A new hybrid bioartificial shape memory hydrogel for the anastomosis of human hollow organs

摘要

Introduction: A large number of pathologies require the resection of the bowel and anastomoses to rejoin the two remaining stumps to regain lumen patency. Various materials have been used to rejoin one bowel end to the other like catgut, stainless steel. The actual method uses entero-entero anastomosis circular stapler with only a staple line showing some possible drawbacks, like intracellular fluid leakage and local inflammation. The aim of this study is to develop a novel bioartificial device with a ring shape based on polyvinyl alcohol and gelatin loaded both directly with acetylsalicylic acid (PVA/Gel/Asa) and with acrylate nanoparticles incorporating the same drug (PVA/Gel/Asa Asa-Nps) to reduce possible local inflammation also at prolonged times. Materials and Methods: PVA and gelatin was blended at 80/20 weight ratio. A physical method with 8 cycles freezing/thawing was used to obtain a crosslinked bioartificial shape memory ring. Asa at maximum solubility concentration, and Nps loaded with Asa were simultaneously incorporated during hydrogel preparation. The physicochemical characterization was performed by equilibrium swelling degree (EDS) evaluation and FT-IR Chemical Imaging. Elastic modulus was studied by DMA in compression mode. HPLC was used to evaluate Asa release kinetics. Cell culture tests were performed to evaluate cell adhesion and proliferation onto the hydrogel. Results: FT-IR spectrum allowed to detect the principal bands associated to bioartificial composition and the presence of molecular interactions between two components. EDS values of 215% for PVA/Gel Asa-Nps and of 214% for PVA/Gel after 6 days were measured. The mechanical properties showed for PVA/Gel/Asa Nps-Asa a storage modulus of 1.0 MPa. Drug release from Asa-Nps, PVA/Gel/Asa and PVA/Gel/Asa Asa-Nps was 8.4%, 51.9%, 54.9% (w/w), respectively. Discussion: Agood chemical homogeneity of the bioartificial hydrcgel components was registered by FT-IR. The addition of gelatin increased the hydrophilicity of PVA-based hydrogels moving EDS value from 160 to 215%, while the loading with Nps seemed to not influence EDS (214%). Mechanical analysis showed a storage modulus of hydrogel system in good agreement with the value reported for human colon. A rapid release of Asa at the initial phase and a subsequent prolonged delivery was observed allowing obtaining a drug release both immediately after the anastomosis surgery and during the healing period. Importantly, functional tests demonstrated the water induced shape memory performance of hydrogel. Preliminary cell culture tests using human dermal fibroblasts indicated the cytocompatibility of the hydrogel. Conclusions: In this work, a bioartificial hydrogel was developed for the first time to reduce the local inflammation occurring after anastomosis surgery on the human hollow organs. Overall, the results obtained suggest the potential of this hydrogel to serve as an efficient drug targeting anastomotic device.