Novel Bioinspired Nerve Scaffold with High Synchrony between Biodegradation and Nerve Regeneration for Repair of Peripheral Nerve Injury.

The morphological structure reconstruction and functional recovery of long-distance peripheral nerve injury (PNI) are global medical challenges. Biodegradable nerve scaffolds that provide mechanical support for the growth and extension of neurites are a desired way to repair long-distance PNI. However, the synchrony of scaffold degradation and nerve regeneration is still challenging. Here, a novel bioinspired multichannel nerve guide conduit (MNGC) with topographical cues based on silk fibroin and ε-polylysine modification was constructed. This conduit (SF(A) + PLL MNGC) exhibited sufficient mechanical strength, excellent degradability, and favorable promotion of cell growth. Peripheral nerve repairing was evaluated by an in vivo 10 mm rat sciatic model. In vivo evidence demonstrated that SF(A) + PLL MNGC was completely biodegraded in the body within 4 weeks after providing sufficient physical support and guide for neurite extension, and a 10 mm sciatic nerve defect was effectively repaired without scar formation, indicating a high synchronous effect of scaffold biodegradation and nerve regeneration. More importantly, the regenerated nerve of the SF(A) + PLL MNGC group showed comparable morphological reconstruction and functional recovery to that of autologous nerve transplantation. This work proved that the designed SF(A) + PLL MNGC has potential for application in long-distance PNI repair in the clinic.

Electrospun Piezoelectric Scaffold with External Mechanical Stimulation for Promoting Regeneration of Peripheral Nerve Injury.

Safe and efficient provision of electrical stimulation (ES) for nerve repair and regeneration is a problem that needs to be addressed. In this study, a silk fibroin/poly(vinylidene fluoride-co-hexafluoropropylene)/Ti3C2Tx (SF/PVDF-HFP/MXene) composite scaffold with piezoelectricity was developed by electrospinning technology. MXene was loaded to the scaffold to enhance the piezoelectric properties (Output voltage reaches up to 100 mV), mechanical properties, and antibacterial activity. Cell experiments demonstrated piezoelectric stimulation under external ultrasonication for promoting the growth and proliferation of Schwann cells (SCs) cultured on this electrospun scaffold. Further in vivo study with rat sciatic nerve injury model revealed that the SF/PVDF-HFP/MXene nerve conduit could induce the proliferation of SCs, enhance the elongation of axon, and promote axonal myelination. Under the piezoelectric effect of this nerve scaffold, the rats with regenerative nerve exhibited a favorable recovery effect of motor and sensory function, indicating a safe and feasible method of using this SF/PVDF-HFP/MXene piezoelectric scaffold for ES provision in vivo.

Hybrid membrane of flat silk cocoon and carboxymethyl chitosan formed through hot pressing promotes wound healing and repair in a rat model.

Clinical wound management is always a relatively urgent problem. Moreover, wounds, especially severe wounds with excessive tension or excessive movement are prone to tissue infection, necrosis, and other negative effects during healing. Therefore, research has aimed to develop low-cost complementary treatments to address the urgent need for an innovative low-cost dressing that can adapt to high mechanical requirements and complex wound conditions. At present, tissue engineering to produce artificial skin with a structure similar to that of normal skin is one effective method to solve this challenge in the regeneration and repair of serious wounds. The present study hot pressed flat silk cocoons (FSC) with carboxymethyl chitosan (CMCS) to generate a cross-linked binding without enzymes or cross-linking agents that simulated the 3D structural composites of the skin cuticle. This hybrid membrane showed potential to reduce inflammatory cells and promote neovascularization in skin wound repair. After hot pressing at 130°C and 20 Mpa, the FSC/CMCS composite material was denser than FSC, showed strong light transmission, and could be arbitrarily cut. Simulating the normal skin tissue structure, the hybrid membrane overcame the poor mechanical properties of traditional support materials. Moreover, the combination of protein and polysaccharide simulated the extracellular matrix, thus providing better biocompatibility. The results of this study also demonstrated the excellent mechanical properties of the FSC/CMCS composite support material, which also provided a low-cost and environmentally friendly process for making dressings. In addition, the results of this study preliminarily reveal the mechanism by which the scaffolds promoted the healing of full-thickness skin defects on the back of SD rats. In vivo experiments using a full-thickness skin defect model showed that the FSC/CMCS membranes significantly promoted the rate of wound healing and also showed good effects on blood vessel formation and reduced inflammatory reactions. This bionic support structure, with excellent repair efficacy on deep skin defect wounds, showed potential to further improve the available biomaterial systems, such as skin and other soft tissues.

Multifunctional Dual Ionic-Covalent Membranes for Wound Healing.

Wound healing generally has four stages: hemostasis, inflammation, proliferation, and remolding. Most wound dressings only just take one or two phases into account. Herein, to develop a novel wound dressing that works at different stages, the blended alginate sodium/carboxymethyl chitosan membranes with a hydrogel-like structure are fabricated through a freeze-drying process together with a dual-ion (Sr2+ and Zn2+) cross-linking approach. The fabricated membranes show excellent properties in the swelling ratio, water vapor transmission rate, tensile strength, sustained release, cell adhesiveness, and biocompatibility, proving its general performance for application in wound healing. In particular, the membranes with optimal ion concentrations of 45 mM Sr2+ and 0.74 mM Zn2+ presented the antibacterial activity and accelerating function of wound healing. More specifically, the formation of epithelium and blood vessels is evidently advanced compared with a commercial dressing in vivo experiment, and the expression of main growth factors such as epidermal growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor is upregulated which also have good effects on the remolding of skin. The prepared wound dressings in this study have good effects on each stage of wound healing, which is important for the healing of chronic wounds. It provides more choices for wound healing, especially for chronic wound healing.

Topical application of silk fibroin-based hydrogel in preventing hypertrophic scars.

Current medications for the treatment of hypertrophic scars suffer from bottlenecks of limited therapeutic efficacy and a slow recovery rate. Silk fibroin (SF) has gained attention for its ability to promote wound healing in burns and cutaneous wounds, but its therapeutic effects against hypertrophic scar have not been thoroughly investigated. We prepared SF-based hydrogels (SFHs) with various SF concentrations (1.5 %, 3 %, and 6 %) and characterized their physicochemical properties. Cell experiments showed that these SFHs had favorable biocompatibility in vitro. Further animal experiments in rabbits revealed that the SFH (3 %)-treated group achieved scars on their ears that were thinner and significantly lighter in color compared with the negative control group. Moreover, treatment with SFHs reduced the density and led to the orderly arrangement of collagen fibers. It was found that the therapeutic effects of SFHs were attributed to the reduced expression levels of α-smooth muscle actin. These results are the first to demonstrate that SFH can be exploited as an effective therapeutic agent for the treatment of hypertrophic scars.