GEMGEL · A biomimetic zonally gene-activated load-bearing reinforced hydrogel for meniscus repair

Meniscal tears are the most prevalent injuries of the knee joint and a major contributing factor to osteoarthritis (OA) development. Current treatments cannot effectively repair meniscus and only delay the onset of OA. Tissue engineering and regenerative medicine (TERM) approaches aim to promote the regenerative capacity of the tissue; however, this is hindered by the challenges of replicating the complex microenvironment of the tissue coupled with its intrinsic avascularity. My overarching aim is to develop an innovative zonal load bearing scaffold through melt electrowriting optimised using a machine learning approach to mimic meniscus biomechanics and extra cellular matrix (ECM) architecture. This will be integrated with corresponding zonal gene activated hydrogels using transcription factors implicated in meniscus regeneration to induce intrinsic regenerative capabilities. Prof. Khademhosseini (Terasaki Institute; outgoing phase), has extensive experience in hydrogels, 3D printing and stem cells. I will develop a 3D layered microfibre reinforced hydrogel scaffold mimicking the collagen architecture, biochemical and biomechanical properties of the meniscus and test its biological performance using human stem cells. Prof. Fergal O’Brien (RCSI; return phase), has extensive experience in scaffold-mediated gene therapy, particularly for musculoskeletal applications. Using techniques established in his group, I will develop zonally gene-activated scaffolds that can be used as a local delivery system in a radically new regenerative therapy for meniscus tears. Under the supervision of Prof. O’Brien and Khademhosseini, who will guide my Career Development Plan, I will develop key complementary skills in project management, entrepreneurship, commercialization, dissemination and leadership. These, along with advanced research competencies, will help me become an independent scientist, enhancing my visibility and competitiveness in in the TERM field.