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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
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Extracellular Matrix Origin Directs Morphogenesis and Gene Regulation in Bioengineered Human Skin.

Francesco Galardo1,2,3, Giorgia Imparato1, Costantino Casale1,3

  • 1Istituto Italiano Di Tecnologia-IIT, Center for Advanced Biomaterials For Healthcare, Napoli, Italy.

Advanced Healthcare Materials
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PubMed
Summary
This summary is machine-generated.

Biofabricating functional human skin requires a native-like microenvironment. Endogenous extracellular matrix (ECM) supports proper gene expression and tissue architecture, unlike exogenous scaffolds, crucial for regenerative medicine.

Keywords:
ECMRNA‐Seq, transcriptomicsfull‐thickness skin equivalentgene expression profilingorganotypic culture

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Area of Science:

  • Tissue Engineering
  • Regenerative Medicine
  • Biomaterials Science

Background:

  • 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.

Purpose of the Study:

  • 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.

Main Methods:

  • 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).

Main Results:

  • 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.

Conclusions:

  • 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.