RESUMEN
Bone tissue engineering using stem cells to build bone directly on a scaffold matrix often fails due to lack of oxygen at the injury site. This may be avoided by following the endochondral ossification route; herein, a cartilage template is promoted first, which can survive hypoxic environments, followed by its hypertrophy and ossification. However, hypertrophy is so far only achieved using biological factors. This work introduces a Bioglass-Poly(lactic-co-glycolic acid@fibrin (Bg-PLGA@fibrin) construct where a fibrin hydrogel infiltrates and encapsulates a porous Bg-PLGA. The hypothesis is that mesenchymal stem cells (MSCs) loaded in the fibrin gel and induced into chondrogenesis degrade the gel and become hypertrophic upon reaching the stiffer, bioactive Bg-PLGA core, without external induction factors. Results show that Bg-PLGA@fibrin induces hypertrophy, as well as matrix mineralization and osteogenesis; it also promotes a change in morphology of the MSCs at the gel/scaffold interface, possibly a sign of osteoblast-like differentiation of hypertrophic chondrocytes. Thus, the Bg-PLGA@fibrin construct can sequentially support the different phases of endochondral ossification purely based on material cues. This may facilitate clinical translation by decreasing in-vitro cell culture time pre-implantation and the complexity associated with the use of external induction factors.
Asunto(s)
Osteogénesis , Andamios del Tejido , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Glicoles , Fibrina , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos , Hipertrofia , CondrogénesisRESUMEN
Perfluorocarbon (PFC) emulsions are capable of absorbing large quantities of oxygen. They are widely used as blood alternates for quick oxygenation of tissues. However, they are unsuitable for applications where sustained oxygen supply is desired over an extended period of time. Here, we have designed a new PFC oxygen delivery system that combines perfluorodecalin with graphene oxide (GO), where GO acts both as an emulsifier and a stabilizing agent. The resulting emulsions (PFC@GO) release oxygen at least one order of magnitude slower than emulsions prepared with other common surfactants. The release rate can be controlled by varying the thickness of the GO layer. Controlled release of oxygen make these emulsions excellent oxygen carriers for applications where sustained oxygen delivery is required e.g. in tissue regeneration and vascular wound healing.