A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors - Neural Growth and Osteogenesis

[EN] Laminins (LMs) are important structural proteins of the extracellular matrix (ECM). The abundance of every LM isoform is tissue-dependent, suggesting that LM has tissue-specific roles. LM binds growth factors (GFs), which are powerful cytokines widely used in tissue engineering due to their ability to control stem cell differentiation. Currently, the most commonly used ECM mimetic material in vitro is Matrigel, a matrix of undefined composition containing LM and various GFs, but subjected to batch variability and lacking control of physicochemical properties. Inspired by Matrigel, a new and completely defined hydrogel platform based on hybrid LM-poly(ethylene glycol) (PEG) hydrogels with controllable stiffness (1-25 kPa) and degradability is proposed. Different LM isoforms are used to bind and efficiently display GFs (here, bone morphogenetic protein (BMP-2) and beta-nerve growth factor (beta-NGF)), enabling their solid-phase presentation at ultralow doses to specifically target a range of tissues. The potential of this platform to trigger stem cell differentiation toward osteogenic lineages and stimulate neural cells growth in 3D, is demonstrated. These hydrogels enable 3D, synthetic, defined composition, and reproducible cell culture microenvironments reflecting the complexity of the native ECM, where GFs in combination with LM isoforms yield the full diversity of cellular processesThe authors would like to thank Dr. Susan Lindsay and Prof. Sue Barnett for providing the rat pups for the extraction of DRGs. Kind thanks to Dr. Manlio Tassieri for allowing use of the Rheometer and his support in analysis and interpreting the data. All the OPN and OCN images rendering in 3D and data analysis was possible with the help of Mr. Colin Loney by allowing access to the Imaris software. The authors acknowledge support via an EPSRC Programme Grant (EP/P001114/1Dobre, O.; Oliva, MAG.; Ciccone, G.; Trujillo-Muñoz, S.; Rodrigo Navarro, A.; Venters, DC.; Llopis Hernández, V.... (2021). A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors - Neural Growth and Osteogenesis. Advanced Functional Materials. 31(21):1-15. https://doi.org/10.1002/adfm.202010225115312