Towards expanding versatility of extracellular matrix hydrogels

This project aims to develop a new class of paint-like bioadhesive materials that can be directly applied to injured or damaged soft tissues. These materials are inspired by the natural adhesion mechanisms of mussels and are designed to adhere to wet biological surfaces, conform to complex shapes, and promote tissue healing. A unique aspect of this work is the use of biological matrices derived from decellularized tissues that are rich in biological factors that support cell growth and tissue regeneration. The project will compare different formulations based on naturally occurring adhesive molecules combined with biopolymers to create a flexible, easy-to-apply platform for regenerative therapies. The technology has broad potential to impact multiple areas of medicine, such as wound healing and organ regeneration. The project will also provide interdisciplinary training to Arkansas K-12, undergraduate, and graduate students in biomaterials, tissue engineering, and biofabrication, thereby advancing education and workforce development in biomedical engineering. This project will advance our understanding of design criteria for paintable formulations of decellularized tissue extracellular matrix (dECM) cocktails. Current dECM formulations and the biologics derived from these materials are limited in their therapeutic potential for tissue repair and regeneration due to challenges with post-operative adhesions and insufficient mechanical strength. Our proposed paintable dECM formulations have the unique capability to overcome these limitations by offering bio-adhesive properties to wet surfaces enabling minimally invasive placement onto delicate or irregular tissues where traditional scaffolds/patches are impractical. By leveraging catecholamine chemistries with naturally derived polymer backbones via both enzymatic and chemical crosslinking approaches, this work will generate formulations with strong adhesion, rapid polymerization, and in vivo biocompatibility. Further, the use of decellularized tissues from the nervous system including ECM-rich sciatic nerve and proteoglycan-rich spinal cord as starting materials harbors vast untapped potential for widespread use in regenerative medicine. The paint formulations will be optimized, and structure-function relationships will be assessed in vitro and in vivo through subcutaneous implants. The fundamental underpinnings that will be learned through this work will enable a new class of biomaterials that will transform applications in tissue engineering and beyond. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.