Decellularization‐Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair

Abstract

Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, we propose a novel strategy of post‐decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix. To implement this strategy, a human‐derived rosiglitazone‐loaded decellularized extracellular matrix (R‐dECM) is developed. R‐dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R‐dECM protects the migration and collagen synthesis abilities of tendon‐derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R‐dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R‐dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of our proposed strategy. And R‐dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provide a novel bioactive scaffold with the potential to enhance the long‐term clinical outcomes of xenogeneic tendon grafts.This article is protected by copyright. All rights reserved

Design approaches for 3D cell culture and 3D bioprinting platforms

“…38,39 Cells seeded directly in dECM scaffolds has been used as tissue implants for regenerative medicine, due to their low immunogenicity and higher host tolerance. [40][41][42][43] The source of the dECM scaffolds dictates the fate of the tissue. For example, hydroxyapatite rich bone-derived dECM induces osteogenic differentiation in stem cells; 44,45 brain-derived dECM is rich in collagen I, collagen IV, FIG.…”