Abstract
The covalent functionalization of type I atelocollagen with either 4-vinylbenzyl or methacrylamide residues is presented as a simple synthetic strategy to achieve customizable, cell-friendly UV-cured hydrogel networks with widespread clinical applicability. Molecular parameters, i.e., the type of monomer, degree of atelocollagen functionalization and UV-curing solution, have been systematically varied and their effect on gelation kinetics, swelling behavior, elastic properties, and enzymatic degradability investigated. UV-cured hydrogel networks deriving from atelocollagen precursors functionalized with equivalent molar content of 4-vinylbenzyl (F4VBC = 18 ± 1 mol.%) and methacrylamide (FMA = 19 ± 2 mol.%) adducts proved to display remarkably-different swelling ratio (SR = 1963 ± 58–5202 ± 401 wt.%), storage modulus (G′ = 17 ± 3–390 ± 99 Pa) and collagenase resistance (μrel = 18 ± 5–56 ± 5 wt.%), similarly to the case of UV-cured hydrogel networks obtained with the same type of methacrylamide adduct, but varied degree of functionalization (FMA = 19 ± 2 – 88 ± 1 mol.%). UV-induced network formation of 4VBC-functionalized atelocollagen molecules yielded hydrogels with increased stiffness and enzymatic stability, attributed to the molecular rigidity of resulting aromatized crosslinking segment, whilst no toxic response was observed with osteosarcoma G292 cells. Although to a lesser extent, the pH of the UV-curing solution also proved to affect macroscopic hydrogel properties, likely due to the altered organization of atelocollagen molecules during network formation. By leveraging the knowledge gained with classic synthetic networks, this study highlights how the type of monomer can be conveniently exploited to realize customizable atelocollagen hydrogels for personalized medicine, whereby the structure-property relationships can be controlled to meet the requirements of unmet clinical applications.
Highlights
As a simple mimetic of the extracellular matrix (ECM) of biological tissues hydrogels have been widely applied in the biomedical field (Zhang and Khademhosseini, 2017), for applications including regenerative medicine (Heller et al, 2013), wound care (Konieczynska et al, 2016), and controlled drug delivery (Chen et al, 2017)
The solution-induced effect observed in AC products functionalized with equivalent molar content of methacrylamide and 4-vinylbenzyl residues is in agreement with the results reported by Ratanavaraporn et al (2008), whereby increased solution viscosity and hydrogel compressive modulus were measured when native type I collagen was dissolved in aqueous solutions of decreased acidity
The introduction of either 4-vinylbenzyl or methacrylamide adducts onto type I atelocollagen proved successful to enable the synthesis of customizable UV-cured hydrogel networks, depending on the type of monomer, degree of atelocollagen functionalization, and UV-curing solution
Summary
As a simple mimetic of the extracellular matrix (ECM) of biological tissues hydrogels have been widely applied in the biomedical field (Zhang and Khademhosseini, 2017), for applications including regenerative medicine (Heller et al, 2013), wound care (Konieczynska et al, 2016), and controlled drug delivery (Chen et al, 2017). Other than linear biopolymers, such a level of customization is still hardly realized when employing biopolymers with increased organizational complexity, such as collagen, because of the inherently-limited chemical accessibility and solubility Customization of these building blocks would on the other hand enable the formation of systems with superior biofunctionality and widespread clinical applicability. The use of toxic reagents and the relatively-long reaction time prevent the application of these synthetic strategies for the delivery of cell-friendly, in-situ forming hydrogels (Lee et al, 2013) or to achieve material customization at the bed side Another challenge associated with above-mentioned strategies is that the enzymatic degradability of resulting collagen materials is still relatively quick, so that the requirements of specific clinical application, e.g., in guided bone regeneration, cannot be entirely fulfilled (Calciolari et al, 2018). Above-mentioned crosslinking strategies are often associated with unwanted side reactions, so that defined structure-property relationships are hardly-developed (Yunoki and Matsuda, 2008; Tronci et al, 2010; Duan et al, 2014)
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