Development of a nanocomposite substrate with two unique surface properties, cell attachment and protein anti-adsorption

Implants are placed inside human body to perform specific functions in the body system. However, implants cause unwanted nonspecific protein adsorption that might lead to chronic inflammatory reactions, pain, seroma, infection, adhesion (especially for hernia repair by mesh), rejection, and further complications. Low protein adsorption and cell attachment and proliferation are two promising concepts to enhance biocompatibility in implants for minimum immune response and normal healing. Fibre-based biomaterials hold the promise to address these issues by providing different properties on each side of implants to facilitate their contact with intestines or body fluids and promote healing stimulation for damaged tissues. This research aims to develop an implantable nanocomposite substrate (hernia mesh) with dual-sided biocompatibility characteristics for protein anti-adsorption and high cell attachment and proliferation, respectively, one on each side. To address the issue of protein adsorption, a zwitterionic protein anti-adsorption monomer- 2-methacryloyloxyethyl phosphorylcholine (MPC) was grafted on a polypropylene (PP) mesh after plasma-activation via optimized Ultraviolet (UV)-irradiated graft polymerisation. The as-developed mesh was characterised by attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM),  energy-dispersive X-ray (EDX), water contact angle, and its properties were evaluated by protein adsorption assay and cell study. Poly(2 methacryloyloxyethyl phosphorylcholine) (PMPC) grafting on mesh resulted in a significant reduction in water contact angle (0º), bovine serum albumin (BSA) protein adsorption (⁓ 97%) and L929 cell attachment while maintaining nontoxicity with ∼ 90% cell viability. Based on these promising results, this modified hernia mesh is expected to show improved biocompatibility with reduced adhesion problem in real life application. Chitosan was selected for surface modification of PP for enhancing cellular response and antimicrobial properties. The suitable method and parameters of applying chitosan on mesh were optimised. As an antibacterial agent, functionalised nanodiamond (FND) with hydroxyl groups was combined with chitosan on the surface of a mesh. The as-developed mesh was characterised by ATR-FTIR spectroscopy, SEM, water contact angle, and its properties were evaluated by bursting strength test, anti-microbial assay, degradation, and cell study. The modified mesh retained its mechanical strength (at curing up to 130 ºC) and chemical structure after 7 days of degradation in Dulbecco's phosphate-buffered saline (DPBS). A significant increase in hydrophilicity (n = 7, p < 0.05), fibroblast cell attachment (134%) and microbial resistance was evident for the modified mesh (PP-Chi-FND) with low concentration of FND. Therefore, this modified mesh is expected to sustain in the hostile body environment after implantation and facilitate healing by promoting cell attachment and proliferation at the wound site. Finally, based on the as-developed parameters of this project, a dual-sided mesh was developed with Chi/FND on one side and PMPC on the other side of the mesh by a novel semi-solid polymer mould (SSPM) method. The dual-sided mesh showed completely different hydrophilicity and cellular responses on each side, with a 96% reduction in BSA protein adsorption as compared to the PP mesh. Replacing the FND with a novel magnesium hydroxide nanoparticle has further improved the antimicrobial property of the dual-sided mesh against strong methicillin-resistant Staphylococcus aureus (MRSA) bacteria without hampering dual-sided properties. Therefore, this dual-sided mesh with improved biocompatibility and antimicrobial property is expected to address the common issues, including lack of biocompatibility, unwanted adhesion, poor healing, infection and their related complications with the commercial hernia mesh. The development of a dual-sided mesh is very promising for its application in hernia surgery so that the parietal side (facing the incision wound) can provide healing stimulation and the visceral side show no cell attachment to avoid unwanted adhesion to the intestine. Here, a novel method was developed to modify surfaces differently imparting various properties without hampering its porosity. This will not only facilitate its specific use as a hernia mesh but also open new opportunities for other applications of porous implants.