There is a compelling need for the development of coating materials that mimic the native cellular microenvironment for better in vitro
assays and for the expansion of cells for cell-mediated therapies. In addition, a culture platform where cells are surrounded by an environment that more closely resembles the native ECM niche would improve the assessment of cell behavior in other areas of research such as drug development applications. There has been a shift of cell culture substrates from single purified proteins, to more complex materials that attempt to mimic the complex native ECM 
. Combinations of purified proteins have been shown to improve cell proliferation and differentiation, demonstrating that complex coatings are beneficial 
. However, there are many potential combinations, and using a natural matrix would be more physiologically relevant.
In this study, we have presented a method to create matrix coatings derived from porcine adult tissues, performed analysis to determine the components of the solubilized extracellular matrix, and then ensured that the surface composition retained its complexity after adsorption onto tissue culture plastic. We hypothesized that these coatings would have a beneficial effect within 2D muscle culture systems as they more appropriately emulate the native muscle ECM in vitro
. This culture substrate would thus allow for desirable cell-matrix interactions and provide a better platform for cell phenotype and differentiation, similar to that found in vivo
. A potential limitation, however, of this approach is that these matrices are of porcine origin, which has the potential for disease transmission and immune recognition. However, the FDA has approved many decellularized xenogeneic ECMs for implantation including porcine dermis, small-intestine submucosa, and heart valves 
and therefore, we anticipate that these matrices will be a viable option for cell culture. For clinical translation of any cells grown on these coatings, appropriate quality control and testing will of course be essential to ensure lack of pathogens.
The goal of this study was to demonstrate that the simple method for fabricating naturally derived, tissue specific matrix coatings could provide a cell culture substrate that emulates the native ECM microenvironment, is readily available, and is as simple to use as conventional protein coatings. The ECM plays an important role in directing progenitor and stem cell differentiation and maturation 
and we thus examined the potential for these tissue specific coatings in committed progenitor and stem cell culture. Differentiation of muscle progenitor cells was studied using C2C12 skeletal myoblasts on adult skeletal muscle matrix and compared to a conventional collagen coating I 
. To examine the potential of the adult myocardial matrix as a coating, we examined its effect on the morphology and maturation of hESC derived cardiomyocytes as compared to the standard gelatin coating typically used in stem cell derived cardiomyocyte cultures 
since we hypothesized that the adult cardiac matrix coating could further promote maturation of these cells.
Our data shows that the native tissue matrix enhanced differentiation of C2C12 skeletal myoblasts and maturation of human embryonic stem cell derived cardiomyocytes when compared to conventional cell culture coatings. While these extracellular matrix coatings contains many biochemical cues of the native environment, one limitation of this study is that it is likely that some ECM components have been lost during processing. However, the remaining matrix components do affect cell differentiation and maturation. S
keletal muscle matrix contains native cues that allowed for increased differentiation and larger myotubes to develop from skeletal myoblasts when compared to a standard single protein coating. In addition, the cardiac matrix enhanced the formation and organization of multicellular clusters with intercellular desmosomal like structures resembling the cardiac intercalated disc within hESC derived cardiomyocytes. Thus, this report highlights that the cell microenvironment and subtle differences in matrix composition can play an important role on cell phenotype in vitro
. We show a method that can allow one to more closely recapitulate this microenvironment in 2D cell culture, which could be applied to any type of cell culture assay. Given that the origin of these matrices is adult ECM, it is likely more applicable to terminal differentiation/maturation and adult cell culture. There is also a potential application for cell culture using other cell types, as to date, we have created coatings from liver, brain, and other muscle tissue and therefore anticipate that this process can be used to generate substrate coatings from any non-mineralized tissue to present the appropriate cell-matrix interactions. 3D culture systems have recently been highlighted as a better mimic of the in vivo
, and similar matrix solutions to those employed here as coatings can self assemble into thin films or gels for 3D cell culture 
. The 3D environment is not, however, always suitable for all culture studies. Herein, we have developed a simple method to produce large amounts of coating material that would provide a better approximation of the in vivo
microenvironment with the added benefit of tissue specificity and complexity. The results of this study show the potential of decellularized, solubilized extracellular matrix coatings derived from muscle to promote maturation of committed progenitor and stem cells in vitro
, demonstrating this method's applicability to muscle cell culture; however, the general technology has wide ranging implications.