Extracellular Matrix Origin Directs Morphogenesis and Gene Regulation in Bioengineered Human Skin

科学分野:

• Tissue Engineering
• Regenerative Medicine
• Biomaterials Science

背景:

• The cellular microenvironment, particularly the extracellular matrix (ECM), provides critical biochemical and mechanical cues for tissue development, repair, and homeostasis.
• The ECM instructs cell fate and function by guiding transcriptional programs.
• Understanding the impact of ECM origin is vital for successful biofabrication of functional tissues.

研究 の 目的:

• To investigate the influence of endogenous versus exogenous extracellular matrix (ECM) on the biofabrication of human skin equivalents.
• To compare the transcriptional profiles and structural characteristics of skin constructs utilizing different ECM sources.
• To assess the suitability of various scaffolds for creating physiologically relevant skin tissue in vitro.

主な方法:

• Biofabrication of human skin equivalents using fibroblast-assembled endogenous ECM and exogenous collagen-based scaffolds.
• Comparative analysis of full-thickness skin models.
• RNA sequencing to evaluate transcriptional trajectories.
• Histological assessment of tissue architecture, including the dermal-epidermal junction (DEJ).

主要な成果:

• ECM origin significantly impacts transcriptional profiles and morphogenetic processes in skin equivalents.
• Skin equivalents with endogenously produced ECM exhibited physiologically relevant architecture and a well-organized DEJ.
• Constructs based on exogenous matrices showed abnormal epithelial expansion and failed to replicate key structural features.

結論:

• Recapitulating the native extracellular matrix (ECM) is essential for generating functional human skin equivalents in vitro.
• The choice of scaffold material profoundly influences the development and structural integrity of engineered tissues.
• These findings have critical implications for scaffold selection in regenerative medicine and tissue engineering applications.