Characterization and release modelling in ELR-based nanocomposite hydrogel loaded with polylactic acid for the implementation of a biomedical device

Abstract

Cardiac tissues are difficult to regenerate due to the low proliferative capacity of cardiomyocytes. A new ther- apeutic strategy for cardiac regenerative medicine could include a device capable of ensuring cell grafting, stimulating cardiac tissue regeneration, and serving as an appropriate scaffold for the controlled and sustained release of lactate over time as an inducer of cardiomyocyte proliferation. An effective source of lactate could consist of the lactic acid polymer (PLA) itself, which generates free lactic acid during its degradation. In this work, we have developed a nanocomposite hydrogel for lactate release based on a biocompatible and biode- gradable matrix formed by elastin-like recombinamers cross-linked via click chemistry. Polylactic acid particles were encapsulated in the matrix after these particles had been partially degraded to lactic acid through oxygen plasma treatment. In the first 48 h, an early and modulated release of free lactic acid from plasma-treated PLA degradation is observed, and over longer periods, a sustained release of lactic acid produced by the hydrolytic degradation of PLA under physiological conditions occurs. Lactate is available from the very beginning (“early release”), addressing the drawback of the slow degradation (by hydrolysis) of polylactic acid. Therefore, a biomedical device has been designed and implemented, formed by an ELR polymeric matrix as an analogue of cardiac tissue, acting as a device for early, controlled, and sustained lactate release, with dosing at concentrations similar to those previously studied as suitable for promoting cardiomyocyte proliferation, showing promise for its use in the regeneration of infarcted cardiac tissue.