Exploration of BioMat-X

Table 4. Key biomaterial types and their roles in ECM mimicry.

Biomaterial category	Specific examples	Key properties (biocompatibility, degradability, mechanical tunability, cell adhesion motifs)	Contribution to ECM mimicry (compositional, structural, mechanical, biochemical cues)	Advantages of in vitro models	Associated challenges
Natural polymers	Collagen, fibrin, hyaluronic acid (HA), gelatin, alginate, chitosan, silk fibroin	High biocompatibility [83], low immunogenicity [84], inherent cell adhesion sites (e.g., RGD) [67], enzymatic degradability [66].	Compositional: mimic native ECM proteins/polysaccharides [63]. Structural: form hydrogels, fibrous networks [64]. Biochemical: present cell-binding motifs, sequester growth factors [76].	Excellent biological relevance, support cell growth/differentiation, tunable properties [66].	Variable batch-to-batch consistency, potential for immunogenicity (though low) [84], limited mechanical strength for some [85].
Synthetic polymers	Polyethylene glycol (PEG), polyisocyanide (PIC), polyacrylamide (PAAm), polyvinyl alcohol (PVA)	High tunability in physical/chemical properties, controllable degradation, low immunogenicity, resistance to non-specific protein adsorption [68, 69].	Structural: precise control over architecture, porosity. Mechanical: tunable stiffness/elasticity [73]. Biochemical: functionalizable with specific cues [30].	Greater control over properties, reduced variability, avoids animal-derived components, can be stimuli-responsive [79].	Often lack intrinsic bioactivity/cell adhesion, may require functionalization, potential cytotoxicity from residues [86].
Composite (semi-synthetic) biomaterials	Gelatin methacryloyl (GelMA), HA-PEG composites	Combines bioactivity of natural polymers with tunability/stability of synthetics; photopolymerizable, customizable mechanical properties [62, 87].	Comprehensive mimicry (compositional, structural, mechanical, biochemical) by integrating the best features of both categories [88].	Broad range of adjustable properties, enhanced physiological relevance, improved printability for bioprinting [89].	Balancing properties can be complex, potential for residual toxicity from crosslinking agents, regulatory hurdles for novel combinations [70].
Bioinks (specialized for 3D bioprinting)	GelMA, HAMA, alginate, recombinant spider silk proteins, cell aggregates	Tunable rheological properties (shear-thinning) [90], rapid gelation post-printing, biocompatibility, cell encapsulation capability [78].	Enables precise spatial patterning of cells and ECM components, vascularized channels, biochemical gradients, tissue-mimetic stiffness [77, 91].	Allows for complex, high-resolution 3D tissue constructs, high reproducibility, scalability for HTS [77].	Cytotoxicity due to UV light/free radicals (for photopolymerizable), oxygen inhibition, long printing times, need for more relevant ECM mimics [78].

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During the preparation of this work, the authors used Napkin AI for creating the Figures and QuillBot for improving language clarity and grammar. No AI tools were used for scientific writing, data analysis, or interpretation. After using these tools, the authors thoroughly reviewed and edited all content and take full responsibility for the integrity and accuracy of the publication.

Author contributions

SC: Conceptualization, Writing—original draft, Visualization. AD: Methodology, Writing—original draft, Visualization. AS: Methodology, Writing—original draft. PZ: Writing—review & editing. NG: Writing—review & editing. RS: Writing—review & editing. VT: Writing—review & editing. LMA: Writing—review & editing, Supervision. DG: Conceptualization, Writing—review & editing, Supervision. All authors have read and approved the submitted version.

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