168 Chapter 7 Hydrogels from Synthetic vs Natural materials When considering the possibilities for generating 3D microenvironments in which lung cells can prosper there are many different options available. Within the tissue engineering field much work has concentrated on the development of polymers from which soft or stiff hydrogels can be cast or 3D printed [18-21]. These synthetic polymers (including poly acrylamide [22] and dextran [23]) offer many opportunities for tuning biomechanical and structural properties of the microenvironment but are generally inhospitable environments for cells, requiring the addition of cell binding epitopes, such as RGD motifs, to enable cellular attachment [24-26]. Alternatively, natural ECM components have also been used to generate single component hydrogels that readily support cell attachment, but are more limited in the possibilities for tuning their biomechanical properties. Examples of such hydrogels include collagen type I, fibrin, gelatin (methacrylate)and hyaluronan [27-34]. Such hydrogels provide the 3D environment for cells, modelling the dimensionality and possibly the biomechanical mimicry of the in vivo situation, but they are not reflective of the complexity of the ECM components within the tissue microenvironment. Hydrogels developed from the solubilized basement membrane matrix secreted by Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells (marketed as Matrigel or Geltrex) have been used for more than 35 years to support cell growth for specific assays, particularly focussing on stem cell expansion assays [35-38]. However, not all cells thrive in such an environment and there are limited possibilities to manipulate the composition and biomechanical environment herein. A recent advance for the lung field has been the development of hydrogels generated from ECM derived from decellularized lungs. Porcine lung ECM-derived hydrogels were initially reported [39], while human lung ECM-derived hydrogels have recently been established [2]. This perspective article presents the latest advances in lung ECM-derived hydrogels with respect to their development, modification, characterization and utilization. Moreover, it explores opportunities and challenges for the field, highlighting where future research should focus to improve the comparability of data generated with different measurement systems using lung ECM-derived hydrogels. Finally, we discuss the multi-disciplinary nature of the research required to move these model systems forward.
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