129</xref>, <xref ref-type="bibr" rid="B131">131</xref>, <xref ref-type="bibr" rid="B132">132</xref>]</td>
</tr>
<tr>
<td>
<bold>Composite of porous polyethylene and titanium meshes</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Combines advantages from both biomaterial</p>
</list-item>
<list-item>
<p>Radio-opacity</p>
</list-item>
<list-item>
<p>Good stability and fixation</p>
</list-item>
<list-item>
<p>Can be used in three-wall fractures</p>
</list-item>
<list-item>
<p>Allows for tissue integration</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Risk of compartment syndrome</p>
</list-item>
<list-item>
<p>High cost</p>
</list-item>
<list-item>
<p>No need for donor site</p>
</list-item>
<list-item>
<p>Less drainage</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B124">124</xref>–<xref ref-type="bibr" rid="B126">126</xref>, <xref ref-type="bibr" rid="B128">128</xref>–<xref ref-type="bibr" rid="B130">130</xref>, <xref ref-type="bibr" rid="B132">132</xref>]</td>
</tr>
<tr>
<td>
<bold>Resorbable materials</bold>
<break />(thermoplastic and non-thermoplastics)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Good availability</p>
</list-item>
<list-item>
<p>Smooth surface</p>
</list-item>
<list-item>
<p>Good malleability (thermoplastics only)</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Not visible on imaging</p>
</list-item>
<list-item>
<p>Possibility of material degradation</p>
</list-item>
<list-item>
<p>Inflammatory response</p>
</list-item>
<list-item>
<p>Less drainage</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B123">123</xref>–<xref ref-type="bibr" rid="B126">126</xref>, <xref ref-type="bibr" rid="B129">129</xref>, <xref ref-type="bibr" rid="B132">132</xref>]</td>
</tr>
<tr>
<td>
<bold>Preformed orbital implant</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Smooth surface</p>
</list-item>
<list-item>
<p>Minimal countering needed</p>
</list-item>
<list-item>
<p>Radio-opacity</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Very high cost</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B112">112</xref>, <xref ref-type="bibr" rid="B123">123</xref>–<xref ref-type="bibr" rid="B126">126</xref>, <xref ref-type="bibr" rid="B129">129</xref>, <xref ref-type="bibr" rid="B132">132</xref>]</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="t4-2">
<title>Globe rupture</title>
<p id="p-19">In more severe cases involving damage to the eye globe, enucleation or exenteration can be performed. Both of these surgeries may be indicated in various scenarios that create a painful eye, such as trauma to the eye with loss of its content, endophthalmitis with phthisis, and keratoconjunctivitis complicated by globe perforation. These surgeries are also indicated to prevent the progression of an existing eye neoplasia [<xref ref-type="bibr" rid="B133">133</xref>].</p>
<p id="p-20">Orbital exenteration is a radical and disfiguring surgical technique that involves the removal the entire orbital content and the surrounding structures, such as the muscles, fat, nerves and in some cases the eyelid [<xref ref-type="bibr" rid="B134">134</xref>]. In contrast, enucleation consists of the removal of the entire eye globe, but preserves the surrounding structures [<xref ref-type="bibr" rid="B135">135</xref>].</p>
<p id="p-21">Once the globe is removed, an orbital implant needs to be inserted for aesthetic purposes and to restore eye volume. Multiple implants are currently being used, but controversies still exist concerning the best choice of implants (<xref ref-type="table" rid="t4">Table 4</xref>). The most common materials that are currently used are ceramics, autologous materials, silicone, PMMA, porous PE, and poly-HEMA [<xref ref-type="bibr" rid="B133">133</xref>]. Although numerous choices are available, these materials encompass various disadvantages such high cost, implant-associated infections, impediment on fibrovascular growth, fistula creation, delayed healing, and tumor recurrence [<xref ref-type="bibr" rid="B136">136</xref>].</p>
<table-wrap id="t4">
<label>Table 4</label>
<caption>
<p id="t4-p-1">
<bold>Summary of current used materials for orbital socket implants</bold>
</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th>
<bold>Material type</bold>
</th>
<th>
<bold>Advantages</bold>
</th>
<th>
<bold>Disadvantages</bold>
</th>
<th>
<bold>References</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<bold>Ceramics</bold>
<break />(hydroxyapatite)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Allows tissue ingrowth</p>
</list-item>
<list-item>
<p>Well tolerated</p>
</list-item>
<list-item>
<p>Provides good motility</p>
</list-item>
<list-item>
<p>Few complications</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Can cause conjunctival abrasion</p>
</list-item>
<list-item>
<p>Not recommended for pediatric patients</p>
</list-item>
<list-item>
<p>High cost</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>, <xref ref-type="bibr" rid="B137">137</xref>–<xref ref-type="bibr" rid="B142">142</xref>]</td>
</tr>
<tr>
<td>
<bold>Autologous materials</bold>
<break />(Bone, fat, skin, cartilage, muscle)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Cheaper alternative</p>
</list-item>
<list-item>
<p>Preferred in pediatric patients</p>
</list-item>
<list-item>
<p>Used to wrap exposed implants</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Unpredictable graft uptake</p>
</list-item>
<list-item>
<p>Requires additional surgery</p>
</list-item>
<list-item>
<p>Risk of post-operative complications</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>–<xref ref-type="bibr" rid="B135">135</xref>, <xref ref-type="bibr" rid="B143">143</xref>]</td>
</tr>
<tr>
<td>
<bold>Silicone</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Inertness</p>
</list-item>
<list-item>
<p>Biocompatible</p>
</list-item>
<list-item>
<p>Relatively good pliability</p>
</list-item>
<list-item>
<p>Used to produce spherical non-orbital implant</p>
</list-item>
<list-item>
<p>Low complication rate</p>
</list-item>
<list-item>
<p>Non-porous silicone preferred in children because it is easily removable</p>
</list-item>
<list-item>
<p>Easily surgically placed</p>
</list-item>
<list-item>
<p>Allows tissue ingrowth</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Typical foreign body reaction with the formation of a dense avascular capsule around the implant</p>
</list-item>
<list-item>
<p>Fibrovascular ingrowth is not possible</p>
</list-item>
<list-item>
<p>Exposure often leads to implant removal, and is less treatable conservatively</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>, <xref ref-type="bibr" rid="B143">143</xref>, <xref ref-type="bibr" rid="B144">144</xref>]</td>
</tr>
<tr>
<td>
<bold>Poly(methylmethacrylate) (PMMA)</bold>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Excellent biocompatibility</p>
</list-item>
<list-item>
<p>Widely used to fabricate intraocular lenses, orbital implants and rigid contact lenses</p>
</list-item>
<list-item>
<p>Low cost</p>
</list-item>
<list-item>
<p>Good clinical outcomes</p>
</list-item>
<list-item>
<p>Easily surgically placed</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Fibrovascular ingrowth is not possible</p>
</list-item>
<list-item>
<p>Exposure often leads to implant removal, and is less treatable conservatively</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>, <xref ref-type="bibr" rid="B143">143</xref>, <xref ref-type="bibr" rid="B145">145</xref>–<xref ref-type="bibr" rid="B148">148</xref>]</td>
</tr>
<tr>
<td>
<bold>Porous PE (polyethylene)</bold>
<break />(Medpor)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Allows tissue ingrowth</p>
</list-item>
<list-item>
<p>Low-cost alternative to other implants</p>
</list-item>
<list-item>
<p>Soft surface and well tolerated by soft tissue</p>
</list-item>
<list-item>
<p>Reduced risk of complications</p>
</list-item>
<list-item>
<p>Pliable</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Not recommended for pediatric patients</p>
</list-item>
<list-item>
<p>Slower vascularization compared to other materials</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>, <xref ref-type="bibr" rid="B143">143</xref>, <xref ref-type="bibr" rid="B146">146</xref>, <xref ref-type="bibr" rid="B149">149</xref>]</td>
</tr>
<tr>
<td>
<bold>Poly-HEMA (2-hydroxyethyl methacralate)</bold>
<break />(Alphasphere)</td>
<td>
<list list-type="bullet">
<list-item>
<p>Does not require tissue wrapping</p>
</list-item>
<list-item>
<p>Muscle can be sutured directly to the implant</p>
</list-item>
<list-item>
<p>Smooth surface</p>
</list-item>
<list-item>
<p>Limit risk of exposure</p>
</list-item>
<list-item>
<p>Allows tissue ingrowth</p>
</list-item>
</list>
</td>
<td>
<list list-type="bullet">
<list-item>
<p>Implant disintegration</p>
</list-item>
<list-item>
<p>Fragmentation</p>
</list-item>
<list-item>
<p>Partial extrusion</p>
</list-item>
<list-item>
<p>Host reaction</p>
</list-item>
</list>
</td>
<td>[<xref ref-type="bibr" rid="B133">133</xref>, <xref ref-type="bibr" rid="B143">143</xref>, <xref ref-type="bibr" rid="B146">146</xref>, <xref ref-type="bibr" rid="B150">150</xref>]</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="t4-3">
<title>Overview of polymer composites</title>
<p id="p-22">In the following sections, a comprehensive review of polymer composites will be presented. Due to some disadvantages highlighted among the various materials previously reviewed in this paper, polymer composites in medicine have experienced rapid growth in recent years. These new polymers are particularly significant and deserve attention, as they have been proposed as innovative alternatives for biomedical applications, including drug delivery, tissue engineering and regeneration, medical devices, and implants [<xref ref-type="bibr" rid="B151">151</xref>]. Their biocompatibility with human tissues, non-toxic nature, and their sustainable alternative have rendered biopolymers as an essential tool for modern medicine [<xref ref-type="bibr" rid="B152">152</xref>]. Polymer composites can be classified into different categories based on the classification system. They can be categorized based on their nature (biodegradable or non-biodegradable), their composition (i.e., based on the main material), their type (natural or synthetic) or their dimension. Novel classification systems favor a bi-parameter classification, outlining the type and nature of polymer composites (<xref ref-type="fig" rid="fig4">Figure 4</xref>). The biochemical properties of these biopolymers have been thoroughly reviewed, therefore they will not be covered in depth in this section [<xref ref-type="bibr" rid="B153">153</xref>].</p>
<fig id="fig4" position="float">
<label>Figure 4</label>
<caption>
<p id="fig4-p-1">
<bold>General classification of polymer composites</bold>
</p>
</caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ebmx-01-101322-g004.tif" />
</fig>
<p id="p-23">Natural non-biodegradable polymer composites, such as bio-polyethylene terephthalate (PET), bio-PE, bio-polyamide (PA), and bio-poly(trimethylene terephthalate), are a great alternative to current synthetic sutures given their greater sustainability and environment friendly features. Furthermore, being biological products (i.e., plant-based or animal-based materials), they exhibit greater compatibility. However, current knowledge regarding their application in the field of oculoplastic surgery is sparse. In the past years, efforts have been deployed to develop natural non-biodegradable polymer composites in the field of manufacturing, for packaging and engineering (i.e., medical devices) [<xref ref-type="bibr" rid="B154">154</xref>]. However, advances in the field of oculoplastics are limited to none. Therefore, this comprehensive literature review will cover the application of the other three categories of polymer composites in the field of oculoplastic surgery. However, to be able to use these materials in reconstructive surgeries, they need to encompass certain general characteristics; the optimal polymer composite should be resorbable, biodegradable, resistant to infection, minimally reactive, cost effective, easy to manipulate, and easily accessible [<xref ref-type="bibr" rid="B155">155</xref>]. When used in the setting of an orbital floor fracture repair, they should in addition be osteoconductive, not induce capsule formation, and possess a half-life long enough to favor bone growth [<xref ref-type="bibr" rid="B155">155</xref>].</p>
</sec>
</sec>
<sec id="s5">
<title>Novel applications of polymer composites in oculoplastic surgery</title>
<sec id="t5-1">
<title>Materials for blepharoplasty and suturing</title>
<sec id="t5-1-1">
<title>Natural polymer composites</title>
<p id="p-24">Sutures are of great importance in reconstructive oculoplastic surgery. The tensile strength, biocompatibility and thermal stability are key features when engineering a suture. Furthermore, given the incidence of infection with blepharoplasty (0.2%) [<xref ref-type="bibr" rid="B156">156</xref>], the possibility to engineer a polymer composite with lower post-operative complication rates is highly sought after. Furthermore, biodegradable sutures are of interest given their greater esthetic outcome in eyelid reconstructive surgeries. The first approved natural polymer composite for suturing is the polyhydroxyalkanoate (PHA)-based suture from TephaFLEX [<xref ref-type="bibr" rid="B157">157</xref>], which was shown to induce no adverse effects one year post intramuscular implantation of the PHA-based sutures in animal models [<xref ref-type="bibr" rid="B158">158</xref>]. Since, numerous efforts have been deployed in developing new suture alternatives based on polymer composites for modern medicine [<xref ref-type="bibr" rid="B159">159</xref>]. Recently, de la Harpe et al. [<xref ref-type="bibr" rid="B160">160</xref>] have proceeded with the engineering of a monofilament bioabsorbable suture composed of gelatin, sodium alginate, pectin and glycerol, that has drug delivery capabilities. They showed great biocompatibility of the suture with no cytotoxicity, as well as sustained drug delivery for 7 days [<xref ref-type="bibr" rid="B160">160</xref>]. The suture was successfully biodegraded within 28 days [<xref ref-type="bibr" rid="B160">160</xref>]. Similarly, Liu et al. [<xref ref-type="bibr" rid="B161">161</xref>] have shown the potential of polylactic acid (PLA) sutures loaded with microspheres enclosed drugs to delivery drugs post-surgically in a sustained manner, while maintaining the optimal mechanical properties [<xref ref-type="bibr" rid="B161">161</xref>].</p>
<p id="p-25">Collagen and chitosan-based polymer composites have also shown great potential as suture alternatives. Collagen nanofibrils (CoNF) confer great mechanical stability. CoNF were shown to promote tendon-derived cell proliferation in vitro [<xref ref-type="bibr" rid="B162">162</xref>]. In fact, wound healing is highly dependent on cell proliferation at the surgical site. Conversely, chitosan-coated silk sutures have also shown great antibacterial efficacy [<xref ref-type="bibr" rid="B163">163</xref>, <xref ref-type="bibr" rid="B164">164</xref>], mainly against <italic>Staphylococcus epidermis</italic> and <italic>Candida albicans</italic> [<xref ref-type="bibr" rid="B165">165</xref>]. Although these results were obtained in fields not involving reconstructive eyelid surgeries, the same outcomes can be hypothesized. However, further studies in the field of oculoplastic are needed to better understands the visual and clinical outcomes of natural polymer composites as alternatives to standard sutures.</p>
</sec>
<sec id="t5-1-2">
<title>Synthetic polymer composites</title>
<p id="p-26">Non-biodegradable sutures are of interest in oculoplastic surgery for specific applications, such as tarsorrhaphy’s (i.e., procedure consisting of approximating the upper and lower eyelid in conditions with corneal exposure, such as chronic lagophthalmos). Clinical efficacity of PE sutures have been demonstrated on numerous occasions [<xref ref-type="bibr" rid="B166">166</xref>]; PE is amongst the most studied polymer composites for various biomedical applications [<xref ref-type="bibr" rid="B167">167</xref>, <xref ref-type="bibr" rid="B168">168</xref>]. However, a major challenge regarding their use concerns their long-term safety and biodegradation.</p>
</sec>
</sec>
<sec id="t5-2">
<title>Materials for lacrimal system stenting</title>
<sec id="t5-2-1">
<title>Natural polymer composites</title>
<p id="p-27">Selvam et al. [<xref ref-type="bibr" rid="B169">169</xref>] compared the utilization of various polymers to support the morphological and physiological characteristics of rabbit purified lacrimal gland acinar (PLGA) cells for the development of a novel treatment for dry eye syndrome. They compared the efficacy of collagen 1, silicone, poly-<italic>D</italic>,<italic>L</italic>-lactide-<italic>co</italic>-glycolide, Thermanox<sup>®</sup>, and poly-<italic>L</italic>-lactic acid (PLLA), and concluded that PLLA was the most effective biopolymer among the others in supporting the growth of PLGA [<xref ref-type="bibr" rid="B169">169</xref>]. In 2009, the same authors continued their research and developed a microporous PLLA membrane (mPLLAm) to enhance scaffold properties for lacrimal acinar cells by aiming for improved permeability. The results were very promising and suggested that this biomaterial could be a promising avenue for the development a bioartificial lacrimal gland device [<xref ref-type="bibr" rid="B170">170</xref>]. A recent study created a decellularized lacrimal gland-derived hydrogel and compared its capacity to promote proliferation of porcine lacrimal gland epithelial cells to other biomaterials like Matrigel and collagen-1 [<xref ref-type="bibr" rid="B171">171</xref>]. After 24 h of hydrolyzing, the decellularized hydrogel led to better epithelial growth and functionality compared to other materials [<xref ref-type="bibr" rid="B171">171</xref>]. This in vitro experiment could potentially pave the way for the next generation of lacrimal gland engineering devices. In 2017, Hsiao et al. [<xref ref-type="bibr" rid="B172">172</xref>] decided to approach pathologies of the lacrimal glands with another angle; instead of finding a way to replace the gland, they decided to use a chitosan biomaterial to create a biocompatible environment to promote and mimic the branching structure formation of the lacrimal gland. The biomaterial works by increasing affinity of the lacrimal gland for hepatocyte growth factor (HGF), which is beneficial for the branching morphogenesis and structural development [<xref ref-type="bibr" rid="B172">172</xref>]. Hsiao et al. [<xref ref-type="bibr" rid="B173">173</xref>] also highlighted one of the main limitations of chitosan, which was the elimination of the polymer functionality after using certain pathway inhibitors such as PD98059 and LY2944002, inhibiting the MAPK and Akt/PKB pathways respectively [<xref ref-type="bibr" rid="B173">173</xref>]. Even though little research on this polymer exists, these two projects led by Hsiao et al. [<xref ref-type="bibr" rid="B173">173</xref>] could be the starting point for a new use of biopolymers in lacrimal gland regeneration.</p>
</sec>
<sec id="t5-2-2">
<title>Synthetic polymer composites</title>
<p id="p-28">Pinilla et al. [<xref ref-type="bibr" rid="B174">174</xref>] conducted a non-randomized prospective clinical trial to evaluate the effectiveness of fluoroscope-guided nasolacrimal stents of polyurethane on 86 patients with obstructive epiphora. Of the successfully placed stents, 40 (52.6%) were clinically successful, meaning they achieved resolution or net improvement of the symptoms [<xref ref-type="bibr" rid="B174">174</xref>]. Mild complications like epistaxis, palpebral hematoma, pain, or other less common complications were encountered in 19 eyes, and 33 stents became occluded after 24 months [<xref ref-type="bibr" rid="B174">174</xref>]. The study concluded that this technique was a good alternative for DCR, but yielded fewer effective results than the surgery itself [<xref ref-type="bibr" rid="B174">174</xref>]. Conversely, Baruah et al. [<xref ref-type="bibr" rid="B99">99</xref>] studied 51 cases of dacryocystitis and evaluated the effectiveness of polypropylene for stenting after DCR. The surgery was successful for 92.2% of the patients, which is comparable to the results of other studies [<xref ref-type="bibr" rid="B175">175</xref>–<xref ref-type="bibr" rid="B178">178</xref>]. The principal advantage of this polymer is its possibility to be a great alternative to silicone stents, considering its good efficacy and lower cost [<xref ref-type="bibr" rid="B99">99</xref>]. A study involving 91 patients even stated no significant differences between the success rate of silicone and polypropylene stenting for endoscopic DCR [<xref ref-type="bibr" rid="B179">179</xref>]. An important element to consider is the lack of consensus in the literature regarding the real efficacy of silicone stents [<xref ref-type="bibr" rid="B180">180</xref>–<xref ref-type="bibr" rid="B182">182</xref>]. Silicone stenting, when used for the treatment of epiphora, has been reported to have certain disadvantages such as its risk of bacterial infection, its poor efficacy due to its hydrophobic nature, or the surgical challenge associated with this stent due of the curved shape of the lacrimal duct [<xref ref-type="bibr" rid="B183">183</xref>]. The study conducted by Park et al. [<xref ref-type="bibr" rid="B183">183</xref>] tried to seek solutions to address these disadvantages of silicone stenting. After experimenting with different materials, they synthesized a shape memory polymer (SMP) with elastic proprieties that allowed self-expansion, made of 94% polycaprolactone (PCL)-6%PGMA [<xref ref-type="bibr" rid="B183">183</xref>]. This polymer demonstrated excellent biocompatibility, improved efficacy in tear drainage, and superior resistance to bacteria compared to the conventional silicone stent, suggesting that it could be a better alternative [<xref ref-type="bibr" rid="B183">183</xref>]. Dai et al. [<xref ref-type="bibr" rid="B184">184</xref>] created an in situ degradable lacrimal plug made of methacrylate-modified silk fibroin (SFMA) which serves as a network with indocyanine green fluorescence tracer nanoparticle (FTN) [<xref ref-type="bibr" rid="B184">184</xref>]. In vivo testing on rabbits with dry eyes demonstrated that this trackable lacrimal duct plug could be a very good approach for the treatment of this condition in the future, considering the net improvement of symptoms with better lacrimal fluid retention and no inflammatory response [<xref ref-type="bibr" rid="B184">184</xref>]. In 2011, Chaloupka et al. [<xref ref-type="bibr" rid="B185">185</xref>] described a promising solution to resolve the frequent complication of duct blockage or displacement associated with the implantation of rigid Lester Jones tubes for tear duct surgery. They created a conduit made from polyhedral oligomeric silsesquioxane-poly(carbonate-urea) urethane (POSS-PCU) and demonstrated its superiority to its predecessors by demonstrating its improved biocompatibility, structure, and functional abilities [<xref ref-type="bibr" rid="B185">185</xref>].</p>
</sec>
</sec>
<sec id="t5-3">
<title>Grafts</title>
<sec id="t5-3-1">
<title>Natural polymer composites</title>
<p id="p-29">One of the biggest challenges in eyelid surgery is finding an adequate replacement material for the tarsus. Although, autografts and acellular dermal matrices (ADMs) are potential polymer composites for eyelid reconstruction surgeries, they have limitations; autografts may carry iatrogenic risks, and ADMs can cause infections and immunologic responses [<xref ref-type="bibr" rid="B186">186</xref>]. ADMs consist of connective tissue matrix—a collagen matrix—that does not exhibit immunogenic properties [<xref ref-type="bibr" rid="B187">187</xref>]. ADMs possess several beneficial properties that make them a suitable choice for eyelid reconstruction surgery. They provide rapid and long-term adherence to the wound surface, resistance to mechanical stress, and elastic properties making it able to adapt to ocular contours; other benefits of ADMs include the absence of antigenicity and toxicity, cost-efficiency, and extended shelf life as compared to other alternatives [<xref ref-type="bibr" rid="B188">188</xref>]. In a study involving 20 patients who underwent eyelid tumor resections, Ma et al. [<xref ref-type="bibr" rid="B189">189</xref>] explored the use of ADMs for eyelid reconstruction. They utilized ADMs as a substitute for the tarsal plate and the conjunctivae post-tumor resection. The study concluded that ADMs could be an effective alternative for posterior lamellar material. The results were promising: pedicle flaps survived in 90% of the patients, no tumor recurrence was noted, visual acuity and ocular movement were preserved in all patients, and half of the patients achieved excellent aesthetic results [<xref ref-type="bibr" rid="B189">189</xref>]. In addition to the long surviving time period, the authors mention that this polymer composite can assure stability of the eyelid, exhibit a good biocompatibility, and reduce complications related to the donor site [<xref ref-type="bibr" rid="B15">15</xref>]. Another study involving 21 patients also focused on reconstructive eyelid surgery following tumor resections [<xref ref-type="bibr" rid="B190">190</xref>]. It concluded that xenogeneic acellular dermal matrix shows encouraging results as a biomaterial for future tarsal plate replacement procedures [<xref ref-type="bibr" rid="B190">190</xref>]. Barmettler et al. [<xref ref-type="bibr" rid="B191">191</xref>] pursued a prospective randomized clinical trial in 2018 to compare the outcomes of the reparation of eyelid retraction using three different graft types: autologous auricular cartilage, bovine ADM, and porcine ADM [<xref ref-type="bibr" rid="B191">191</xref>]. The results showed significantly increased postoperative swelling in the auricular cartilage group compared to the other alternatives [<xref ref-type="bibr" rid="B191">191</xref>]. Although no other statistically significant differences in overall outcomes were observed among the three groups, the auricular cartilage grafts exhibited a higher inflammatory response. This finding suggests that clinicians may need to consider other criteria before using them and might prefer ADMs in order to avoid additional surgical sites and reduce surgical time [<xref ref-type="bibr" rid="B191">191</xref>]. Additionally, the absence of conjunctival surface with auricular grafts in ADM could potentially increase patient comfort.</p>
<p id="p-30">Conversely, to imitate the eyelid tarsus, Sun et al. [<xref ref-type="bibr" rid="B192">192</xref>] applied fibroblasts, previously cultured from human eyelids, on chitosan hydrogel scaffolds. Using immunocytochemical staining, they demonstrated the scaffold’s ability to support and promote the growth and proliferation of human fibroblasts [<xref ref-type="bibr" rid="B192">192</xref>]. This innovation could potentially be a big step in the field of eyelid reconstruction, giving a personalized and biocompatible replacement to the tarsus. Another study by Drechsler et al. [<xref ref-type="bibr" rid="B193">193</xref>] investigated the use of compressed collagen for replacing the epithelial conjunctiva in fornix reconstruction surgeries. They found that this biopolymer had excellent strength and elasticity, but was also as malleable as the amniotic membrane (AM) [<xref ref-type="bibr" rid="B193">193</xref>], therefore providing promising avenues for this biopolymer for future advancements in conjunctival surgeries. Xu et al. [<xref ref-type="bibr" rid="B186">186</xref>] combined collagen and chitosan (COL/CS) to create a biphasic scaffold, and further integrated a COL/CS sponge with a poly(propylene fumarate)-<italic>co</italic>-2-hydroxyethyl methacrylate (PPF-HEMA) polymer network [<xref ref-type="bibr" rid="B186">186</xref>]. The PPF-HEMA layer acts as a structural base, while the COL/CS sponge retains water and imitates the conjunctival layer. This results in reduced inflammation and improved cell infiltration and proliferation [<xref ref-type="bibr" rid="B186">186</xref>]. We think that this multi-biomaterial approach could then be a great way for creating advanced scaffolds in eyelid surgery, using the unique key points of each biopolymer to compensate for the limitations of others.</p>
<p id="p-31">Over the past years, the AM has proven to be very effective and useful in various pathologies and situations such as socket contracture, cicatricial disorders like Stevens-Johnson syndrome [<xref ref-type="bibr" rid="B194">194</xref>], cryptophthalmos [<xref ref-type="bibr" rid="B195">195</xref>], conjunctivochalasis [<xref ref-type="bibr" rid="B196">196</xref>], and even as an adjuvant in skin grafts [<xref ref-type="bibr" rid="B197">197</xref>]. In 2017, Singh et al. [<xref ref-type="bibr" rid="B197">197</xref>] reported a case involving a 20-year-old woman with a junctional eyelid kissing nevus. Like other studies on the subject [<xref ref-type="bibr" rid="B198">198</xref>–<xref ref-type="bibr" rid="B200">200</xref>], the combination of skin grafts and AM grafting (AMG) led to very good functional and cosmetic outcomes. Rahal et al. [<xref ref-type="bibr" rid="B198">198</xref>] studied the midterm results following resection of ocular surface squamous neoplasia of the fornix. The surgical repair technique used a mucosal graft combined with AMG. Among the 83 eyes from the 76 patients in the study, only 23 (27.71%) underwent successful corrective surgery, partially explained by secondary complications such as symblepharon, cicatricial ectropion, pannus, and corneal decompensation [<xref ref-type="bibr" rid="B198">198</xref>]. This study concluded that this technique preserved the vision, anatomy, and function of the eye confirming the efficacy of this surgical procedure [<xref ref-type="bibr" rid="B198">198</xref>]. In another case report, Reed et al. [<xref ref-type="bibr" rid="B201">201</xref>] described a 20-year-old male who underwent surgery for a right upper eyelid laceration following a car accident. They utilized a combination of a skin graft and AMG, which yielded good cosmetic results; the authors went onto highlighting the importance of the AM which acts as a scaffold for the healthy surrounding skin to proliferate [<xref ref-type="bibr" rid="B201">201</xref>]. This novel technique proved to be advantageous for multiple reasons: It avoids contracture of the surrounding tissue and reduces the need for large skin graft, which is beneficial for extensive lesions where skin availability is limited. The procedure can also be done without sedation, it can be very useful in settings where an operating room is not available. Finally, the low risk of scarring makes it a technique of choice because it can occur with many other management techniques.</p>
<p id="p-32">A case report by Borrelli et al. [<xref ref-type="bibr" rid="B202">202</xref>] described the management of a 49-year-old woman with an adenoid cystic carcinoma in the pterygopalatine fossa who underwent multiple radiotherapy and surgical treatments. The patient developed lagophthalmos due to seventh nerve palsy and lead to exposure keratopathy because of cornea exposure post-operatively. Due to the lack of healthy skin for autologous grafts, a decellularized porcine-derived membrane (tarSys) was selected to treat the lower lid retraction. Three months after the surgery, no lagophthalmos or symptoms of keratopathy were present, however, the long-term outcomes of the procedure were not reported. In 2013, a retrospective study was conducted by Liao et al. [<xref ref-type="bibr" rid="B203">203</xref>] to evaluate the efficacy of tarSys for the treatment of lower lid retraction in patients with graves ophthalmopathy. This study, which included 37 eyelids, concluded that tarSys was a good alternative for eyelid grafts. Another case report was published on a 54-year-old woman who underwent bilateral lower eyelid surgery using a porcine decellularized membrane graft [<xref ref-type="bibr" rid="B204">204</xref>]. Due to unilateral eye pain months after the procedure, the graft was removed after 15 months [<xref ref-type="bibr" rid="B204">204</xref>]. Pathological analysis revealed an inflammatory response, demonstrating that a host reaction can occur even in the theorical absence of antigens. Given that the literature on the use of decellularized grafts in humans is perhaps limited, these biopolymers should only be used as a second line of treatment or when other materials are unavailable or contraindicated.</p>
</sec>
<sec id="t5-3-2">
<title>Synthetic polymer composites</title>
<p id="p-33">In 2004, Tan et al. [<xref ref-type="bibr" rid="B205">205</xref>] studied the use of porous PE lower eyelid spacers (Medpor LES) for the management of different causes of eyelid retraction. A Medpor LES was utilized in 32 patients for a total of 35 eyelids and the study results demonstrated a statistically significant clinical improvement 22 months post-surgery and a decrease of the following complications: palpebral aperture, lagophthalmos, increased L-MRD, and LSS [<xref ref-type="bibr" rid="B205">205</xref>]. However, other significant complications were reported in seven patients, consisting of implant exposure and reduced eye mobility, ultimately leading to the removal of the implant [<xref ref-type="bibr" rid="B205">205</xref>]. Eight patients also encountered minor complications requiring further surgical intervention such as transient lash loss, skin contour abnormalities, or margin ectropion. Although, the procedure yielded adequate results for 24 eyelids, 28% of the cases had satisfactory or poor outcomes. Due to the high number of complications and the frequent need for reoperation, this technique should be considered only when autologous grafts are not possible. The main advantage of this technique is to reduce surgical time and can be very useful for patients lacking skin to graft [<xref ref-type="bibr" rid="B206">206</xref>].</p>
<p id="p-34">Xu et al. [<xref ref-type="bibr" rid="B207">207</xref>] further analyzed the potential of branched porous polyethylene for eyelid reconstruction, which offers a superior alternative for soft tissue replacement. They mainly focused on the elasticity properties of branched porous polyethylene with the aim of mimicking the eyelid’s tarsus. The study resulted in promising results. During subcutaneous implantation in rats, they observed a very mild inflammatory response, along with collagen deposition and fibro-vascularization [<xref ref-type="bibr" rid="B207">207</xref>]. Their trial on rabbits, demonstrated that the polyethylene had the same elasticity and repair properties of Medpor transplants used in the control group [<xref ref-type="bibr" rid="B207">207</xref>]. It also resulted in fewer eyelid deformities and a higher degree of fibrovascular tissue formation than the Medpor transplants [<xref ref-type="bibr" rid="B207">207</xref>]. This suggests that porous polyethylene could be a better option for in vivo eyelid reconstruction, particularly because of its non-toxic properties, addressing potential concerns about its use. However, to the best of the author’s knowledge, no trials involving human eyelid have been done. Poly(3-hydroxybutyrate-<italic>co</italic>-3-hydroxyhexanoate) (PHBHHx) is another synthetic polymer used in reconstruction of the eyelid. Zhou et al. [<xref ref-type="bibr" rid="B208">208</xref>] explored the use of PHBHHx as a substitute for the tarsus in comparison to ADMs. They found that both polymers were effective materials used for eyelid repair. Histological analysis two weeks post-implantation in rats revealed inflammation in this group, despite PHBHHx demonstrating good biocompatibility and elasticity [<xref ref-type="bibr" rid="B208">208</xref>]. Such findings could indicate that alternative polymers with lower inflammatory responses might be preferable. Other studies have also explored the employment of PCL for conjunctival reconstructions [<xref ref-type="bibr" rid="B209">209</xref>] or for tarsal reconstruction [<xref ref-type="bibr" rid="B210">210</xref>].</p>
</sec>
</sec>
<sec id="t5-4">
<title>Mesh for orbital bone fractures</title>
<sec id="t5-4-1">
<title>Natural polymer composites</title>
<p id="p-35">Natural biopolymers (i.e., biomaterials derived from nature) that have demonstrated their efficiency and safety in orbital injury repairs mainly encompass gelatin film. Gelatin films have been used for over two decades in oculoplastic surgery. Derived from denatured collagen, gelatin films are efficient for the reconstruction of small orbital defects (&lt; 5 mm), whereas in larger defects, it can be used to bridge two distinctive materials such as plates and meshes [<xref ref-type="bibr" rid="B211">211</xref>]. When compared to silicone rubber, gelatin films were shown to decrease the migration of implants, relieve the post-surgical inflammatory processes, and contribute to a better healing outcome [<xref ref-type="bibr" rid="B212">212</xref>]. Although natural biopolymers have excellent biocompatibility and biodegradability, few challenges exist with the use of natural biopolymers, such as limited availability and great complexity associated with its extraction and synthesis. Synthetic biopolymers can overcome these challenges and are advantageous for many reasons, such as their tunable properties and consistent structure [<xref ref-type="bibr" rid="B213">213</xref>].</p>
<p id="p-36">The use of protein-based coatings on synthetic biopolymers have recently been contributing to the paradigm shift in reconstructive maxillo-facial surgeries, including orbital floor fracture injuries. Recombinant bone morphogenic protein (BMP) can be coated onto numerous biopolymers, where its addition was shown to favor osteointegration of synthetic biopolymers through material integration and surface charge modulations [<xref ref-type="bibr" rid="B214">214</xref>, <xref ref-type="bibr" rid="B215">215</xref>]. Four types of biopolymer coatings can be employed: transforming growth factor (TGF) β, BMP-2, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF) [<xref ref-type="bibr" rid="B216">216</xref>]. However, studies regarding their use in orbital injuries are limited.</p>
<p id="p-37">BMP-2 coating is mainly used for its strong osteoconductive power [<xref ref-type="bibr" rid="B216">216</xref>]. Its use in orthopedic surgeries is well known [<xref ref-type="bibr" rid="B217">217</xref>], however, studies encompassing orbital injuries are limited. Using polylacticglycolide acid copolymer coated with BMP-2 in a sheep model with an orbital floor fracture, Zheng et al. [<xref ref-type="bibr" rid="B218">218</xref>] have demonstrated the efficacity of the biomaterial in reconstructive surgery; upon absorption of the coated biopolymer, the defect was filled with a complex tissue (i.e., bone tissue, connective tissue, and mucosal epithelial layers), representative of the normal environment [<xref ref-type="bibr" rid="B218">218</xref>]. The use of additives and coatings is currently in emergence and additional studies along this topic are to be expected within the next years.</p>
</sec>
<sec id="t5-4-2">
<title>Synthetic polymer composites</title>
<p id="p-38">The use of poly(methyl methacrylate) (PMMA) in blowout orbital fractures has recently been emphasized [<xref ref-type="bibr" rid="B148">148</xref>, <xref ref-type="bibr" rid="B219">219</xref>]. Moldable PMMA was shown to be safe and effective in two patients with orbital blowout fractures [<xref ref-type="bibr" rid="B219">219</xref>].</p>
</sec>
</sec>
<sec id="t5-5">
<title>Orbital socket implants</title>
<sec id="t5-5-1">
<title>Semi-synthetic polymer composites</title>
<p id="p-39">Silicone has been used for decades in reconstructive surgeries for its cost-effectiveness, adherence capacity, enhanced permeability, and thermal and chemical stability [<xref ref-type="bibr" rid="B220">220</xref>–<xref ref-type="bibr" rid="B222">222</xref>]. However, given the significant implant-related complications, such as implant extrusion, socket edema, implant migration, and mechanical obstruction, current clinical practice has shifted away from the use of silicone implants [<xref ref-type="bibr" rid="B223">223</xref>, <xref ref-type="bibr" rid="B224">224</xref>]. Semi-synthetic biopolymers have gained interest within the last five years given their similarity to the bone structure, their ability to effectively reconstruct orbital floor fractures, and the ability of mass production for these compounds.</p>
<p id="p-40">HA compounds are known as ceramic materials and are mainly composed of calcium and phosphate ions, which confers its highly biocompatible and non-toxic properties [<xref ref-type="bibr" rid="B225">225</xref>]. However, challenges regarding the porosity, density, and composition of HA limits their use in single-based biomaterials [<xref ref-type="bibr" rid="B226">226</xref>]. HA-derived biopolymers’ efficacity in orbital floor and wall reconstruction surgeries has been demonstrated in conjunction with PLLA and PCL [<xref ref-type="bibr" rid="B227">227</xref>–<xref ref-type="bibr" rid="B229">229</xref>]. A recent retrospective study showed similar safety and efficiency of unsintered HA (uHA)/PLLA in comparison to PCL mesh for orbital wall fracture reconstructions [<xref ref-type="bibr" rid="B228">228</xref>]. However, one recent study has reported the presence of postoperative diplopia and enophthalmos in 12 patients who underwent orbital wall fracture repair with uHA/PLLA [<xref ref-type="bibr" rid="B230">230</xref>]. This outcome was reported to be induced by the extent and severity of the fracture. The Hess area ratio (HAR) is an objective and quantitative tool to measure eye movements and has shown great utility in assessing the post-surgical outcome in patients with orbital blowout fractures [<xref ref-type="bibr" rid="B227">227</xref>, <xref ref-type="bibr" rid="B231">231</xref>]. When compared to silicone sheets or a combination of sheets, no significant differences in postoperative HAR was obtained with uHA/PLLA, suggesting that uHA/PLLA biopolymers are as effective as conventional materials for orbital floor fracture reconstruction [<xref ref-type="bibr" rid="B227">227</xref>].</p>
</sec>
<sec id="t5-5-2">
<title>Synthetic polymer composites</title>
<p id="p-41">A study investigating the efficacity of PMMA implants in patients who underwent enucleation secondary to retinoblastoma’s demonstrated very little complications; implant migration was noted in only 28 (9%) patients and implant exposure and contracted socked was reported in 5 (2%) patients for each outcome [<xref ref-type="bibr" rid="B220">220</xref>]. These recent contributions to the novelty of PMMA implants and biopolymers are along the same findings reported nearly two decades ago [<xref ref-type="bibr" rid="B147">147</xref>].</p>
<p id="p-42">Porous PE-Medpor-usage is not exclusive to eyelid reconstructive surgeries; the successful usage of Medpor as implants has also been showing great results [<xref ref-type="bibr" rid="B232">232</xref>–<xref ref-type="bibr" rid="B236">236</xref>]. In a recent 6-month follow-up study published this year, porous PE implants were shown to be associated with nearly absent complications: 1 patient (6%) exhibited implant migration, whereas 93% of participants reported a satisfactory outcome [<xref ref-type="bibr" rid="B234">234</xref>]. However, given that non-negligeable infection and implant exposure and distortion long-term complications have been reported with porous PE, the clinical decision to use these biopolymers in certain patients should be made with precaution [<xref ref-type="bibr" rid="B237">237</xref>–<xref ref-type="bibr" rid="B239">239</xref>].</p>
</sec>
</sec>
</sec>
<sec id="s6">
<title>Future directions in biomaterials research</title>
<p id="p-43">A substantial amount of work has already been conducted on the study of these biomaterials, as reviewed in this paper. The authors have identified several gaps in the current literature and aim to highlight these areas to encourage further studies. It would be valuable to conduct further studies on the various drugs used in different eyelid and orbital surgeries, with a focus on their interactions with these new biomaterials. Studies employing numerical modeling approaches, such as the Finite Element Method or Multiphysics approach, would be highly beneficial for testing and evaluating differences of those biomaterials in the specific context of oculoplastic surgeries.</p>
</sec>
<sec id="s7">
<title>Conclusions</title>
<p id="p-44">Since the first discoveries in biopolymers for orbital implants and reconstructive surgeries, numerous advances and challenges attributed to autologous graft transplants have been conquered [<xref ref-type="bibr" rid="B240">240</xref>]. The realm of the current practice is fulfilled with a variety of biomaterials and a challenge regarding the choice of surgical implants and grafts for reconstructive surgery exists. Novel advances have shifted their paradigm towards the development of biocompatible, effective, non-toxic, cost-effective, and sustainable biopolymers for reconstructive eyelid, lacrimal, and orbital surgeries. Although numerous preclinical studies have underlined the efficiency of these biomaterials, no scientific-based recommendations in oculoplastic exist regarding the use of biopolymers in reconstructive surgeries. Further studies and meta-analyses are required to outline the efficiency and reproducibility of these biopolymers. Nevertheless, this review bridges the clinical knowledge regarding the surgical approaches in oculoplastic surgery with the fundamental sciences behind the development of novel biopolymers. It not only serves as a tool for clinicians to familiarize with the current knowledge but also guides research hypothesis within the field given the raised challenges throughout the comprehensive literature review.</p>
</sec>
</body>
<back>
<glossary>
<title>Abbreviations</title>
<def-list>
<def-item>
<term>ADMs</term>
<def>
<p>acellular dermal matrices</p>
</def>
</def-item>
<def-item>
<term>AM</term>
<def>
<p>amniotic membrane</p>
</def>
</def-item>
<def-item>
<term>AMG</term>
<def>
<p>amniotic membrane grafting</p>
</def>
</def-item>
<def-item>
<term>BMP</term>
<def>
<p>bone morphogenic protein</p>
</def>
</def-item>
<def-item>
<term>COL/CS</term>
<def>
<p>collagen and chitosan</p>
</def>
</def-item>
<def-item>
<term>CoNF</term>
<def>
<p>collagen nanofibrils</p>
</def>
</def-item>
<def-item>
<term>DCR</term>
<def>
<p>dacryocystorhinostomy</p>
</def>
</def-item>
<def-item>
<term>HA</term>
<def>
<p>hydroxyapatite</p>
</def>
</def-item>
<def-item>
<term>HAR</term>
<def>
<p>Hess area ratio</p>
</def>
</def-item>
<def-item>
<term>NDO</term>
<def>
<p>nasolacrimal duct obstruction</p>
</def>
</def-item>
<def-item>
<term>PCL</term>
<def>
<p>polycaprolactone</p>
</def>
</def-item>
<def-item>
<term>PE</term>
<def>
<p>polyethylene</p>
</def>
</def-item>
<def-item>
<term>PHA</term>
<def>
<p>polyhydroxyalkanoate</p>
</def>
</def-item>
<def-item>
<term>PHBHHx</term>
<def>
<p>poly(3-hydroxybutyrate-<italic>co</italic>-3-hydroxyhexanoate)</p>
</def>
</def-item>
<def-item>
<term>PLGA</term>
<def>
<p>purified lacrimal gland acinar</p>
</def>
</def-item>
<def-item>
<term>PLLA</term>
<def>
<p>poly-<italic>L</italic>-lactic acid</p>
</def>
</def-item>
<def-item>
<term>PMMA</term>
<def>
<p>poly(methyl methacrylate)</p>
</def>
</def-item>
<def-item>
<term>PPF-HEMA</term>
<def>
<p>poly(propylene fumarate)-<italic>co</italic>-2-hydroxyethyl methacrylate</p>
</def>
</def-item>
<def-item>
<term>uHA</term>
<def>
<p>unsintered HA</p>
</def>
</def-item>
</def-list>
</glossary>
<sec id="s8">
<title>Declarations</title>
<sec id="t-8-1">
<title>Author contributions</title>
<p>MK: Visualization, Project administration, Writing—original draft, Writing—review &amp; editing. KYW: Conceptualization, Writing—review &amp; editing. AH: Visualization, Writing—original draft, Writing—review &amp; editing. PD: Supervision, Writing—review &amp; editing. All authors read and approved the submitted version.</p>
</sec>
<sec id="t-8-2" sec-type="COI-statement">
<title>Conflicts of interest</title>
<p>The authors declare that they have no conflicts of interest.</p>
</sec>
<sec id="t-8-3">
<title>Ethical approval</title>
<p>Not applicable.</p>
</sec>
<sec id="t-8-4">
<title>Consent to participate</title>
<p>Not applicable.</p>
</sec>
<sec id="t-8-5">
<title>Consent to publication</title>
<p>Not applicable.</p>
</sec>
<sec id="t-8-6" sec-type="data-availability">
<title>Availability of data and materials</title>
<p>Not applicable.</p>
</sec>
<sec id="t-8-7">
<title>Funding</title>
<p>Not applicable.</p>
</sec>
<sec id="t-8-8">
<title>Copyright</title>
<p>© The Author(s) 2024.</p>
</sec>
</sec>
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