UC San Diego

Cardiovascular disease (CVD) is the number one killer in the western world and includes heart failure (HF) after myocardial infarction (MI) and peripheral artery disease (PAD) in the limbs. There is a significant need for developing new therapies to treat patients with these cardiovascular diseases. Recently, the fields of tissue engineering and regenerative medicine have begun to develop naturally derived injectable biomaterials for treating cardiovascular diseases. These naturally derived biomaterials can be derived from a specific tissue's extracellular matrix (ECM) by applying decellularization techniques to either human or non-human tissue sources. This thesis provides crucial steps for the advancement and development of these biomaterials by investigating the importance of tissue specific and species specific sourcing, and investigating a humanized mouse model as a preclinical tool for testing naturally derived biomaterials. Included here is the development of two new human based biomaterials: a human myocardial matrix and a human umbilical cord matrix. The human myocardial matrix (HMM) was used as a tool for investigating allogeneic versus xenogeneic tissue sourcing and for studying the human immune response. The HMM was compared to a porcine myocardial matrix (PMM), which was previously developed as a potential therapy for treating HF after MI. The second material, the human umbilical cord matrix (hUC), was used for investigating the importance of developing tissue specific therapies for treating PAD. Also, the hUC was compared to a porcine skeletal muscle matrix (SKM), which was previously developed as a tissue specific therapy for treating PAD. It was shown in a preclinical animal study that the tissue specific naturally derived material has the potential for producing more desirable clinical outcomes than a non-tissue specific material. In conclusion, this thesis advanced the field of naturally derived biomaterials by presenting the humanized mouse model as a viable tool for preclinical testing and showed the potential for these biomaterials to be used as a therapy for treating PAD