Melt electrowriting
(MEW) is an additive manufacturing technology
that produces readily handleable fibrous scaffolds with controlled
geometry to support cell infiltration. Although MEW scaffolds have
excellent potential for cell delivery in regenerative medicine applications,
studies to date have primarily focused on polymers such as poly(ε-caprolactone)
(PCL) that lack bioactive cues to affect cell function. To address
this aspect, MEW scaffolds with extracellular matrix (ECM) coatings
were developed as a proadipogenic platform for human mesenchymal stromal
cells (hMSCs). More specifically, highly flexible PCL scaffolds fabricated
through MEW were coated with a complex ECM suspension prepared from
human decellularized adipose tissue (DAT), purified fibronectin, or
laminin to determine the effects of two key bioactive proteins present
within adipose-derived ECM. In vitro studies exploring the response
of human bone marrow-derived mesenchymal stromal cells cultured under
adipogenic differentiation conditions indicated a high level of differentiation
on all substrates studied, including unmodified PCL scaffolds and
two-dimensional controls. To more fully assess the intrinsic proadipogenic
capacity of the composite biomaterials, a modified culture regime
was established that involved a short-term adipogenic induction in
differentiation medium, followed by continued culture in maintenance
medium supplemented with insulin for up to 3 weeks. Under these conditions,
adipogenic differentiation was enhanced on all fiber scaffolds as
compared to the tissue culture controls. Notably, the highest adipogenic
response was consistently observed on the PCL + DAT scaffolds, based
on the analysis of multiple markers including adipogenic gene [lipoprotein
lipase, fatty acid binding protein 4 (FABP4), adiponectin, perilipin
1] and protein (FABP4, leptin) expression and intracellular triglyceride
accumulation. Taken together, the PCL scaffolds incorporating DAT
provide an adipoinductive microenvironment for the hMSCs, with particular
applicability of this cell-instructive delivery platform for applications
in plastic and reconstructive surgery.