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The field of medicine has traditionally relied solely on small molecular drugs and conventional surgical procedures. However, recent advancements have shifted the focus toward innovative approaches, such as tissue engineering and regenerative medicine, which aim to overcome the limitations of traditional treatments through personalized and precision medicine. This thesis investigates tissue repair strategies using minimally invasive methods, specifically through the application of injectable biomaterials with or without cell-derived therapeutic factors. To this end, a series of novel injectable hydrogels were developed, alongside protocols for the reliable isolation of extracellular vesicles. These components were then integrated to create injectable therapeutic hydrogels. In Paper I, an injectable collagen-based hydrogel was developed. The injectable hydrogel maintained its shape in aqueous buffers, was biodegradable by the body's own enzymes, and supported the encapsulation and attachment of model cells. In Paper II, the collagen hydrogel from Paper I was further developed for use as a corneal sealant in corneal perforations. The hydrogel retained its beneficial properties of being shape-holding, biodegradable, and supporting cell attachment. Additionally, it exhibited increased transparency and tunable mechanical properties through minor adjustments in stoichiometry. It also successfully withstood burst pressures exceeding normal intraocular pressure levels and demonstrated adhesive properties comparable to fibrin glue, while supporting corneal epithelialization. Altogether, showing promise as an injectable corneal sealant. In Paper III, extracellular vesicles from corneal epithelial cells were isolated, purified and characterized based on their size, morphology, surface protein pattern and protein content. Corneal epithelial extracellular vesicles are thought to promote wound healing which could be confirmed with a functional in vitro scratch assay. These therapeutic EVs were then encapsulated within the collagen hydrogel developed in Paper II. Release studies indicated that while a fraction of the EVs was released by simple diffusion, the majority were released on-demand through enzymatic degradation of the hydrogel. This presents a novel treatment strategy for corneal perforations by combining the tissue adhesive with therapeutic factors. In Paper IV, extracellular vesicles derived from induced pluripotent stem cells (iPSCs) were isolated and shown to promote cardiac function after injury. These EVs were encapsulated in viscous ECM-polymer solutions and injected into the left ventricle of mouse hearts, demonstrating that the viscous polymer solutions enhanced the retention of EVs in cardiac tissue over an extended period.

In summary, this thesis investigates the potential of injectable hydrogels, both alone and in combination with extracellular vesicles, as treatments for corneal and cardiac injuries.