Efficacy of decellularized meniscus xenogeneic substitutes from sheep and camels compared to human menisci

Abstract Meniscal damage treatment is challenging due to limited healing potential. Decellularized scaffolds offer tissue engineering potential, but their efficacy depends on maintaining extracellular matrix structure, host integration, biocompatibility, and minimizing immune response. This study aims to compare decellularized menisci from humans, sheep, and camels for regenerative applications. Three decellularized menisci underwent rigorous decellularization, assessed through DNA and glycosaminoglycan quantification, histological examination, scanning electron microscopy, mechanical moduli, degradation kinetics, biocompatibility, cytotoxicity, fibroblast proliferation potential, immunogenicity assays, and Raman confocal spectroscopy for scaffold constitutions. Histological and DNA analyses confirmed the removal of cellular components, preserving collagen and reducing glycosaminoglycans. The scaffolds were nontoxic. While the ultimate tensile strength remained unchanged, the compressive modulus decreased significantly after decellularization. The camel meniscus showed compressive properties comparable to those of the intact human meniscus. Decellularized menisci in all three species had greater porosity and collagen fiber alignment, and the collagen content of decellularized camel meniscus was comparable to that of native human meniscus. In a subcutaneous xenogeneic rat model, decellularized camel meniscus scaffolds exhibited a favorable host response compared to human and sheep scaffolds, characterized by reduced inflammatory infiltration, robust fibroblast migration into the scaffold interior, and slower degradation after 4 weeks. Decellularized camel meniscus represents a preclinical xenogeneic scaffold candidate for meniscus regeneration, particularly in regions where porcine tissues are inaccessible and human allografts are scarce. Its favorable preclinical remodeling profile and dimensional compatibility with human tissue support further validation in large‐animal intra‐articular models prior to clinical translation.