TABLE 1.
Compiled effects of substrate stiffness and architecture on various pancreatic differentiation platforms.
| Author | Cell type | Differentiation type | Platform | ECM coating | Apparent modulus (kPa) | Cell morphology | Relative stiffness | Impact |
| Architecture | ||||||||
| Ghanian et al., 2015 | hESCs | Directed S0 → S1 | Electrospun poly(ε-caprolactone) | Matrigel | Not reported | Clumped | – | hESCs cultured on small diameter nanofibers adopted a clumped morphology and had improved definitive endoderm differentiation. |
| Tissue culture polystyrene (control) | Matrigel | 3 × 106* | Spread | Stiff | ||||
| Maldonado et al., 2017 | iPSCs | Directed S0 → S3 | Electrospun poly(ε-caprolactone) | Col I | 20 | Round, 3D colonies + | Soft | “Soft” nanofibers promoted posterior foregut and pancreatic differentiation. “Stiff” surfaces promoted mesodermal differentiation while downregulating pancreatic differentiation. |
| Electrospun polyether-ketone-ketone | Col I | 300 | Spread, flattened 2D colonies + | Stiff | ||||
| Tissue culture polystyrene (control) | Col I | 3 × 106* | Stiff | |||||
| Substrate stiffness | ||||||||
| Narayanan et al., 2013 | hESCs | Spontaneous differentiation | Hyaluronic acid hydrogels | Col IV, Fn, Lam | 1.3–3.5 | Not reported | Soft | Optimal differentiation with 2.1 kPa gels and a 1/3/3 mixture of Col IV, fibronectin, and laminin. |
| Tissue culture polystyrene (control) | RIN5F ECM | 3 × 106* | Not reported | |||||
| Rasmussen et al., 2016b | hESCs | Directed S0 → S3 | High aspect ratio polycarbonate nanopillars | Fn | 34.6 | Small, tight 2D clusters. Elongated and aligned with nanopillars | Soft | Poor hESC adhesion on soft nanopillars. “Soft” surfaces promoted endoderm (S1) differentiation. Control had significantly higher PDX1 protein expression (S3) compared to test conditions. |
| Low aspect ratio polycarbonate nanopillars | Fn | 2800 | Spread | Stiff | ||||
| Tissue culture polystyrene (control) | Fn | 3 × 106* | Spread | Stiff | ||||
| Richardson et al., 2016 | hESCs | Directed S0 → S3 | Low concentration barium alginate capsules | N/A | 3.9 ± 1.3 | Larger circular 3D colonies | Soft | “Soft” capsules increase hESC proliferation and were highly PDX1+ (S3). Localized deposition of Col I and Lam in “soft” capsules. “Stiff” capsules support endodermal (S1) differentiation but downregulates pancreatic differentiation. |
| High concentration barium alginate capsules | N/A | 73.2 ± 22.4 | Small, growth restricted 3D colonies and large, elongated 3D colonies | Stiff | ||||
| Kim et al., 2019 | Rat islets and PSCs | Directed S0 → S7 | dECM bio-ink | Human pdECM | 3 | Not reported | - | Insulin secretion and maturation were enhanced in cells cultured in pdECM bioinks compared to 2D tissue culture polystyrene (TCPS), alginate gels, and collagen gels |
| Collagen gel | Col I | 100 | Not reported | – | ||||
| Tissue culture polystyrene (control) | – | 3 × 106* | – | |||||
| Hogrebe et al., 2020 | PSCs | Directed S0 → S7 | Tall collagen I gel | Col I | N/A | Not reported | Soft | Decreased stiffness via increasing gel height promotes overall endocrine induction (increases NGN3, NKX2.2, NEUROD1 and decreases SOX9, NKX6.1 expression) |
| Short collagen I gel | Col I | N/A | Not reported | Stiff | ||||
| Pennarossa et al., 2018 | Mouse dermal fibroblasts | Transdifferentiation | Polyacrylamide hydrogels | Col I | 0.1 | 2D epithelioid structure in small, scattered clusters | Soft | Improved transdifferentiation toward monohormonal pancreatic endocrine cells on soft substrates |
| Tissue culture polystyrene (control) | Col I | 3 × 106* | 3D spherical structures | Stiff | ||||
Fn, fibronectin; Lam, laminin; Col, collagen; pdECM, pancreatic decellularized extracellular matrix. *Stiffness of polystyrene shown for reference taken from Gilbert et al. (2010). +Cell morphology details taken from previous work from same group (Maldonado, 2015).