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Tissue engineering
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===Scaffolding=== In 2013, using a 3-D scaffolding of [[Matrigel]] in various configurations, substantial pancreatic [[organoid]]s was produced in vitro. Clusters of small numbers of cells proliferated into 40,000 cells within one week. The clusters transform into cells that make either digestive [[enzyme]]s or [[hormone]]s like [[insulin]], self-organizing into branched pancreatic organoids that resemble the pancreas.<ref name="Greggio_2013">{{cite journal |vauthors=Greggio C, De Franceschi F, Figueiredo-Larsen M, Gobaa S, Ranga A, Semb H, Lutolf M, Grapin-Botton A |display-authors=6 |title=Artificial three-dimensional niches deconstruct pancreas development in vitro |journal=Development |volume=140 |issue=21 |pages=4452β4462 |date=November 2013 |pmid=24130330 |pmc=4007719 |doi=10.1242/dev.096628 |doi-access=free}}<br />Lay summary: {{cite web |url=http://www.kurzweilai.net/new-3d-method-used-to-grow-miniature-pancreas-model |date=October 17, 2013 |title=New 3D method used to grow miniature pancreas model |website=Kurzweil }}</ref> The cells are sensitive to the environment, such as gel stiffness and contact with other cells. Individual cells do not thrive; a minimum of four proximate cells was required for subsequent organoid development. Modifications to the medium composition produced either hollow spheres mainly composed of pancreatic progenitors, or complex organoids that spontaneously undergo pancreatic morphogenesis and differentiation. Maintenance and expansion of pancreatic progenitors require active [[Notch signaling|Notch]] and [[Fibroblast growth factor|FGF]] signaling, recapitulating in vivo niche signaling interactions.<ref name="Greggio_2013"/> The organoids were seen as potentially offering mini-organs for drug testing and for spare insulin-producing cells.<ref name="Greggio_2013"/> Aside from Matrigel 3-D scaffolds, other collagen gel systems have been developed. Collagen/hyaluronic acid scaffolds have been used for modeling the mammary gland In Vitro while co-coculturing epithelial and adipocyte cells. The HyStem kit is another 3-D platform containing ECM components and hyaluronic acid that has been used for cancer research. Additionally, hydrogel constituents can be chemically modified to assist in crosslinking and enhance their mechanical properties.{{cn|date=April 2025}}
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