Composite Superelastic Aerogel Scaffolds Containing Flexible SiO2 Nanofibers Promote Bone Regeneration.

Repairing irregular-shaped bone defects poses enormous challenges. Scaffolds that can fully fit the defect site and simultaneously induce osteogenesis and angiogenesis hold great promise for bone defect healing. This study aimed to produce superelastic organic/inorganic composite aerogel scaffolds by blending silica nanofibers (SiO2 ) and poly (lactic acid)/gelatin (PLA/gel) nanofibers; the content of SiO2 nanofibers is varied from 0-60 wt% (e.g., PLA/gel, PLA/gel/SiO2 -L, PLA/gel/SiO2 -M, and PLA/gel/SiO2 -H for 0%, 20%, 40%, and 60% of SiO2 nanofibers, respectively) to produce a range of scaffolds. The PLA/gel/SiO2 -M scaffold has excellent elasticity and good mechanical properties. In vitro experiments demonstrate that the silicon ions released from PLA/gel/SiO2 -M scaffolds promote the differentiation of rat bone marrow-derived mesenchymal stem cells into osteoblasts, enhancing alkaline phosphatase activity and bone-related genes expressions. The released silicon ions also promote the proliferation of human umbilical vein endothelial cells and the expression of vascular endothelial growth factors, thereby promoting angiogenesis. The assessment of these scaffolds in a calvarial defect model in rats shows good potential of PLA/gel/SiO2 -M to induce bone regeneration as well as promote osteogenesis and angiogenesis. Overall, these organic/inorganic composite scaffolds have good biological activity, which may have broad applications for tissue engineering.

Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration.

Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications. STATEMENT OF SIGNIFICANCE: Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.

Silk fibroin/poly-(L-lactide-co-caprolactone) nanofiber scaffolds loaded with Huangbai Liniment to accelerate diabetic wound healing.

Diabetic infection is a long-term complication difficult to cure. The skin of diabetic patients is prone to damage, the healing is slow after the injury, and the wound occurs repeatedly. Therefore, there is an urgent need to develop an effective method for treating diabetes wounds. In this study, we used the electrospinning technique to load Huangbai Liniment (Compound Phellodendron Liquid, CPL) into Silk fibroin (SF) /poly-(L-lactide-co-caprolactone) (PLCL) to prepare the nanofiber membrane (SP/CPL) to treat the diabetic wound. The morphology and structure of the nanofibers were observed by scanning electron microscope (SEM). The SEM results indicate the smooth and bead free fibers and the diameter of the fiber decreased with increasing drug concentration. The release profile indicates the sustained release of the drug. Moreover, the drug-loaded nanofibers showed inhibitory effects for S.aureus and E.coli. Furthermore, in vitro cell culture studies showed the increased proliferation and adhesion of NIH-3T3 cells on the drug-containing nanofiber membrane. Animal experiments showed that the nanofiber membrane loaded with CPL increases the expression of the TGF-ß signaling pathway and collagen during wound healing, inhibits the expression of pro-inflammatory factors, and thus effectively promotes wound healing in diabetic mice. Therefore, the SP/CPL nanofiber scaffold with CPL loading is a potential candidate for diabetic wound dressings and tissue engineering.

Exploration of the antibacterial and wound healing potential of a PLGA/silk fibroin based electrospun membrane loaded with zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) are known for their antibacterial, antioxidant, and anti-inflammatory activities. Moreover, ZnO NPs can stimulate cell migration, re-epithelialization, and angiogenesis. All these attributes are highly relevant to wound healing. Local administration of ZnO NPs to the wound can be achieved through electrospun nanofibers. We hypothesized that the use of poly(lactide-co-glycolic acid) (PLGA)/silk fibroin (SF) nanofiber-based delivery of ZnO would maintain the bioavailability of NPs on the wound area and synchronization with the unique structural features of electrospun nanofibers, could stimulate wound closure, re-epithelialization, collagen deposition, cellular migration, and angiogenesis. In this study, we fabricated PLGA/SF (PS) nanofibrous (NF) membranes with and without ZnO NPs and extensively characterized them for various physicochemical and biological attributes. Scanning electron microscopy (SEM) revealed smooth fibers and ZnO concentration-dependent increase in the fiber diameter. Transmission electron microscopy (TEM) also confirmed the encapsulation of ZnO NPs in the polymer matrix. The successful loading of ZnO was further confirmed by X-ray diffraction. Furthermore, mechanical testing revealed a ZnO concentration-dependent increase in the tensile strength. Moreover, biocompatibility was evaluated through in vitro cell culture. A mild anti-oxidant activity was also noted mainly due to the presence of silk fibroin. In vitro antibacterial tests revealed a ZnO concentration-dependent increase in antibacterial activity and PLGA/SF/3% ZnO (PSZ3) remained completely active against E. coli and S. aureus. More importantly, NF membranes were evaluated for their in vivo wound healing potential. The PSZ3 NF membrane not only facilitated the early wound closure but also remarkably enhanced the quality of wound healing confirmed through histopathological analysis. Re-epithelialization, granulation tissue formation, collagen deposition, and angiogenesis are some of the key parameters significantly boosted by ZnO loaded composite NF membranes. Based on extensive characterization and biological evaluation, the PSZ3 NF membrane has turned out to be a potential candidate for wound healing applications.