BS43 Pro-angiogenic injectable self-assembling peptide hydrogel as a delivery vehicle for cardiac cell therapies

• Published in: Heart (British Cardiac Society) Vol. 108; no. Suppl 1; pp. A171 - A172
• Main Authors: King, Katharine, Cartwright, Elizabeth, Oceandy, Delvac, Zi, Min, Facchi, Cecilia, Njegic, Alexandrea
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Cardiovascular Society 06.06.2022; BMJ Publishing Group LTD
• Subjects: Angiogenesis; Basic science; Biomaterials; Cardiac function; Cardiomyocytes; Heart; Hydrogels; iPSC; Peptides; Stem cells
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/heartjnl-2022-BCS.223

IntroductionCardiac cellular therapies offer a potential solution to restore cardiomyocyte populations post myocardial infarction (MI). However, when injected directly into the diseased heart only 1% of cells survive due to mechanical displacement and the ischemic nature of the heart post MI. Innovations in bioengineering have led to the development of hydrogel scaffolds to hold the cells in place and provide a structural platform to support new tissue formation. Beyond physically holding the transplanted cells in place, the ideal hydrogel scaffold would boost new blood vessel development to provide vascular support for the transplanted cells. In this study we aim to develop a pro-angiogenic, injectable self-assembling peptide hydrogel (SAPH) which augments the sprouting and migration of endothelial cells. We will also look at the effect of intra-cardiac injection of SAPHs on healthy myocardium to validate it as a delivery vehicle for cells in cardiac cell therapies.MethodsAlamar blue and live/dead assays were used to assess the compatibility of Human Umbilical Vein Endothelial Cells (HUVECs) with SAPHs made up of different peptide sequences. Integrin binding motifs RGD, IKVAV, YIGSIR and GFOGER were then added to the peptide and a 3D sprouting assay was used to quantify the effect of the different integrin binding motifs on HUVEC migration and sprouting. To validate the SAPHs as a cardiac cell therapy delivery vehicle 10μl of SAPH was delivered via intra-cardiac injection into the left ventricle of Balb/c mice. A range of parameters were then used to assess cardiac function post gel injection.ResultsTwo different SAPHs, Alpha 2 and Alpha 4, were chosen from Manchester BIOGEL due to their slow degradation kinetics and comparable stiffness to heart tissue (10 kPa and 1 kPa respectively). We found that Alpha 4 was able to support the 3D culture of HUVECs and therefore was used as the base peptide for the addition of different integrin binding motifs. A spheroid based sprouting assay showed Alpha 4 with the combined addition of GFOGER and RGD integrin binding domains increased sprouting and migration of ECs into the hydrogel. We have also shown that the SAPH can be safely delivered to the hearts of mice and remain in situ with no negative effects on cardiac function. Finally, induced pluripotent stem cell derived cardiomyocytes are highly compatible with 3D culture within Alpha 4. We have shown they can be cultured for at least 3 weeks and exhibit the spontaneous beating behaviour within the gel.ConclusionAlpha 4 with the addition of GFOGER and RGD is a promising biomaterial for the delivery of cells such as induced pluripotent stem cell derived cardiomyocytes to the heart post MI.