Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration

Abstract

The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-µm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE.

Decellularized Skin Extracellular Matrix (dsECM) Improves the Physical and Biological Properties of Fibrinogen Hydrogel for Skin Bioprinting Applications

“…The fibrinogen hydrogels typically used for bioprinting applications are commonly supplemented with gelatin and hyaluronic acid [22]. DsECM contains multiple ECM components, including collagen I and collagen III fragments, glycoproteins, and glycosaminoglycans [23]. The combination of fibrinogen hydrogel and dsECM in our study supports the structural integrity of the printed construct and provides normal skin ECM components.…”

Cells, Materials, and Fabrication Processes for Cardiac Tissue Engineering

“…Allergic and anti-inflammatory side reactions have been reported with some silk derivatives, so care should be taken when incorporating them into an engineered tissue. Amongst natural hydrogels, decellularised ECM (dECM) has attracted significant interest since the breakthrough discovery of the process, as applied to the building of tissues (Ott et al, 2008;Belviso et al, 2020). In principle, dECM retains all components of the ECM of origin, thus creating a more complex and biomimetic environment.…”

Progress in cardiovascular bioprinting

“…dECM scaffolds mimic tissue‐specific components in 3D printed tissue products 65,66 . The use of decellularized scaffolds for cardiac tissue engineering application has been progressed in the past decade 22,67,68 . Ott et al in 2008, reported the first acellular rat whole heart by coronary perfusion method using a detergent solution containing 1% sodium dodecyl sulfate (SDS) and 1% Triton X‐100 in deionized water.…”