He Wang,Bo Hu,Hong Li,Ge Feng,Shengyuan Pan,Ziqi Chen,Bo Li,Jinlin Song
Purpose Methacrylic anhydride-modified gelatin (GelMA) hydrogels exhibit many beneficial biological features and are widely studied for bone tissue regeneration. However, deficiencies in the mechanical strength, osteogenic factors and mineral ions limit their application in bone defect regeneration. Incorporation of inorganic fillers into GelMA to improve its mechanical properties and bone regenerative ability has been one of the research hotspots. Methods In this work, hydroxyapatite nanofibers (HANFs) were prepared and mineralized in a simulated body fluid to make their components and structure more similar to those of natural bone apatite, and then different amounts of mineralized HANFs (m-HANFs) were incorporated into the GelMA hydrogel to form m-HANFs/GelMA composite hydrogels. The physicochemical properties, biocompatibility and bone regenerative ability of m-HANFs/GelMA were determined in vitro and in vivo. Results The results indicated that m-HANFs with high aspect ratio presented rough and porous surfaces coated with bone-like apatite crystals. The incorporation of biomimetic m-HANFs improved the biocompatibility, mechanical, swelling, degradation and bone regenerative performances of GelMA. However, the improvement in the performance of the composite hydrogel did not continuously increase as the amount of added m-HANFs increased, and the 15m-HANFs/GelMA group exhibited the best swelling and degradation performances and the best bone repair effect in vivo among all the groups. Conclusion The biomimetic m-HANFs/GelMA composite hydrogel can provide a novel option for bone tissue engineering in the future; however, it needs further investigations to optimize the proportions of m-HANFs and GelMA for improving the bone repair effect.
A membrane used for guided bone regeneration (GBR) serves as a bioactive compartment rather than a physical barrier. However, the pure membrane may not provide an optimal microenvironment for bone formation and remodeling. Here, a novel strontium chondroitin sulfate/silk fibroin (SrCS/SF) blend membrane containing microporous structure was fabricated. By increasing incorporation content of SrCS, SrCS/SF membranes exhibit better mechanical properties and higher water retention capacity. In vitro results reveal that higher content of SrCS membranes facilitate osteoblasts proliferation. The evaluation of the osteoimmunomodulatory effects of the membranes reveals that SrCS/SF membranes should have positive effects on modulating the osteoimmune response of macrophages, by downregulating the expression of pro-inflammatory cytokines and the expression of degradation related catabolic genes and upregulating osteogenic factors. It is therefore believed that the developed SrCS/SF membranes should be potentially used as multifunctional bioactive GBR membranes.
Once bone is damaged, a rapid surge of reactive oxygen species (ROS) and anaerobic glycolysis will create an oxidative stress and acidic microenvironment, thus inhibiting osteogenic factor expression and disrupting bone regeneration. To address this, we innovatively developed an alkaline hydrogel-coated poly(ether ether ketone) (PEEK) porous scaffold with VitaFlux functionality in this study. This decorated PEEK scaffold distinct from those hydrogel-perfused scaffolds with obstructed pores still kept its initial 3D-printed pore structure to allow the ingrowth of bone tissues. The results showed that the modified scaffold could not only exhibit significant efficacy in lowering oxidative stress, neutralizing acidic microenvironment, and activating TGF-β1 expression in serum through its inherent alkalinity but also recruit stem cells to the bone defect site and upregulate osteogenic factor expression via the TGF-β1/Smad signaling pathway. This study proved the obvious advantage of the modified scaffold in enhancing bone regeneration by the synergy of immune microenvironment remodeling and osteogenic factor expression enhancement, thus providing a facile method to modify bone scaffold which can facilitate a desirable bone repair process through self-activating the transfer of growth factors between the material and tissues.
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