An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure
As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option. However, despite these individual successes, the potential synergistic effect gained by combining the two therapies remains unexplored. This study serves as a translational step in evaluating the minimally invasive delivery of dual acting alginate-based hydrogels to the heart. We have successfully developed new production methods for hybrid alginate/extracellular matrix (ECM) hydrogels. We have identified that the high G block alginate/ECM hybrid hydrogel has appropriate rheological and mechanical properties (1.6 KPa storage modulus, 29 KPa compressive modulus and 14 KPa dynamic modulus at day 1) and can be delivered using a minimally invasive delivery device. Furthermore, we have determined that these novel hydrogels are not cytotoxic and are capable of enhancing the metabolic activity of dermal fibroblasts in vitro (p < 0.01). Overall these results suggest that an effective minimally invasive HF treatment option could be achieved by combining alginate and ECM particles.
KeywordsHeart failure Acellular hydrogel Minimally invasive delivery catheter Alginate Decellularized ECM
AMCARE project funded by European Union’s ‘Seventh Framework’ Programme for research, technological development and demonstration under Grant Agreement no. NMP3-SME-2013-604531.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
- 1.National Heart. Lung, and blood institute (NHLBI) fact book. Fiscal Year. 2012;2012:39–44.Google Scholar
- 3.Braunschweig F, Cowie MR, Auricchio A. What are the costs of heart failure? Europace. 2011;13(sup 2):ii13–7.Google Scholar
- 8.Alraies MC, Eckman P. Adult heart transplant: indications and outcomes. J Thorac Dis. 2014;6:1120–8.Google Scholar
- 14.Curley CJ et al. An in vitro investigation to assess procedure parameters for injecting therapeutic hydrogels into the myocardium. J Biomed Mater Res Part B Appl Biomater. 2016.Google Scholar
- 15.Gaetani, R., Ungerleider, J. & Christman, K.L. In Perin EC, Miller LW, Taylor DA, Willerson JT, editors. Stem cell and gene therapy for cardiovascular disease. Elsevier; 2015. p. 332–348.Google Scholar
- 20.Singelyn JM, Sundaramurthy P, Johnson TD, Schup-Magoffin PJ, Hu DP, Faulk DM, et al. Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction. J Am Coll Cardiol. 2012;59:751–63.CrossRefGoogle Scholar
- 21.Christman K, Singelyn J, DeQuach J. Compositions and methods for tissue repair with extracellular matrices. 2011.Google Scholar
- 22.Christman K, Singelyn J, DeQuach J, Kinsey A. Compositions and methods for cardiac therapy. 2012.Google Scholar
- 35.Rodell CB, Lee ME, Wang H, Takebayashi S, Takayama T, Kawamura T, Arkles JS, Dusaj NN, Dorsey SM, Witschey WRT, Pilla JJ, Gorman JH III, Wenk JF, Burdick JA, Gorman RC. Injectable shear-thinning hydrogels for minimally invasive delivery to infarcted myocardium to limit left ventricular remodeling. Circ Cardiovasc Interv. 2016;9.Google Scholar
- 43.Kafienah W, Sims TJ. Biochemical methods for the analysis of tissue-engineered cartilage. Methods Mol Biol. 2004;238:217–30.Google Scholar
- 46.Melvik JE, Dornish M, Onsoyen E, Berge A, Svendsen T. Self-gelling alginate systems and uses thereof. 2013;1–28.Google Scholar
- 48.Payne C, Dolan EB, O’Sullivan J, Cryan S-A, Kelly HM. A methylcellulose and collagen based temperature responsive hydrogel promotes encapsulated stem cell viability and proliferation in vitro. Drug Deliv Transl Res. 2016;1–15. https://doi.org/10.1007/s13346-016-0347-2LBPayne2016.
- 49.Dolan EB, Kovarova L, O’Neill H, Prvada M, Sulakova R, Scigalkova I, et al. Advanced material catheter (AMCath), a minimally invasive endocardial catheter for the delivery of fast-gelling covalently cross-linked hyaluronic acid hydrogels. J Biomater Appl. In Publication (accepted 19/09/18). 2018;25:088532821880587.Google Scholar
- 57.Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials. 2006;27:3675–83.Google Scholar