Engineering modular granular hydrogel scaffolds for full-thickness skin and muscle regeneration - PROJECT SUMMARY Soft tissue injuries that effect multiple tissue types, such as full-thickness wounds, present a major clinical challenge due to poor vascularization, inflammation, impaired regeneration, and the treatments capable of supporting multi-tissue regeneration. This project aims to develop a granular hydrogel scaffold (GHS) composed of rod and sphere shaped microgels engineered to guide functional tissue regeneration across complex wound environments. The proposed microgels will be try to mimic critical biophysical and biochemical features of the native extracellular matrix (ECM), providing topographical, mechanical, and chemical cues that can support dermal healing, myoblast alignment, and vascular network formation. The specific aims of this project are: (I) design and fabricate microgels with tunable surface curvature, stiffness, and composition, while also increasing their production, using parallelized microfluidic systems, and to assemble these microgels into complex compartmentalized scaffolds; (II) evaluate cell microgel interactions in vitro including adhesion, viability, alignment, and multicellular organization using fibroblasts, myoblasts, endothelial cells, MSC-HUVEC co-cultures, and differentiated IPSCs; and (III) test GHS efficacy in full thickness murine wound models by assessing tissue integration, neovasculization, and functional healing. To accomplish these objectives microgels will be synthesized using chemically cross linkable biomaterials such as GelMA or chemically modified patient derived ECM polymers (to enhance translatability). Rod shaped microgels will support cell alignment via curvature mediated guidance (curvotaxis), while spheres will be used to promote rapid proliferation and angiogenesis. In vivo outcomes will be measured via imaging, histology, immunostaining, and mechanical testing to evaluate healing quality and scaffold integration. This fellowship will provide enable comprehensive training in biomaterial design, microfluidic fabrication, animal wound models, quantitative imaging, biological assessment, and professional development within a collaborative biomedical engineering environment. The proposed work seeks to improve therapies for complex tissue injuries and introduce an innovative framework for modular biomaterials for soft tissue regeneration.
