From:  Injectable biodegradable hydrogels for in situ tissue engineering

 Critical limitations and challenges in tissue-specific applications of injectable hydrogels.

Tissue applicationCritical weaknesses and limitationsKey references
CartilagePoor long-term mechanical durability under cyclic loading; inadequate recapitulation of zonal cartilage architecture (superficial, middle, deep zones); risk of fibrocartilage formation rather than hyaline cartilage; limited vascularization impairs nutrient delivery to encapsulated cells[28–30]
BoneInsufficient vascularization of large defects leading to core necrosis; mismatch between hydrogel degradation rate and bone remodeling timeline;potential immune reactions and fibrous encapsulation at the defect site; difficulty in achieving load-bearing mechanical strength comparable to native cortical bone[31–33, 43]
CardiacLow cell retention and survival in hostile post-MI environment; risk of arrhythmia induction by conductive fillers; mechanical mismatch with beating myocardium; challenge of achieving electromechanical integration with host tissue[2, 10, 17, 22]
NeuralRisk of glial scar formation and foreign body response; difficulty in guiding long-distance axonal regeneration across lesion site; potential neurotoxicity of conductive nanomaterials; mechanical mismatch with extremely soft neural tissue (E ~0.1–1 kPa)[2, 10, 27, 35]
SkinSusceptibility to bacterial colonization and biofilm formation in chronic wounds; excessive exudate absorption leading to hydrogel swelling and mechanical weakening; uneven vascularization in full-thickness defects; risk of hypertrophic scarring[21, 26, 36, 40]
DentalHostile oral microbiome and contamination risk; inadequate mechanical strength under masticatory loads; long-term degradation under cyclic wet-dry and thermal oral environment; limited clinical evidence beyond Phase I trials[9, 21, 31]
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