Silk fibroin/methacrylated gelatine/hydroxyapatite biomimetic nanofibrous membranes for guided bone regeneration.

By mimicking in vivo bionic microenvironment and promoting osteogenic differentiation, the hybrid organic-inorganic nanofibrous membranes provide promising potential for guided bone regeneration (GBR) in the treatment of clinical bone defects. To develop a degradable and osteogenic membrane for GBR by combining the natural biomacromolecule silk fibroin (SF) and gelatine with the bioactive nano hydroxyapatite (nHA), the anhydride-modified gelatine-nano hydroxyapatite (GelMA-nHA) composites were synthesized in situ and introduced into silk fibroin to prepare nanofibrous membranes with different ratios using electrospinning and photocrosslinking. The nanofibrous membranes, particularly those with a mass ratio of 7:2:1, were found to exhibit satisfactory elongation at break up to 110 %, maintain the nanofibrous structure for up to 28 days, and rapidly form bone-like apatite within 3 days, thus offering advantages when it comes to guided bone regeneration. In vitro cell results showed that the SF/GelMA/nHA membranes had excellent biocompatibility and enhanced osteogenic differentiation of hBMSCs. In vivo studies revealed that the hybrid composite membranes can improve bone regeneration of critical-sized calvarial defects in rat model. Therefore, the novel hybrid nanofibrous membrane is proposed to be a alternative candidate for creating a bionic microenvironment that promotes bone regeneration, indicating their potential application to bone injury treatment.

Biomimetic Membranes of Methacrylated Gelatin/Nanohydroxyapatite/Poly(l-Lactic Acid) for Enhanced Bone Regeneration.

Nanofibrous poly(l-lactic acid) (PLLA) membrane-simulated extracellular matrices (ECMs) can be used in the biomedical field. However, the hydrophobic nature and poor osteoinductive property of PLLA limit its application in guided bone regeneration (GBR). In this work, a methacrylated gelatin/nano-HA (GelMA/nHA) complex was first synthesized in situ and then introduced into PLLA to fabricate biomimetic GelMA/nHA/PLLA membranes, mimicking the nanofibrous architecture and composition of ECMs by electrospinning and photocrosslinking. Compared to PLLA and GelMA/PLLA membranes, the novel GelMA/nHA/PLLA membranes demonstrated better tensile, hydrophilic, water sorption, and degradation properties. An in vitro biological evaluation indicated that the membranes promoted human bone marrow-derived mesenchymal stem cell (hBMSC) proliferation, adhesion, and osteogenic differentiation. Critical-sized defects in rat models were used to evaluate the bone regeneration performances of the three kinds of membranes in vivo, and the GelMA/nHA/PLLA membranes demonstrated excellent osteogenic regeneration potential. Therefore, GelMA/nHA/PLLA membranes have wide application prospects in bioengineering applications such as GBR treatment.

Fabrication of protease XIV-loaded microspheres for cell spreading in silk fibroin hydrogels.

Due to their excellent mechanical strength and biocompatibility, silk fibroin(SF) hydrogels can serve as ideal scaffolds. However, their slow rate of natural degradation limits the space available for cell proliferation, which hinders their application. In this study, litchi-like calcium carbonate@hydroxyapatite (CaCO3@HA) porous microspheres loaded with proteases from Streptomyces griseus (XIV) were used as drug carriers to regulate the biodegradation rate of SF hydrogels. The results showed that litchi-like CaCO3@HA microspheres with different phase compositions could be prepared by changing the hydrothermal reaction time. The CaCO3@HA microspheres controlled the release of Ca ions, which was beneficial for the osteogenic differentiation of mesenchymal stem cells (MSCs). The adsorption and release of protease XIV from the CaCO3@HA microcarriers indicated that the loading and release amount can be controlled with the initial drug concentration. The weight loss test and SEM observation showed that the degradation of the fibroin hydrogel could be controlled by altering the amount of protease XIV-loaded CaCO3@HA microspheres. A three-dimensional (3D) cell encapsulation experiment proved that incorporation of the SF hydrogel with protease XIV-loaded microspheres promoted cell dispersal and spreading, suggesting that the controlled release of protease XIV can regulate hydrogel degradation. SF hydrogels incorporated with protease XIV-loaded microspheres are suitable for cell growth and proliferation and are expected to serve as excellent bone tissue engineering scaffolds.