Development and characterization of matrix-derived microcarriers from decellularized tissues using electrospraying techniques.

Abstract

Stirred bioreactor systems integrating microcarriers represent a promising approach for therapeutic cell manufacturing. While a variety of microcarriers are commercially available, current options do not integrate the tissue-specific composition of the extracellular matrix (ECM), which can play critical roles in directing cell function. The current study sought to generate microcarriers comprised exclusively of ECM from multiple tissue sources. More specifically, porcine decellularized dermis, porcine decellularized myocardium, and human decellularized adipose tissue were digested with α-amylase to obtain ECM suspensions that could be electrosprayed into liquid nitrogen to generate 3D microcarriers that were stable over a range of ECM concentrations without the need for chemical crosslinking or other additives. Characterization studies confirmed that all three microcarrier types had similar soft and compliant mechanical properties and were of a similar size range, but that their composition varied depending on the native tissue source. In vivo testing in immunocompetent mice revealed that the microcarriers integrated into the host tissues, supporting the infiltration of host cells including macrophages and endothelial cells at 2 weeks post-implantation. In vitro cell culture studies validated that the novel microcarriers supported the attachment of tissue-specific stromal cell populations under dynamic culture conditions within spinner flasks, with a significant increase in live cell numbers observed over 1week on the dermal- and adipose-derived microcarriers. Overall, the findings demonstrate the versatility of the electrospraying methods and support the further development of the microcarriers as cell culture and delivery platforms.