An injectable double cross-linked hydrogel adhesive inspired by synergistic effects of mussel foot proteins for biomedical application.

Hydrogel adhesives with high tissue adhesion, biodegradability and biocompatibility are benefit for promoting surgical procedures and minimizing the pain and post-surgical complications of patients. In this paper, an injectable mussel inspired double cross-linked hydrogel adhesive composed of thiolated mussel inspired chitosan (CSDS) and tetra-succinimidyl carbonate polyethylene glycol (PEG-4S) was designed and developed. CSDS was synthesized with thiol and catechol groups inspired by the synergistic effect of mussel foot proteins (mfps). The double cross-linked hydrogel was first formed by the addition of sodium periodate (or Fe3+) and then double cross-linked with PEG-4S. The results showed that the mechanical and adhesion properties of the double cross-linked hydrogels were significantly improved by the synergistic effects of the functional groups. And the prepared hydrogels showed good cytocompatibility which evaluated by determining the viability of L929 cells and human umbilical vein endothelial cells (HUVECs). Additionally, the biodegradability and biocompatibility in vivo were further confirmed by subcutaneous implantation in mice model, and the histological analysis results identified that the prepared hydrogels were in vivo biocompatible. This work presents an injectable mussel inspired double cross-linked hydrogels that can use as a potential hydrogel adhesive for biomedical application.

Nanofibrous vascular scaffold prepared from miscible polymer blend with heparin/stromal cell-derived factor-1 alpha for enhancing anticoagulation and endothelialization.

There is an urgent clinical demand to develop a functional small diameter vascular graft with long-term patency, which mainly relies on the anticoagulation and endothelialization of the vascular graft. In addition, improved degradation of vascular graft provides more space for cell infiltration and facilitates remodeling of blood vessel. In this study, an elastic and biomimetic nanofibrous vascular scaffold with improved degradability was prepared by adding poly(lactic-co-glycolic acid) (PLGA) into the poly(L-lactic acid) (PLLA)/poly(L-lactide-co-ε-caprolactone) (PLCL) blend using thermally induced phase separation (TIPS) technique. The incorporation of PLGA also improved the hydrophilicity of the composite scaffold. Then the vascular scaffold was surface modified by combination of heparin and stromal cell-derived factor-1 alpha (SDF-1α). The results of whole blood clotting kinetics and plasma recalcification profiles indicated that heparinized modification significantly enhanced the anticoagulation of vascular scaffold. In vitro cell culture assays demonstrated the immobilized SDF-1α facilitated recruitment of endothelial progenitor cells (EPCs), migration and proliferation of mature endothelial cells, human umbilical vein endothelial cells (HUVECs), and expression of VE-cadherin/CD144 and endothelial nitric oxide synthase (eNOS) genes in HUVECs, thereby accelerating the endothelialization of the modified vascular scaffold. Besides, the nanofibrous vascular scaffold modified with heparin and SDF-1α inhibited the proliferation of human vascular smooth muscle cells (HVSMCs). Therefore, the phase separated nanofibrous vascular scaffold modified with heparin and SDF-1α shows the promising in vitro performance as a functional small diameter vascular graft.

Enhanced biocompatibility of poly(l­lactide­co­epsilon­caprolactone) electrospun vascular grafts via self-assembly modification.

Thousands of coronary artery bypass surgeries are performed in the world every year. But there is still no alternative to autologous vessel transplantation yet. In the present study, we optimized the weight ratio of chitosan/poly(l­lactide­co­epsilon­caprolactone) (CS/PLCL) of the electrospun scaffolds, which lead to suitable mechanical properties, such as tensile strength, ultimate strain, elastic modulus and burst pressure. Besides, the scaffolds possessed the structure that mimics the native extracellular matrix. To improve the anticoagulant property of vascular grafts and avoid the use of toxic reagents, dextran sulfate was used to modify the scaffold by self-assembly method. The result of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) demonstrated the successful modification of dextran sulfate on the scaffold. Simultaneously, modification with dextran sulfate enhanced the hydrophilicity of the scaffold. Then the degradation property of the scaffolds was evaluated by the pH value of the phosphate buffer solution (PBS) soaking solutions and mass loss of the scaffolds. Hemocompatibility test was then performed to determine the enhanced anticoagulation and antihemolysis properties of the modified scaffold. The in vitro cell viability results showed that the modified scaffold possessed favorable cell viability to the human vascular cells. Furthermore, the scaffolds were subcutaneously implanted in mice for 4 weeks. Compared to the unmodified and pure PLCL tubular scaffolds, the histological analysis indicated that the modified tubular scaffolds possessed low inflammatory response and more infiltrated cells in the scaffold. Therefore, our studies showed that dextran sulfate modified scaffold might pave the way to fabricate small-diameter vascular grafts for clinical application.

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique.

INTRODUCTION: The fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(L-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique. MATERIALS AND METHODS: The miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells' infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied. RESULTS: PLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells' infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation. CONCLUSION: This study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering.