Todd D. Johnson

INTRODUCTION: Heart failure following myocardial infarction (MI) impacts millions of people each year in the US. The field of tissue engineering has developed several potential therapies for treating MI including injectable acellular hydrogels. These injectable biomaterials can either be synthetic or naturally derived, and have the potential to be delivered minimally invasively. AREAS COVERED: This review covers the different methods of delivery and presents the initial work on the use of injectable biomaterial scaffolds alone to improve cardiac function post-MI. Several naturally derived materials including alginate, collagen, chitosan, decellularized tissues, fibrin, hyaluronic acid, keratin, and Matrigel, as well as a few synthetic materials have shown promise on their own without the addition of therapeutics such as cells or growth factors. These biomaterials can be potentially delivered via endocardial, epicardial, or intracoronary injections and some can even utilize current catheter technology, indicating a potential for avoiding invasive surgical procedures. Once injected into the wall of the heart, these hydrogels create a scaffold that provides biochemical and structural cues, and the ability for cellular infiltration and remodeling of the local environment. EXPERT OPINION: Injectable biomaterials have several crucial challenges that should be over come to design optimal therapies for MI and heart failure, including optimizing material properties, methods of injection and understanding the mechanisms of action. But, studies in both small and large animals have shown significant improvement in important parameters including wall thickness, vascularization of the ischemic region, left ventricular volumes, and cardiac function. Thus, the application of injectable biomaterials shows promise for developing into new therapies to treat MI, potentially improving millions of lives.

PURPOSE: The purpose of this study was to characterize and quantitatively analyze human cardiac extracellular matrix (ECM) isolated from six different cadaveric donor hearts. EXPERIMENTAL DESIGN: ECM was isolated by decellularization of six human cadaveric donor hearts and characterized by quantifying sulfated glycosaminoglycan content (sGAG) and via PAGE. The protein content was then quantified using ECM-targeted Quantitative conCATamers (QconCAT) by LC-SRM analysis using 83 stable isotope labeled (SIL) peptides representing 48 different proteins. Nontargeted global analysis was also implemented using LC-MS/MS. RESULTS: The sGAG content, PAGE, and QconCAT proteomics analysis showed significant variation between each of the six patient samples. The quantitative proteomics indicated that the majority of the protein content was composed of various fibrillar collagen components. Also, quantification of difficult to remove cellular proteins represented less than 1% of total protein content, which is very low for a decellularized biomaterial. Global proteomics identified over 200 distinct proteins present in the human cardiac ECM. CONCLUSION AND CLINICAL RELEVANCE: In conclusion, quantification and characterization of human myocardial ECM showed significant patient-to-patient variability between the six investigated patients. This is an important outcome for the development of allogeneic derived biomaterials and for increasing our understanding of human myocardial ECM composition.

A comparison of the biochemical, mechanical, and bioactive properties of a porcine myocardial matrix to a new human myocardial matrix and the feasibility of translating this allogeneic hydrogel to the clinic.