| Polyurethane materials are block copolymers formed by alternately connecting soft and hard segments,which have excellent structural controllability and distinct microphase separation structures.Bio-based polyurethane with biomass materials introduced,has excellent biocompatibility and shows huge application potential in many fields,such as wound dressings,tissue patches,and tissue scaffolds.However,the existing design strategies for bio-based polyurethane make the materials poor in bioactivity,lack in-depth exploration of biocompatibility during degradation,moreover,the primitive strategies for constructing composite networks make the materials poor in tissue repair and regulation functions,leading to unexpected therapeutic effects.Therefore,the functional design of bio-based polyurethane and the structural construction of composite systems are of great significance for the application of bio-based polyurethane in the field of medical research.Based on the above issues,in this research,two functional bio-based polyurethane molecules were designed and synthesized using bioactive materials such as L-arginine and L-cysteine,and their biodegradability,biocompatibility,and tissue regulatory activity were systematically studied as well.Therefore,in this study,the dual network composite system constructed by functionalized bio-based polyurethane and biomacromolecules,such as modified gelatin,modified chitosan and bacterial cellulose.The novel bio-based polyurethane composites with biological activity and regulatory effect on tissue repair were prepared,displaying excellent practical application performance of materials in the fields of acute tissue bleeding,chronic wound care,cartilage microenvironment regulation and tissue patches,providing important theoretical and data support for the clinical application of bio-based polyurethane.(1)L-Arg,biodegradable PEG and IPDI,which have excellent biocompatibility and promoting wound healing,are used to synthesize arginine terminated highly adhesive bio-based polyurethane DLPU.The multifunctional double network hydrogel G-DLPUs was constructed by compounding it with modified gelatin GelMA.The properties of the bio-based polyurethane dual network system with different proportions were studied comprehensively.In addition,the adhesive properties of the composite materials at different materials’dry and wet interfaces can reach 100 KPa,confirming its great application potential in adhesion and hemostasis.Through in vitro biodegradability testing,it was confirmed that the biodegradable polyurethane did not lead to uncontrolled pH in the microenvironment during the degradation process,and the excellent biocompatibility of the degradation solution was confirmed as well.After studying the ability of L-Arg in degradation solution to promote the release of NO from cells and its biocompatibility in vivo,the evaluation of the practical application performance of G-DLPU3 was conducted comprehensively using a mouse skin fullthickness defect model and a rat liver bleeding model.The results showed that GDLPUs can effectively promote wound healing and reduce wound bleeding(reduce bleeding by 71.5%).(2)Using anti-inflammatory L-cysteine(L-Cys)and β-Cyclodextrin(β-CD)and other raw materials to synthesize bio-based polyurethane with anti inflammatory and drug loading properties.The functionalized biphase gel dressing HAB gel(LPU/PVA PAMs)was constructed by compounding it with polyvinyl alcohol grafted with polyacrylamide.The properties of bio-based polyurethane dual network systems with different proportions were studied comprehensively,including mechanical properties,surface roughness,water absorption(1510%)and water retention(91%).By loading green antibacterial agent PHMB with β-CD,the biphase gel was endowed with more than 72-h efficient antibacterial properties.HAB-gel was tested with L929 and red blood cells,respectively,and the results showed that the composite had excellent L929 cell compatibility and red blood cell compatibility.Further,the performance of HAB-gel material as a chronic wound dressing was evaluated using a mouse symmetrical full-thickness skin defect model,and the results showed that;HAB-gel has better wound healing properties than commercial 3M dressings,and the composite can induce the polarization of macrophages around the wound from M1 to M2 subtype,demonstrating significant anti-inflammatory properties.(3)Endowing with pH regulating in microenvironment,the porous cartilage scaffolds with dual network structure(M-APUs)was obtained by compounding Arginine-based polyurethane(APU)with methacrylic chitosan(MC)through interactions of hydrogen bonds and ion bonds between molecules.The controllable degradability of M-APUs was evaluated systematically,including the biocompatibility and the pH stability durring the degradation process,verifying the significant microenvironment pH stabilization(7.10～7.31)of the composite system.The adhesion and migration experiments of bone marrow stem cells on the surface of M-APUs have verified,and the results showed their recruitment effect on stem cells in cartilage defects.The microenvironment pH regulation of M-APUs cartilage scaffolds and their cartilage repair promoting properties after recruitment of stem cells was conducted and evaluated systematically using a rat knee cartilage defect model.The results showed that M-APUs had significant anti-inflammatory and cartilage repair promoting effects,specifically manifested in inducing the polarization of subchondral bone macrophages into an anti-inflammatory phenotype,promoting the synthesis of cartilage matrix,and ultimately achieving improved integrity of the bone cartilage interface and significant recovery of joint function.(4)The dual network tissue patch(BC/LPU-MCs)with anti-adhesion property and high mechanical properties was obtained by compounding L-cysteine based polyurethane(LPU)and methacrylic chitosan(MC)on bacterial cellulose membrane(BC)after conducting a "click reaction" between the thiol group of the bio-based polyurethane and the double bonds in modified chitosan on the BC fiber network.The PU-MC coating embedded on the BC fiber network in the composite(BC/LPU-MCs)can effectively regulate the hydrophobicity and surface roughness of the patch material.Through evaluating the mechanical properties of patch materials systematically,it was found that they have excellent tensile strength(213.9 MPa),suture strength(3.18 N),and bursting strength(98.1 N).The significant anti-adhesion effect was verified by fibroblast experiments.Finally,the medical application potential of the tissue patch was evaluated by performing as a hernia patch using an animal model of rat.The results shown that the tissue patch has excellent anti-adhesion properties and significantly promoting peritoneal tissue repair,such as after 12-week treatment,the integrity of the peritoneum reached 95.2%,vascular density and collagen deposition were improved significantly. |
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