Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

Preparation and application of chitosan-based medical electrospun nanofibers.

Chitosan is a kind of polysaccharide cationic polymer, which has excellent biocompatibility, biodegradability and biological activity. In recent years, chitosan has been widely used as medical materials because of its non-toxicity, non-immunogenicity and rich sources. This paper reviews chitosan chemistry, the basic principles and influence of electrospinning technology, the blending of chitosan with polyethylene oxide, polyvinyl alcohol, polycaprolactone, polylactic acid, protein, polysaccharide and other polymer materials, the blending of chitosan with oxides, metals, carbon-based and other inorganic substances for electrospinning, the application of chitosan electrospinning nanofibers in medical field and its mechanism in clinical application. In order to provide reference for the in-depth study of electrospinning technology in the field of medical and health.

Wirelessly Powered Electrical-Stimulation Based on Biodegradable 3D Piezoelectric Scaffolds Promotes the Spinal Cord Injury Repair.

An electroactive scaffold integrated with noninvasive in vivo electrical-stimulation (ES) capability shows great promise in the repair and regeneration of damaged tissues. Developing high-performance piezoelectric biomaterials which can simultaneously serve as both a biodegradable tissue scaffold and controllable electrical stimulator remains a great challenge. Herein, we constructed a biodegradable high-performance 3D piezoelectric scaffold with ultrasound (US)-driven wireless ES capability, and demonstrated its successful application for the repair of spinal cord injuries in a rat model. The 3D multichannel piezoelectric scaffold was prepared by electrospinning of poly(lactic acid) (PLA) nanofibers incorporated with biodegradable high-performance piezoelectric potassium sodium niobate (K0.5Na0.5NbO3, KNN) nanowires. With programmed US irradiation as a remote mechanical stimulus, the on-demand in vivo ES with an adjustable timeline, duration, and strength can be delivered by the 3D piezoelectric scaffold. Under proper US excitation, the 3D tissue scaffolds made of the piezoelectric composite nanofibers can accelerate the recovery of motor functions and enhance the repair of spinal cord injury. The immunohistofluorescence investigation indicated that the 3D piezoelectric scaffolds combined with the US-driven in vivo ES promoted neural stem cell differentiation and endogenous angiogenesis in the lesion. This work highlights the potential application of a biodegradable high-performance piezoelectric scaffold providing US-driven on-demand electrical cues for regenerative medicine.

Injectable shape memory hydroxyethyl cellulose/soy protein isolate based composite sponge with antibacterial property for rapid noncompressible hemorrhage and prevention of wound infection.

Uncontrollable hemorrhage and subsequent wound infection are severe threats to life, especially for the deep noncompressible massive bleeding. However, traditional hemostatic materials are ineffective for extreme bleeding and subsequent wound infection. Here, we prepared an injectable shape memory hydroxyethyl cellulose/soy protein isolate based composite sponge (EHSS) for rapid noncompressible hemorrhage and prevention of wound infection. The nano silver (AgNPs)-loaded shape memory sponge (EHP@Ag) was fabricated by mussel-inspired polydopamine coating EHSS sponge, then reducing and immobilizing AgNPs in situ. The EHP@Ag sponges showed rapid blood-triggered shape recovery speed, which is beneficial for administering noncompressible hemorrhage. The results of the hemostatic experiment in vivo demonstrated that EHP@Ag sponge exhibited a desirable hemostasis effect (hemostasis time: 22.75 ± 3.86 s, blood loss: 285.25 ± 24.93 mg) compared to the commercial gelatin sponge (hemostasis time: 49.25 ± 3.30 s, blood loss: 755.50 ± 24.45 mg). Meanwhile, the EHP@Ag sponge has an efficient antibacterial property. Furthermore, the antibacterial experiment in vivo showed that the EHP@Ag sponges could kill bacteria effectively and reduce the bacteria-induced inflammatory response. In summary, the shape memory sponges can quickly control bleeding and avoid bacterial infection, which shows great potential for clinical application as a multifunctional hemostatic agent.

Natural Flammulina velutipes-Based Nerve Guidance Conduit as a Potential Biomaterial for Peripheral Nerve Regeneration: In Vitro and In Vivo Studies.

The treatment and repair of serious peripheral nerve injuries remain challenging in the clinical practice, while the application of multifunctional nerve guidance conduits (NGCs) based on naturally derived polymers has attracted much attention in recent years because of their excellent physicochemical properties and biological characteristics. Flammulina velutipes (Curt. ex FV) is a popular edible mushroom characterized by hollow tubular structures, antibacterial activities, and high nutritional properties. In this study, FV is utilized to construct NGCs (labeled FVC) via a freeze-drying technique without chemical modifications. The morphology, physical properties, cellular biocompatibility, antibacterial properties, and nerve regeneration capacity of FVC were assessed both in vitro and in vivo. FVC is composed of hollow tubes and evenly irregular interconnected micropores with 73.8 ± 5.5% porosity and 476.1 ± 12.9 µm hollow tube diameter. The inner surface of the FVC presents multiple microgrooves elongated parallel to the long axis. Moreover, FVC possessed strong antibacterial activity and could inhibit Gram-positive Staphylococcus aureus growth by up to 96.0% and Gram-negative Escherichia coli growth by up to 94.8% in vitro. FVC exhibited excellent biocompatibility and effectively promoted PC-12 cell proliferation and elongation in vitro. When applied to repair critical-sized sciatic nerve defects, FVC could effectively stimulate nerve functional recovery and axonal outgrowth in a rat model. Interestingly, Western blot analysis indicated that growth-associated protein 43 (GAP-43) had increased expression levels in the FVC group compared with the autograft group. This result suggested that by activating the Janus activated kinase2 (JAK2)/Phosphorylation ofsignal transducer and activator of transcription-3 (STAT3) signaling pathway, FVC upregulated Phosphorylation of signal transducer and activator of transcription-3 (P-STAT3) in vivo, resulting in the secretion of GAP-43. Collectively, a natural NGC FVC was fabricated based on FV without chemical modifications. The morphology, physical properties, cellular biocompatibility, antibacterial properties, and nerve regeneration capacity of FVC provide new insights for its further optimization and application in the field of nerve tissue engineering.

Green fabrication of seedbed-like Flammulina velutipes polysaccharides-derived scaffolds accelerating full-thickness skin wound healing accompanied by hair follicle regeneration.

A novel seedbed-like scaffold was firstly fabricated by the "frozen sectioning" processing method using Flammulina velutipes as a raw material. The Flammulina velutipes polysaccharides scaffold is composed of a natural structure imitating the "ground" (connected and aligned hollow tubes with porous walls). Meanwhile, its biologically active components include polysaccharides and proteins, mimicking the "plant nutrition" in the seedbed. To further optimize the ground and nutrition components, Flammulina velutipes polysaccharides-derived scaffolds (FPDSs) were fabricated via the treatment of original Flammulina velutipes polysaccharides scaffold (labeled FPS) by NaOH, cysteine (labeled as FPS/NaOH, FPS/Cys, respectively). FPDSs were characterized by SEM, FTIR, XRD, water absorption and retention, and mechanical evaluations. From the results, FPS/NaOH and FPS/Cys lost the characteristic big tubes of original strips and had higher water absorption capacities comparing to FPS. Simultaneously, FPS/NaOH had better ductility, FPS/Cys had showed increased stiffness. Biological activities of FPDSs were tested against different types of bacteria exhibiting excellent anti-bacterial activity, and FPS/NaOH and FPS/Cys had dramatically higher anti-bacterial activity than FPS. The cytocompatibility of FPDSs was evaluated utilizing mouse fibroblast cell line (L929), and all FPDSs showed good cytocompatibility. The FPDSs were further applied to a rat full-thickness skin wound model, and they all exhibited obviously accelerated re-epithelialization, among which FPS/NaOH showed the greatest efficiency. FPS/NaOH could shorten the wound-healing process as evidenced by dynamic alterations of the expression levels of specific stagewise markers in the healing areas. Similarly, FPS/NaOH can efficiently induce hair follicle regeneration in the healing skin tissues. In summary, FPDSs exhibit potential functions as seedbeds to promote the regeneration of the "seed" including hair follicles and injured skin, opening a new avenue for wound healing.

Aligned soy protein isolate-modified poly(L-lactic acid) nanofibrous conduits enhanced peripheral nerve regeneration.

OBJECTIVE: Repair and regeneration of peripheral nerve defect by engineered conduits have greatly advanced in the past decades while still facing great challenges. APPROACH: In this work, we fabricated a new highly oriented poly(L-lactic acid) (PLLA)/soy protein isolate (SPI) nanofibrous conduit (HO-PSNC) for nerve regeneration. MAIN RESULTS: Firstly, we observed that SPI could efficiently modify PLLA for the electrospinning of PLLA/SPI nanofibers with enhanced physical and biological properties. Incorporation of SPI decreased the fiber diameter and ductility of PLLA/SPI nanofibrous films (PSNFs), improved the tensile strength and surface wettability of PSNFs and increased the in vivo degradability of the PSNFs. When the hybrid ratio of SPI was 20 and 40%, PSNFs could efficiently promote neural cell extension and differentiation in vitro. Based on these data, 20% SPI (PSNF-20) was chosen for further investigation. Next, PSNF-20 with different fiber orientations (random/low orientation, medium, and high orientation, respectively) were developed and used for evaluating neural cell behaviors on the materials. Results revealed that the PSNF-20 with highly oriented nanofibers (HO-PSNF-20) or mediumly oriented nanofibers (MO-PSNF-20) showed a better performance in directing cell extension and enhancing neurite outgrowth. Finally, the highly oriented nanofibers conduits (HO-PSNC-20) were used to bridge sciatic nerve defect in rats with highly oriented PLLA and autografts as controls. HO-PSNC-20 exhibited a significant promotion in nerve regeneration and functional reconstruction comparing to highly oriented PLLA as proven by the evaluations of walking track, electrophysiology, toluidine blue nerve staining, transmission electron microscopy, neural factors staining and qPCR, and gastrocnemius histology. SIGNIFICANCE: In conclusion, nerve conduit fabricated from aligned electrospinning of SPI-modified PLLA nanofibers is promising for peripheral nerve regeneration.

Accelerated skin wound healing by soy protein isolate-modified hydroxypropyl chitosan composite films.

In this study, a series of hydroxypropyl chitosan (HPCS)/soy protein isolate (SPI) composite films (HCSFs) with different SPI contents were developed via crosslinking, solution casting, and evaporation process. Effects of the SPI content on the structure and physical properties of the HCSFs were characterized by Fourier transform infrared spectroscopy, X-ray diffraction patterns, scanning electron microscopy, swelling kinetics analysis, and mechanical testing. The HCSFs exhibited a lower swelling ratio with an increase in the SPI content. The tensile strength was in a tunable range from 7.88 ±â€¯3.08 to 40.44 ±â€¯2.31 MPa by adjusting the SPI content. Cytocompatibility and hemocompatibility of the HCSFs were evaluated by a series of in vitro assays, including MTT assay, live/dead assay, cell morphology observation, hemolysis ratio testing, and plasma recalcification time measurement. Results showed that the HCSFs support L929 cells attachment and proliferation without obvious hemolysis, indicating good cytocompatibility and hemocompatibility. The potential of resultant HCSFs as the wound dressings was investigated using a full-thickness skin wound model in rats. Results exhibited that the HCSFs with 50% SPI content had the fastest healing speed and the best skin regeneration efficiency and may be a potential candidate as the wound dressing.