Dynamic Biomaterial Platforms for Controlled Delivery of Cell-Free Therapeutics in Women’s Health

Pelvic organ prolapse (POP), a debilitating condition affecting millions globally, results from weakened pelvic floor tissues causing organ descent. Current surgical treatments using synthetic meshes face high failure rates and complications, necessitating innovative regenerative strategies that combine mechanical support with biological repair. This project develops hydrogel-based platforms for the sustained delivery of cell-free therapeutics, including extracellular vesicles (EVs) and oligonucleotides, to address POP and related gynecological conditions. Therapeutic agents such as mesenchymal stem cell-derived EVs demonstrate regenerative potential but face challenges in rapid clearance and instability in vivo. Hydrogels offer customisable biomaterial systems to overcome these limitations through controlled release and protection of therapeutics. This research expands beyond EVs to explore oligonucleotide delivery for targeted gene regulation and exosomes for enhanced paracrine signalling, creating a versatile platform for diverse cell-free approaches. The central hypothesis proposes that hydrogel systems optimised for spatiotemporal control of therapeutic release will enhance tissue regeneration and functional recovery. Key aims include hydrogel formulation with tissue-mimetic mechanical properties, therapeutic loading optimisation, in vitro bioactivity assessment, and in vivo efficacy evaluation in animal models. Technical methodologies integrate advanced biomaterial characterisation (tensile studies) with therapeutic analysis. For EVs, isolation employs ultracentrifugation and size exclusion chromatography, complemented by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Oligonucleotide delivery systems will leverage chemically modified hydrogels for nucleic acid stability, while exosome studies include cargo profiling via RNA sequencing and proteomics. Functional assays assess therapeutic effects on collagen synthesis, matrix remodelling, and cellular recruitment. This multidisciplinary project bridges regenerative medicine, biomaterials engineering, and women’s health. Participants will gain expertise in hydrogel design, therapeutic encapsulation strategies, and translational evaluation across in vitro and preclinical models. The platform’s modularity supports broader applications in pelvic floor disorders, advancing cell-free therapeutic delivery for improved clinical outcomes.