Abstract
The tissue microenvironment has profound effects on tissue-specific regeneration. The 3-dimensional extracellular matrix (ECM) niche influences the linage-specific differentiation of stem cells in tissue. To understand how ECM guides tissue-specific regeneration, we established a series of 3D composite scaffolds containing ECMs derived from different primary cells isolated from a single animal species and assessed their impact on the differentiation of human mesenchymal stem cells (hMSCs). Synthetic microfiber scaffolds (fiber mats) were fabricated by electrospinning tyrosine-derived polycarbonates (pDTEC). The bovine primary fibroblasts, chondrocytes and osteoblasts cultured on the fiber mats produced and assembled their ECMs, infiltrating the pores of the fibrous scaffold. The composite scaffolds were decellularized to remove cellular components, preserve ECM and minimally affect polymer integrity. Characterization of the ECMs derived from different primary cells in the composite scaffolds showed overlapping but distinct compositions. The chondrogenic and osteogenic differentiation of hMSCs on the different composite scaffolds were compared. Our results showed that ECM derived from chondrocytes cultured in synthetic fiber mats promoted the chondrogenic differentiation of hMSC in the presence or absence of soluble inducing factors. ECM derived from co-culture of osteoblasts and chondrocytes promoted osteogenic differentiation in hMSCs better than ECM derived from chondrocytes. This study demonstrated that decellularized ECMs derived from different cell types formed within synthetic fiber scaffolds guide the tissue-specific differentiation of hMSCs. These composite scaffolds may be developed into models to study the mechanisms of ECM-induced tissue regeneration.Graphical
Highlights
Scaffolds are often required to support tissue repair, regeneration, or reconstruction following the loss of tissue caused by injury or disease [1]
Our results showed that extracellular matrix (ECM) derived from chondrocytes cultured in synthetic fiber mats promoted the chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in the presence or absence of soluble inducing factors
ECM derived from co-culture of osteoblasts and chondrocytes promoted osteogenic differentiation in hMSCs better than ECM derived from chondrocytes
Summary
Scaffolds are often required to support tissue repair, regeneration, or reconstruction following the loss of tissue caused by injury or disease [1]. Biological scaffolds are either generated through decellularization of tissue/organs or fabricated from purified extracellular matrix (ECM) components 100 Page 2 of 8. The disadvantage of decellularized tissue scaffolds is the limitation on donor tissue availability, sample uniformity, and compromised mechanical properties following decellularization [5]. Synthetic scaffolds can be designed and tailored to match the structure and mechanical properties of native tissue matrices, which makes them very promising candidates for tissue engineering [6, 7]. The lack of the biological activity in synthetic scaffolds remains a challenge for inducing tissue-specific regeneration. The recent development of composite scaffolds, which incorporates the ECM components or decellularized ECM matrix into synthetic scaffolds, often shows improved biological activity [8,9,10]
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