Fabrication of poly(lactide‐co‐glycolide) scaffold filled with fibrin gel, mesenchymal stem cells, and poly(ethylene oxide)‐b‐poly(L‐lysine)/TGF‐β1 plasmid DNA complexes for cartilage restoration in vivo

Abstract

A poly (lactide-co-glycolide) (PLGA) scaffold filled with fibrin gel, mesenchymal stem cells (MSCs) and poly(ethylene oxide)-b-poly (L-lysine) (PEO-b-PLL)/pDNA-TGF-β1 complexes was fabricated and applied in vivo for synchronized regeneration of cartilage and subchondral bone. The PEO-b-PLL/pDNA-TGF-β1 complexes could transfect MSCs in vitro to produce TGF-β1 in situ and up regulate the expression of chondrogenesis-related genes in the construct. The expression of heterogeneous TGF-β1 in vivo declined along with the prolongation of implantation time, and lasted for 3 and 6 weeks in the mRNA and protein levels, respectively. The constructs (Experimental group) of PLGA/fibrin gel/MSCs/(PEO-b-PLL/pDNA-TGF-β1 complexes) were implanted into the osteochondral defects of rabbits to restore the functional cartilages, with gene-absent constructs as the Control. After 12 weeks, the Experimental group regenerated the neo-cartilage and subchondral bone with abundant deposition of glycosaminoglycans (GAGs) and type II collagen. The regenerated tissues had good integration with the host tissues too. By contrast, the defects were only partially repaired by the Control constructs. qRT-PCR results demonstrated that expression of the chondrogenesis-marker genes in the Experimental group was significantly higher than that of the Control group, and was very close to that of the normal cartilage tissue.

Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery

“…coagulation cascade, and is currently used in a clinical setting as biological glue for surgical procedures or as a scaffold for therapeutic strategies [23,24]. Alginate is a natural polymer (polysaccharide) extracted from brown algae, and clinical-grade alginates are available for use in human therapeutics [25].…”

Alterations of the subchondral bone in osteochondral repair – translational data and clinical evidence

“…This theory is supported by the presence of type I and type X collagen in the cartilaginous repair tissue (Kaul et al, 2012). Many factors, among which parathyroid hormone (PTH [1-34]) (Orth et al, 2013a), Sox9 (Cucchiarini et al., 2013, enamel matrix derivative (Kiss et al, 2012), bone morphogenetic proteins and their inhibitors (Rosen, 2006;Ruschke et al, 2012), IGF-I (Kim et al, 2013;Madry et al, 2005), or TGF-β (Li et al, 2013; Re'em et al., 2012;Serra et al, 1997), have either been shown or suggested to affect structural patterns of subchondral bone repair in animal models of osteochondral defects in vivo. An imbalance between them may impair the regulation of osteochondral repair.…”

Stem Cell Therapy for Cartilage Defects

“…Natural scaffolds include substances such as carbohydrate-based materials such as chitosan (Ye et al 2014;García Cruz et al 2012;Alves da Silva et al 2011), hyaluronate (Son et al 2013;Toh et al 2012) or even protein-based structures such as collagen (Zhang et al 2012(Zhang et al , 2013aMurphy et al 2012), fibrin (Diederichs et al 2012;Park et al 2011), gelatin (Klangjorhor et al 2012;Pruksakorn et al 2009) and chondroitin (Chen et al 2013;Park et al 2010;Varghese et al 2008). Synthetic scaffolds successfully used include polyglycolic acid, polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol and polycaprolactone (Hidalgo et al 2013;Childs et al 2013;Zhang et al 2013b;Li et al 2013).…”