Bioactive microgel-coated electrospun membrane with cell-instructive interfaces and topology for abdominal wall defect repair.

Current mesh materials used for the clinical treatment of abdominal defects struggle to balance mechanical properties and bioactivity to support tissue remodeling. Therefore, a bioactive microgel-coated electrospinning membrane was designed with the superiority of cell-instructive topology in guiding cell behavior and function for abdominal wall defect reconstruction. The electrostatic spinning technique was employed to prepare a bioabsorbable PLCL fiber membrane with an effective mechanical support. Additionally, decellularized matrix (dECM)-derived bioactive microgels were further coated on the fiber membrane through co-precipitation with dopamine, which was expected to endow cell-instructive hydrophilic interfaces and topological morphologies for cell adhesion. Moreover, the introduction of the dECM into the microgel promoted the myogenic proliferation and differentiation of C2C12 cells. Subsequently, in vivo experiments using a rat abdominal wall defect model demonstrated that the bioactive microgel coating significantly contributed to the reconstruction of intact abdominal wall structures, highlighting its potential for clinical application in promoting the repair of soft tissue defects associated with abdominal wall damage. This study presented an effective mesh material for facilitating the reconstruction of abdominal wall defects and contributed novel design concepts for the surface modification of scaffolds with cell-instructive interfaces and topology.

Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer.

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. STATEMENT OF SIGNIFICANCE: Healing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

An anti-inflammatory chondroitin sulfate-poly(lactic-co-glycolic acid) composite electrospinning membrane for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion is a very common and serious complication, resulting in pain, intestinal obstruction and heavy economic burden. Post-injury inflammation that could activate the coagulation cascade and deposition of fibrin is a major cause of adhesion. Many physical barrier membranes are used to prevent abdominal adhesion, but their efficiency is limited due to the lack of anti-inflammatory activity. Here, an electrospinning membrane composed of poly(lactic-co-glycolic acid) (PLGA) providing support and mechanical strength and chondroitin sulfate (CS) conferring anti-inflammation activity is fabricated for preventing abdominal adhesion after injury. The PLGA/CS membrane shows a highly dense fiber network structure with improved hydrophilicity and good cytocompatibility. Importantly, the PLGA/CS membrane with a mass ratio of CS at 20% provides superior anti-adhesion efficiency over a native PLGA membrane and commercial poly(D, L-lactide) (PDLLA) film in abdominal adhesion trauma rat models. The mechanism is that the PLGA/CS membrane could alleviate the local inflammatory response as indicated by the promoted percentage of anti-inflammatory M2-type macrophages and decreased expression of pro-inflammatory factors, such as IL-1ß, TNF-α and IL-6, resulting in the suppression of the coagulation system and the activation of the fibrinolytic system. Furthermore, the deposition of fibrin at the abdominal wall was inhibited, and the damaged abdominal tissue was repaired with the treatment of the PLGA/CS membrane. Collectively, the PLGA/CS electrospinning membrane is a promising drug-/cytokine-free anti-inflammatory barrier for post-surgery abdominal adhesion prevention and a bioactive composite for tissue regeneration.

Supramolecular Polymer-Nanomedicine Hydrogel Loaded with Tumor Associated Macrophage-Reprogramming polyTLR7/8a Nanoregulator for Enhanced Anti-Angiogenesis Therapy of Orthotopic Hepatocellular Carcinoma.

Anti-angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro-angiogenic factors in the tumor microenvironment (TME) in response to anti-angiogenic therapy, recruiting tumor-associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti-angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX-PMI) co-assembled by anti-angiogenic nanomedicines (PCN-Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs-reprogramming polyTLR7/8a nanoregulators (p(Man-IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN-Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man-IMDQ) NRs repolarize pro-angiogenic M2-type TAMs into anti-angiogenic M1-type TAMs via mannose-binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1-6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2-subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti-angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system-based synergistic approach for tumor therapy.

Skin-Adaptable, Long-Lasting Moisture, and Temperature-Tolerant Hydrogel Dressings for Accelerating Burn Wound Healing without Secondary Damage.

Developing multifunctional wound dressings, possessing not only skin-like mechanical properties and adaptability, long-lasting moisture, and temperature tolerance that maximally mimics the human skin but also on-demand adhesion without unnecessary bleeding and secondary damage upon peeling, is necessary but remains a challenge. Herein, a novel dual cross-linked and multifunctional hydrogel, termed PSNC hydrogel for polymerized sulfobetaine methacrylate (SBMA), N-(2-amino-2-oxyethyl)acrylamide (NAGA), and 1-carboxy-N-methyl-N-di(2-methacryloyloxy-ethyl)methanaminium inner salt (CBMAX), was fabricated as a wound dressing for burn injuries via one-pot radical polymerization in glycerine (GLY)/H2O solvent. The dual cross-linked network of the PSNC hydrogel combined the double hydrogen bonding of N-(2-amino-2-oxyethyl)acrylamide (NAGA) with a covalently cross-linked zwitterionic network, endowing the hydrogel with skin-like mechanical properties with a high stretchability of 1613.8 ± 79.8%, a tensile strength of 77.5 ± 1.8 kPa, and a tensile modulus of 1.9 ± 0.1 kPa. Moreover, the hydrogel with well-developed adaptability can withstand skin deformation without breaking or debonding attributed to its good tissue adhesiveness and self-healing ability. Further, the utilization of the GLY/H2O binary solvent effectively prevented the crystallization and evaporation of free water, endowing the hydrogel with not only long-lasting moisture but also excellent temperature tolerance in a wide range from -20 to 60 °C. More importantly, the PSNC hydrogel could effectively accelerate wound healing of burn injuries and could be easily removed on-demand with saline without causing secondary damage due to intense hydration. Such a novel PSNC zwitterionic hydrogel could be a promising candidate for the treatment of burn wounds and tissue regeneration.

Stability and rupture of archaebacterial cell membrane: a model study.

It is known that the thermoacidophilic archaebacterium Sulfolobus acidocaldarius can grow in hot springs at 65-80 degrees C and live in acidic environments (pH 2-3); however, the origin of its unusual thermal stability remains unclear. In this work, using a vesicle as a model, we study the thermal stability and rupture of archaebacterial cell membrane. We perform a simulation investigation of the structure-property relationship of monolayer membrane formed by bolaform lipids and compare it with that of bilayer membrane formed by monopolar lipids. The origin of the unusually thermal stability of archaebacterial cell and the mechanism for its rupture are presented in molecular details.

Layer-by-layer zwitterionic modification of diverse substrates with durable anti-corrosion and anti-fouling properties.

A versatile coating strategy, which is suitable for the anti-corrosion and anti-fouling modification of chemically distinct substrates, is crucial in many industries. The immobilization of zwitterionic polymers onto the surface has been proven to be an excellent approach for the improvement of antibiofouling potency. However, the anti-corrosion property has not always been considered simultaneously. Herein, a layer-by-layer (LBL) zwitterionic surface modification strategy was proposed: the surface was first coated with a polydopamine (PDA) layer for anti-corrosion; then, by self-assembling a monolayer of 3-aminopropyl triethoxysilane (APTES), the anti-corrosion ability was further enhanced and the efficiency of grafting was improved; thereafter, by immobilizing the zwitterionic polysulfobetaine (PSB) polymer brush layer, the surface could effectively repel biofouling. The surface chemical composition and morphology characterization was performed by using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle measurements, demonstrating that the modification was stepwise introduced onto the surface. The thickness of coating was observed and measured by SEM cross-sectional analysis. In vitro studies revealed that the PSB coated surfaces dramatically reduced the adhesion of bovine serum albumin (BSA), bovine plasma fibrinogen (Fg), bovine γ-globulin (γ-GL), the mixture of these proteins, fibroblasts, E. coli and S. aureus with superior cytocompatibility and hemocompatibility. Moreover, the electrochemical impedance spectroscopy and acidic corrosion studies indicated that an excellent and durable anti-corrosion property was established successfully on the surfaces of stainless steel, cotton textile and wood plates, confirming the feasibility of the LBL surface modification strategy. Significantly, this LBL surface chemistry may be widely applied for the modification of other materials, such as biosensors, biomedical implants and/or devices, and marine equipment.