Design and Characterization of Tissue-Specific Extracellular Matrix-Derived Microcarriers

The three-dimensional (3D) extracellular matrix (ECM) environment plays a critical role in mediating normal cellular behavior and tissue organization. While commercially available microcarriers have shown promise, limited research has been conducted on the design of tissue-specific, custom-fabricated microcarriers, engineered to mimic the composition of the native ECM of cells or tissues of interest. Moving toward this goal, methods were developed to fabricate microcarriers from decellularized adipose tissue (DAT) via minimally-cytotoxic protocols. Characterization by microscopy confirmed the production of stable spherical microcarriers, with a microporous surface topography and porous interior. The mean diameter of the DAT microcarriers was 934 +/- 51 mu m, while the porosity was estimated as 29% +/- 4% using liquid displacement. Stability and swelling behavior over 4 weeks indicated that the DAT microcarriers were effectively stabilized with the photochemical crosslinking agent rose bengal, with total protein release in a simulated physiological environment remaining below 10 mu g/mL at all time points. Preliminary cell culture studies with human adipose-derived stem cells (ASCs) in a spinner flask system indicated enhanced cell attachment and proliferation of ASCs on DAT microcarriers over 14 days, as compared with gelatin control microcarriers fabricated using similar methods. Testing confirmed injectability of the DAT microcarriers, further supporting the clinical potential of the approach for localized cell delivery and small volume augmentation in plastic and reconstructive surgery. Overall, tissue-specific microcarriers prepared from solubilized DAT were found to be highly supportive of human ASCs cultured in a 3D dynamic environment.