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.
Scaffold porosity plays an important role in bone tissue engineering as macropores promote cell migration and micropores promote protein adsorption and cell adhesion. Currently, most methods use complex, multi-step processes to create dual-scale porosity in composite scaffolds, and no studies evaluate the effect of microporosity on the bioactivity of composite scaffolds with dual porosity. To fill this gap, a simple solvent casting and porogen leaching technique using paraffin microspheres as a porogen and CitriSolv as the leaching solvent to prepare macroporous Bioglass-poly(lactic-co-glycolic acid) (Bg-PLGA) scaffolds with intrinsic micropores (1-10 μm) in the PLGA matrix is proposed, and the effect of microporosity on the bioactivity of the scaffolds is analyzed. PLGA matrix microporosity induces larger apatite deposition upon immersion in simulated body fluid, as well as enhanced protein adsorption upon contact with serum, compared to non-microporous scaffolds. Also, mesenchymal cells cultured on the microporous scaffolds show extensive matrix deposition. These results highlight this method as a simple and effective technique to produce dual-porosity scaffolds that are excellent candidates for bone tissue engineering, as their enhanced bioactivity, protein adsorption, and the extensive matrix deposition observed in-vitro are good indicators of fast bone integration upon implantation.
Porosity affects performance of scaffolds for bone tissue engineering both in vitro and in vivo. Macropores (i.e., pores with a diameter >100 μm) are essential for cellular infiltration; micropores (i.e., pores with a diameter of 1–10 μm) promote cell adhesion and facilitate nutrient absorption. Scaffolds containing both macropores and micropores exploit the advantages of both pore sizes and have excellent osteogenic properties. Nanopores (i.e., pores with a diameter of 1–50 nm) can be included as well, to improve cell–material interactions by further enhancing the surface area of the scaffold. This article reviews fabrication techniques and properties of scaffolds with multiscale porosity, focusing on glass, ceramic, polymeric, and composite scaffolds. After discussing the structure of bone and how it inspired scaffolds for bone tissue engineering, pore nomenclature is introduced. Then, the techniques used to induce multiscale porosity, the nature of the pores created, and the effects of scaffold porosity on mechanical properties and biological activity of the scaffolds are discussed. The review concludes by providing an outlook for this field, including advancements that are made possible by computational modeling and artificial intelligence.
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.
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