Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids

Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases

“…This study further charted the mechanical requirement for organoid growth and demonstrated that stiff ECM is essential for the initial expansion phase of intestinal stem cells, whereas ECM softening by proteolysis promotes subsequent organoid formation and differentiation. Another study found that the incorporation of the α2β1 integrin affinity motif found in type I collagen allows for enhanced recovery and expansion of human intestinal and endometrial organoids 147 . These are good examples of how fractionalizing the dependency of organoids on BMM and ECM properties can navigate the synthesis of minimal and defined hydrogels for organoid culture.…”

Physiomimetic Models of Adenomyosis

“…120 These models employing natural ECMs have shortcomings, in part because there are no "one-size-fits-all" ECMs for both epithelia and stroma (and potentially other cell types), and also because natural proteins are impure (Matrigel has myriad growth factors); are substantially variable from lot-to-lot; are relatively rapidly degraded by cells; and are subject to variation in structural and mechanical properties depending on how quickly or slowly the gels are polymerized. 115,121 Variation is further exacerbated as some investigators use atelocollagen, which yields very different outcomes than whole collagen. 122 These shortcomings have prompted a sustained effort in the biomaterials community to create synthetic alternatives to Matrigel and collagen.…”

“…123,124 A popular approach exploits the relative inertness of poly(ethylene glycol) (PEG), which is commercially available in multi-arm star/branched configurations activated with cell-compatible reactive groups, to create modular cell-encapsulating hydrogels crosslinked with short matrix metalloprotease (MMP)-sensitive peptides and incorporating synthetic integrin-binding motifs. 121,[123][124][125][126] Other types of synthetic gel ECMs based entirely on synthetic proteins or semisynthetic gels based on modified hyaluronic acid are also widely used. 124,127 The local and bulk mechanical modulus, permeability, degradation properties, and biochemical recognition motifs-all of which have been correlated to cell responses 115,121,125 -can be tuned independently to match the needs of individual cells and tissues.…”

“…121,[123][124][125][126] Other types of synthetic gel ECMs based entirely on synthetic proteins or semisynthetic gels based on modified hyaluronic acid are also widely used. 124,127 The local and bulk mechanical modulus, permeability, degradation properties, and biochemical recognition motifs-all of which have been correlated to cell responses 115,121,125 -can be tuned independently to match the needs of individual cells and tissues.…”

A bioengineering perspective on modelling the intestinal epithelial physiology in vitro

“…With the relationship in biological tissues being E = 3G 68 , this would correspond to G = 967 Pa, indeed in the range observed to be optimal for culturing intestinal epithelial organoids. Interestingly, a subsequent study found that a PEG-based matrix functionalised with the cell adhesion domains from type I collagen (GFOGER) on its own was sufficient as a matrix in supporting the growth of primary human intestinal epithelial cells as spheroids 69 . This again points to the important role of biomechanical cues in controlling cell fate and is supported by the observation that organoid 'crypt' formation depends on local mechanical signals as the length and the number of crypts per organoid can be modulated by softening the matrix 70 .…”