Heparin-binding domains in elastin-like proteins: a way towards improved tissue integration?

Abstract

A heart attack leads to irreversible damage to the heart muscle. Current treatment methods primarily focus on preventing secondary infarcts but do not address the sustained tissue damage. Consequently, a myocardial infarction often initiates an unfortunate chain of events leading to the development of cardiac arrhythmias and ultimately heart failure. New stem cell therapies are under development, but their effectiveness is limited by the poor retention of these cells at the infarct site. As a result, the majority of injected cells do not have ample time to differentiate into functional cardiomyocytes. Injectable hydrogels provide an effective approach to enhancing stem cell retention. Elastin-like proteins (ELPs) have a long history in this field due to their intrinsic lower critical solution temperature (LCST).1 In this contribution, we describe the design and biotechnological production of recombinant ELPs incorporating heparin-binding domains (HBDs). HBDs are a class of positively charged peptide domains that have been previously studied as an affinity tag in protein purification. The expected interaction of these peptide domains with negatively charged components of the extracellular matrix (ECM), such as hyaluronic acid and sulphated glycosaminoglycans (GAGs), is hypothesised to contribute to improved tissue integration of the stem cell carrier. In this presentation, we describe the optimised expression parameters, the validation of the proteins’ LCST behaviour and their preliminary biocompatibility assessment. Finally, the ELPs' interaction with negatively charged ECM components was studied via lap shear tests.