In vivo restoration of full-thickness cartilage defects by poly(lactide-co-glycolide) sponges filled with fibrin gel, bone marrow mesenchymal stem cells and DNA complexes
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Abstract
A composite construct comprising of bone marrow mesenchymal stem cells (BMSCs), plasmid
DNA encoding transforming growth factor-beta1 (pDNA-TGF-beta1), fibrin gel and poly
(lactide-co-glycolide) (PLGA) sponge was designed and employed to repair articular
cartilage defects. To improve the gene transfection efficiency, a cationized chitosan
derivative N,N,N-trimethyl chitosan chloride (TMC) was employed as the vector. The
TMC/DNA complexes had a transfection efficiency of 9% to BMSCs and showed heterogeneous
TGF-beta1 expression in a 10-day culture period in vitro. In vivo culture of the composite
constructs was performed by implantation into full-thickness cartilage defects of
New Zealand white rabbit joints, using the constructs absence of pDNA-TGF-beta1 or
BMSCs as controls. Heterogeneous expression of TGF-beta1 in vivo was detected at 4
weeks, but its level was decreased in comparison with that of 2 weeks. After implantation
for 12 weeks, the cartilage defects were successfully repaired by the composite constructs
of the experimental group, and the neo-cartilage integrated well with its surrounding
tissue and subchondral bone. Immunohistochemical and glycosaminoglycans (GAGs) staining
confirmed the similar amount and distribution of collagen type II and GAGs in the
regenerated cartilage as that of hyaline cartilage. The cartilage special genes expressed
in the neo-tissue were closer to those of the normal cartilage. An overall score of
2.83 was obtained according to Wakitani's standard. By contrast, only part of the
defects was repaired by the pDNA-TGF-beta1 absence constructs, and no cartilage repair
but fibrous tissue was found for the BMSCs absence constructs. Therefore, combination
of the PLGA sponge/fibrin gel scaffold with BMSCs and gene therapy is an effective
method to restore cartilage defects and may have a great potential for practical applications
in the near future.
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