Executive Summary : | Antibacterial resistant infections and inadequate osteointegration are extremely unfortunate factors for the failure of implants in post-orthopaedic surgery. Implant failures add to the burden of public health costs, painful revisions, and the unavoidable implant removal. They may cause morbidity, which can be life-threatening. Globally, there is an estimation of the failure rate of implants at approx. 20% and 5% due to lack of osteointegration and infections, respectively. To address these issues, many strategies were used to improve the anti-infection property by organic, inorganic, and antimicrobial peptides, whereas to improve osteointegration by bioactive coatings, growth factors and peptides. However, these affect the bone microenvironment in terms of toxicity, uncontrolled release of bioactive agents, and other drawbacks like higher cost, and complicated bench-to-bedside processes. Advanced additive manufacturing has recently been employed to develop patient-specific porous 3D implants to overcome these obstacles. However, they may encounter the osteointegration problem but do not address the infections and challenges for clinician practice, limiting their extensive clinical adaptation. To date, there has yet to be a reliable, effective, and affordable technology to simultaneously stimulate the rapid osteointegration and anti-infection of implants. Henceforth, there is an imperative need to develop biofunctional integrated implants with parallel abilities to minimize the risk of infection and encourage biointegration. Therefore, this project aims to develop a new generation of cell-laden 3D-hydrogel layered coatings on orthopeadic implants with no other bactericidal agents, inorganic materials, and bone-induced small molecules. This project work will be advanced over previous research attempts in aspects of: (i) Ti alloy surfaces will be activated with plasma-induced acrylic acid polymerization to engage the strong adhesion of hydrogel coatings; (ii) 3D bioprinting of bilayer cell-laden hyaluronic acid (HA) and bifunctional chitosan (CsMAP) hydrogels will be combined with sPAAC click chemistry (strain-promoted alkyne-azide cycloadditions) to stipulate robust intra-layer binding stability, and provide a microenvironment for faster cellular communications. (iii) HA hydrogel will be loaded with mesenchymal stem cells to promote rapid biointegration, and (iv) the CsMAP hydrogel will impart intrinsic bactericidal activity to reduce infections while also promoting bone mineralization and integration. This new generation of 3D bioprinting-assisted click chemistry-induced layered hydrogel coatings on implants will alleviate bacterial infections while providing a bio-microenvironment for de novo bone tissue integration. The successful outcomes of this project will shed light on bone-to-implant interactions, assisting in the development of better bone health solutions and new sustainable orthopaedic implants for long-term clinical success. |