Engineering the extracellular matrix for clinical applications: Endoderm, mesoderm, and ectoderm

Abstract

Tissue engineering is rapidly progressing from a research-based discipline to clinical applications. Emerging technologies could be utilized to develop therapeutics for a wide range of diseases, but many are contingent on a cell scaffold that can produce proper tissue ultrastructure. The extracellular matrix, which a cell scaffold simulates, is not merely a foundation for tissue growth but a dynamic participant in cellular crosstalk and organ homeostasis. Cells change their growth rates, recruitment, and differentiation in response to the composition, modulus, and patterning of the substrate on which they reside. Cell scaffolds can regulate these factors through precision design, functionalization, and application. The ideal therapy would utilize highly specialized cell scaffolds to best mimic the tissue of interest. This paper discusses advantages and challenges of optimized cell scaffold design in the endoderm, mesoderm, and ectoderm for clinical applications in tracheal transplant, cardiac regeneration, and skin grafts, respectively.

Accelerated skin wound healing using electrospun nanofibrous mats blended with mussel adhesive protein and polycaprolactone

“…In particular, bFGF is a multifunctional growth factor that promotes the growth and differentiation of a broad spectrum of cell types, including dermal fibroblasts, keratinocytes, endothelial cells, and melanocytes, for wound healing . In the proliferative phase of the wound‐healing process, various types of growth factors and cytokines, including bFGF, are secreted for the active promotion of multiple steps, such as angiogenesis, granular tissue formation, and re‐epithelialization . Additionally, these growth factors play significant roles in the enhancement of the growth and differentiation of a broad spectrum of cell types participating in the wound‐healing process .…”

“…36 In the proliferative phase of the woundhealing process, various types of growth factors and cytokines, including bFGF, are secreted for the active promotion of multiple steps, such as angiogenesis, granular tissue formation, and re-epithelialization. 37 Additionally, these growth factors play significant roles in the enhancement of the growth and differentiation of a broad spectrum of cell types participating in the wound-healing process. 37 From the perspective that growth factors are readily enzymatically digested or deactivated and normally bind to ECM molecules to activate and stabilize target cells, the immobilization of growth factors has been considered an important issue for proper skin regeneration.…”

“…37 Additionally, these growth factors play significant roles in the enhancement of the growth and differentiation of a broad spectrum of cell types participating in the wound-healing process. 37 From the perspective that growth factors are readily enzymatically digested or deactivated and normally bind to ECM molecules to activate and stabilize target cells, the immobilization of growth factors has been considered an important issue for proper skin regeneration. 38 Therefore, the substantial ability of the MAP-blended nanofibers to capture growth factors, which could also retain secreted growth factors around the nanofibrous mats, might be one explanation for the enhanced skin regeneration observed in wounds of the PCL/MAP nanofibrous mat-treated group.…”

Challenging Regeneration to Transform Medicine

“…Therefore, such transplantable tissue must be rapidly constructed, while accurately emulating the function and structure of these complex organs and tissues. Rapid generation of functional tissues for transplantation will require expertise in diverse disciplines, including cell and developmental biology, immunology, tissue engineering, cell manufacturing, robotics, and imaging [5, 6]. Coordination of strategies to meet these challenges will more rapidly lead to breakthroughs in both regenerative medicine and our basic knowledge of human biology.…”

“…Alternatively, as an example of a bottom-up approach, cell layers or sheets can be individually grown and, if needed, stacked into more complex structures including sheet and tubular organs and tissues such as cornea, esophagus, vagina, and skin [5]. Another bottom-up approach is to use robotic systems to repeatedly print or place individual cells or groups of cells in prespecified three-dimensional positions within a binding matrix to form tissue and organ structures [9].…”