Characteristics of Collagen-Rich Extracellular Matrix Hydrogels and Their Functionalization with Poly(ethylene glycol) Derivatives for Enhanced Biomedical Applications: A Review

Abstract

The hydrogels of natural extracellular matrix (ECM) are excellent biomaterials with promising applications in the physiological manufacture of three-dimensional (3D) constructs that replicate native tissue-like architectures and function as cargo-delivery, 3D bioprinting, or injectable systems. ECM hydrogels retain the bioactivity to trigger key cellular processes in the tissue engineering and regenerative medicine (TERM) strategies. However, they lack suitable physicochemical properties, which restricts their applications in vivo. This demand that mechanical and degradation properties of the ECM hydrogels must be balanced against biological properties. By incorporating poly­(ethylene glycol) (PEG) into mammalian type I collagen-rich ECM substrates, this task can be accomplished. This review is focused on the use of PEG derivatives, widely used in formulations of pharmaceutical products or in synthesis of biomedical polyurethanes, as a strategy to modulate both physical and biological properties of natural ECM hydrogels. The processing–property relationship in decellularized ECM hydrogels, as well as the main results when used in TERM, are discussed. A comparison of the characteristics of PEG-ECM hydrogels is provided in terms of the improvement of structure, mechanics, and degradation behavior. Finally, the benefits of producing PEG-ECM hydrogels according to in vitro and in vivo performance in different proofs-of-concept of emergent biomedical technologies are overviewed.

Novel semi‐interpenetrated networks based on collagen‐polyurethane‐polysaccharides in hydrogel state for biomedical applications

“…It has been reported that the polymerization of collagen to form fibers depends on the concentration of PU, and that concentrations in weight higher than 60% prevent the process of collagen fibrilogenesis 21 . Other systems of semi‐IPN collagen hydrogels with PVA, 8 PEG, 9 chitosan 15,16 and cellulose 19 reveal that concentrations less than 10 wt% of the components do not alter the capacity of collagen fiber formation, generating fibrillary semi‐interpenetrated systems with these chemical agents.…”

“…For it, several chemical cross-linkers that have been used: genipin, glutaraldehyde, carbodiimide, PEG derivatized with reactive groups, among others. 3,9,11,12 Recently, a novel method for the preparation of crosslinked collagen hydrogels with trifunctional polyurethane prepolymers (PPU) has been reported. 13 The urea cross-linking bonds produced by the condensation reaction of the primary amino groups of the collagen with the isocyanate ends of PPU produce hybrid 3D matrices with tailored mechanical properties, improved swelling capacity and regulated proteolytic degradation rate, despite that, this system does not present antibacterial capacity and limits cell viability to high concentrations of PPU by cytotoxic effects.…”

“…These hybrid matrices are formed by entangling interactions promoted by hydrogen bonds among the components, these systems are commonly known as semi‐interpenetrated networks (semi‐IPN) hydrogels. Among these biomaterials, semi‐IPN collagen hydrogels with polyvinyl alcohol (PVA), 8 polyethyleneglycol (PEG), 9 2‐methacryloyloxyethyl phosphorylcholine, 10 among others have been reported.…”

“…On the other hand, the formation of novel semi‐IPN hydrogels requires that the collagen be chemically cross‐linked in order to allow mechanical coupling among the semi‐IPN phases. For it, several chemical cross‐linkers that have been used: genipin, glutaraldehyde, carbodiimide, PEG derivatized with reactive groups, among others 3,9,11,12 …”

High-Strength Albumin Hydrogels With Hybrid Cross-Linking

“…However, the poor mechanical properties of natural protein hydrogels is one of the main drawbacks impeding their application in some cases (Silva et al, 2017;Tang et al, 2018). Recently, great efforts have been made to enhance the mechanical properties of natural protein hydrogels, and some strategies have been developed, including nanocomposite (Yuk et al, 2016;Qin et al, 2017;Wang et al, 2017Wang et al, , 2018, physical cross-linking (Toivonen et al, 2015;Feng et al, 2018;Yan et al, 2019;Zhang et al, 2019), solvent induction (Li et al, 2016;Zhang et al, 2016;Hashemnejad et al, 2017;Zhu et al, 2018), double network (Bhattacharjee et al, 2015;Luo et al, 2016;Rangel-Argote et al, 2018;Tavsanli and Okay, 2019), hybrid cross-linking (Moura et al, 2011;Epstein-Barash et al, 2012;Xu et al, 2016;Nojima and Iyoda, 2018;Yang et al, 2018), and so on.…”