TGF‐β3 immobilized PLGA‐gelatin/chondroitin sulfate/hyaluronic acid hybrid scaffold for cartilage regeneration

Abstract

Although most in vitro studies indicate that transforming growth factor β3 (TGF-β3) immobilized scaffold is suitable for cartilage tissue engineering, in vivo studies of implanting immobilized scaffold for chondral defect repair are still lacking. This study is to evaluate the potentials of TGF-β3 immobilized poly-(lactic-co-glycolic acid)-gelatin/chondroitin sulfate/hyaluronic acid (PLGA-GCH) hybrid scaffold for cartilage regeneration. The scaffold was fabricated by incorporating GCH micro-sponges into PLGA frameworks and then crosslinked with TGF-β3 to mimic natural cartilaginous extra cellular matrix (ECM). In vitro study demonstrated that MSCs proliferated vigorously and produced abundant ECM on scaffold. The immunohistochemistry staining and alcian blue staining confirmed the cartilaginous ECM production. The chondrogenic differentiation of MSCs on scaffold was proved by the expression of collagen II gene in mRNA and protein level. Then MSCs/TGF-β3 immobilized scaffolds were implanted in rabbits for chondral defects repair. After eight weeks, histological observation showed that differentiated MSCs were located in lacunae within the metachromatic staining matrix and exhibited typical chondrocyte morphology. Histological grading scores also indicated the congruent cartilage was regenerated. In conclusion, the TGF-β3 immobilized PLGA-GCH hybrid scaffold has great potential in constructing the tissue-engineered cartilage.

Enhancing cell migration in shape-memory alginate–collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair

“…(63) This strategy may prolong the retention of the active cues in the scaffold environment, and has been successfully applied for many biomedical applications including bone (64) and cartilage. (65) However, short-term TGF-ß3 exposure in loaded scaffolds did positively influence subsequent collagen deposition by MSCs. This is consistent with the work by Huang et al…”

Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

“…92 The versatility and biocompatibility of HA has attracted attention for the delivery of growth factors and other biological molecules in tissue engineering scaffolds. 18 Recent approaches have included the delivery of signaling molecules, such as simvastatin, 80 vascular endothelial growth factor, 79,84 platelet-derived growth factor, 84 transforming growth factor beta-1 (TGF-b1), 77 TGF-b3, 76 bone morphogenetic protein-2 (BMP-2), 79 phosphatidylserine, 78 and fibronectin. 85 Bae et al 80 fabricated HA hydrogels loaded with simvastatin prior to photocrosslinking to entrap the molecule within the entangled gel matrix.…”

“…56 A combination of HA, CS, and gelatin was fabricated into tri-co-polymer sponges and incorporated into a poly(lactic-co-glycolic acid) (PLGA) framework. 76 Additionally, the scaffolds were loaded with immobilized TGF-b3 and implanted in fullthickness cartilage defects in New Zealand white rabbits (Table 4). 76 Wang et al 50 employed a strategy of using solely raw materials to mimic the ECM of the dermis for skin tissue engineering grafts.…”

“…76 Additionally, the scaffolds were loaded with immobilized TGF-b3 and implanted in fullthickness cartilage defects in New Zealand white rabbits (Table 4). 76 Wang et al 50 employed a strategy of using solely raw materials to mimic the ECM of the dermis for skin tissue engineering grafts. The scaffold matrix consisted of collagen, CS, and HA with different ratios of each component, and was tested for optimal construct properties ( Table 5).…”

The Potential of Human Embryonic Stem Cells for Articular Cartilage Repair and Osteoarthritis Treatment

“…One approach is to incorporate pro-chondrogenic factors into biomaterials. Biomaterial scaffolds impregnated with BMP, TGF-β, or IGF maintain the differentiated phenotype of adult chondrocytes and promote chondrogenesis by MSC in vitro [166][167][168][169], and successful in vivo repair of articular cartilage defects in animal models has been reported in some studies using MSC seeded into TGF-β-containing biomaterial scaffolds [169,170]. However, other studies using a similar approach did not result in improved in vivo cartilage repair [171,172], and in one case led to a foreign body reaction [171].…”