Biofunctionalized Structure and Ingredient Mimicking Scaffolds Achieving Recruitment and Chondrogenesis for Staged Cartilage Regeneration

Abstract

It remains scientifically challenging to regenerate injured cartilage in orthopedics. Recently, an endogenous cell recruitment strategy based on a combination of acellular scaffolds and chemoattractants to specifically and effectively recruit host cells and promote chondrogenic differentiation has brought new hope for in situ articular cartilage regeneration. In this study, a transforming growth factor-β3 (TGF-β3)-loaded biomimetic natural scaffold based on demineralized cancellous bone (DCB) and acellular cartilage extracellular matrix (ECM) was developed and found to improve chondral repair by enhancing cell migration and chondrogenesis. The DCB/ECM scaffold has porous microstructures (pore size: 67.76 ± 8.95 μm; porosity: 71.04 ± 1.62%), allowing the prolonged release of TGF-β3 (up to 50% after 42 days in vitro) and infrapatellar fat pad adipose-derived stem cells (IPFSCs) that maintain high cell viability (>96%) and favorable cell distribution and phenotype after seeding onto the DCB/ECM scaffold. The DCB/ECM scaffold itself can also provide a sustained release system to effectively promote IPFSC migration (nearly twofold in vitro). Moreover, TGF-β3 loaded on scaffolds showed enhanced chondrogenic differentiation (such as collagen II, ACAN, and SOX9) of IPFSCs after 3 weeks of culture. After implanting the composite scaffold into the knee joints of rabbits, enhanced chondrogenic differentiation was discovered at 1, 2, and 4 weeks post-surgery, and improved repair of cartilage defects in terms of biochemical, biomechanical, radiological, and histological results was identified at 3 and 6 months post-implantation. To conclude, our study demonstrates that the growth factor (GF)-loaded scaffold can facilitate cell homing, migration, and chondrogenic differentiation and promote the reconstructive effects of in vivo cartilage formation, revealing that this staged regeneration strategy combined with endogenous cell recruitment and pro-chondrogenesis is promising for in situ articular cartilage regeneration.

Hierarchical porous ECM scaffolds incorporating GDF-5 fabricated by cryogenic 3D printing to promote articular cartilage regeneration

“…Among many biomaterials, decellularized cartilage extracellular matrix (ECM) has been widely used because of its outstanding biocompatibility and biochemical cue retention [ 8 , 9 ]. Previous studies by our group have also demonstrated the positive effect of ECM on cartilage regeneration [ 10 , 11 ]. However, traditional ECM scaffolds are usually lyophilized.…”

“…Decellularized cartilage ECM was prepared by a combination of chemical and physical methods based on previous studies with slight modifications [ 10 , 11 , 25 ]. The specific experimental procedure is detailed in Supplementary File section 1 .1.…”

Integrated bioactive scaffold with aptamer‐targeted stem cell recruitment and growth factor‐induced pro‐differentiation effects for anisotropic meniscal regeneration

“…It has been well established that sufficient ESPCs are crucial for the meniscal healing process; however, the inherent recruitment and mobilization of ESPCs to the injured sites are inadequate for the repair of meniscal injury. 29 , 30 , 39 Although some chemokines and GFs, such as stromal cell‐derived factor‐1 and platelet‐derived GF‐BB, have been used to promote ESPC migration toward meniscal injury sites, the nonspecific mobilization induced by these factors, including the migration of proinflammatory or endothelial cells, might excessively activate inflammatory responses and thus impede meniscal regeneration. 40 , 41 Therefore, it is important to discover a chemoattractant that can specifically recognize and efficiently recruit ESPCs for endogenous meniscal regeneration.…”

Mg-BGNs/DCECM Composite Scaffold for Cartilage Regeneration: A Preliminary In Vitro Study

“…In our previous studies, we also found that cartilage-derived extracellular matrix scaffolds can promote stem cell migration, proliferation, cartilage differentiation, and enhance in vivo cartilage defect repair; therefore, it can be considered a promising alternative tissue engineering scaffold for the treatment of articular cartilage defects [12,13]. However, this cartilage-derived matrix, though a promising biomaterial for cartilage regeneration, still has some challenges.…”