Bioactive molecules for modification of PEG hydrogels Biomimetic scaffolds usually mimic one or more biofunctions of the natural ECM by incorporation of different types of ECM-derived bioactive molecules (BMs) in the materials. specific cell adhesion, proteolytic degradation, and signal molecule-binding. A number of cell types have been immobilized on bioactive PEG hydrogels to provide fundamental knowledge of cell/scaffold interactions. This review addresses the recent progress in material designs and fabrication approaches leading to the development of bioactive hydrogels as tissue engineering scaffolds. with spatial and temporal control and in a variety of 3D structures with encapsulation of cells and biological agents [27,28]. PEG acrylates are the major type of macromers used for photopolymerization, including PEG diacrylate (PEGDA), PEG dimethacrylate (PEGDMA), and multiarm PEG (n-PEG) acyrlate (n-PEG-Acr). PEG hydrogels are not naturally degradable, but can be altered to enhance degradation by incorporating degradable segments, such as polyester [29C31], poly(propylene fumarate) (PPF) [32,33], acetal [34] and disulfide [35]. A convenient selection of the hydrolytically degradable blocks is polyhydroxyacids, including poly(lactic acid) (PLA), and poly(glycolic acid) (PGA), and polycaprolactone (PCL). Triblock (ABA) polymers, PLA-PEG-PLA and PGA-PEG-PGA have been synthesized by ring opening polymerization, terminated with acrylates to generate PLA-PEG-PLA diacrylate and PGA-PEG-PGA diacrylate, respectively [29,36,37]. In addition, the thiol-acrylate reaction has been used to make hydrogels with enhanced degradation of the ester bonds linked to Clozapine PEG chains [38C43]. PEG hydrogels are attractive scaffolds to provide 3D templates in aqueous environments for tissue regeneration; however, PEG hydrogels typically exhibit minimal or no intrinsic biological activity due to the nonadhesive nature of PEG chains [13]. It is noted that anchorage-dependent cells encapsulated in PEG hydrogels show low viability due to the bio-inert characteristic of PEG [42,43]. Inspired by nature, researchers have developed a variety of bioactively modified PEG hydrogels to mimic the natural extracellular matrix (ECM) [44C47]. Human tissues are built of different types of cells embedded within dynamic ECM hydrogels, which are composed of various proteins and glycans (polysaccharides) secreted by the cells. ECM components play a crucial instructive role Rabbit Polyclonal to TUSC3 in mediating cell functions, and possess critical biological functions like cell adhesion, proteolytic degradation and growth factor binding [48,49]. Thus, the natural ECM is an attractive model for design and fabrication of bioactive scaffolds for tissue engineering [45C49]. To tether ECM-derived bioactive molecules (BMs) to PEG hydrogels, various strategies have been developed to provide fundamental knowledge to understand cell/scaffold interactions [44,45]. A number of cell lines have been explored to immobilize on bioactive PEG hydrogels, including fibroblasts, chondrocytes, vascular smooth muscle cells (SMCs) and endothelial cells (ECs), osteoblasts, neural cells, and stem cells [46,47]. Much effort has been devoted to the control of ligand density and spatial distribution in PEG hydrogels to modulate specific cellular responses for tissue formation [34,37,50,53]. This review addresses the recent progress in material designs and fabrication approaches that are leading to the development of bioactive PEG hydrogels as tissue engineering scaffolds. As the fundamental biology of the cellular microenvironment is often the inspiration for material design, this review begins with a brief discussion of the structure and biofunctions of the natural ECM model for biomimetic modification, and then highlights the ECM-derived biomolecules that have been used to make various bioactive PEG hydrogels, followed by summarizing the current approaches for preparation of bioactive PEG hydrogels with the control of specific cues, such as cell adhesion, proteolytic degradation and growth factor-binding. Finally, brief conclusions are provided regarding bioactive PEG hydrogels and challenges in Clozapine biomimetic scaffold modification. 2. ECM as a natural model for bioactive modification The rapid increase in the understanding of matrix biology has provided opportunities to use the natural ECM as a model for designing biomimetic scaffolds. This Clozapine section discusses the structure and biofunctions of the ECM and the general strategies for ECM-mimetic modification of PEG hydrogels. 2.1. ECM structure and components The tissues of the human body contain significant extracellular space, into which ECM molecules are secreted by the cells to form a complex network (Fig. 2) [55,56]. The ECM provides mechanical support for tissues, organizes cells into specific tissues, Clozapine and controls cell behavior. Generally, the natural ECM consists of two classes of biomacromolecules, proteins and glycans [55C57]. The Clozapine ECM proteins include structural fibrous proteins (e.g., collagen, elastin and fibrin) and cell adhesive proteins (e.g., fibrolectin and laminin). Collagen, the most abundant protein in mammals,.