Abstract
Hydrogels based on photocrosslinkable Hyaluronic Acid Methacrylate (HAMA) and Chondroitin Sulfate Methacrylate (CSMA) are presently under investigation for tissue engineering applications. HAMA and CSMA gels offer tunable characteristics such as tailorable mechanical properties, swelling characteristics, and enzymatic degradability. This review gives an overview of the scientific literature published regarding the pre-clinical development of covalently crosslinked hydrogels that (partially) are based on HAMA and/or CSMA. Throughout the review, recommendations for the next steps in clinical translation of hydrogels based on HAMA or CSMA are made and potential pitfalls are defined. Specifically, a myriad of different synthetic routes to obtain polymerizable hyaluronic acid and chondroitin sulfate derivatives are described. The effects of important parameters such as degree of (meth)acrylation and molecular weight of the synthesized polymers on the formed hydrogels are discussed and useful analytical techniques for their characterization are summarized. Furthermore, the characteristics of the formed hydrogels including their enzymatic degradability are discussed. Finally, a summary of several recent applications of these hydrogels in applied fields such as cartilage and cardiac regeneration and advanced tissue modelling is presented.
| Original language | English |
|---|---|
| Article number | 120602 |
| Pages (from-to) | 1-24 |
| Number of pages | 24 |
| Journal | Biomaterials |
| Volume | 268 |
| DOIs | |
| Publication status | Published - 1 Jan 2021 |
Bibliographical note
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.Funding
Collagen is another biopolymer that has been blended with HAMA to fabricate hybrid hydrogels for biomedical applications. Sewell-Loftin et al. blended collagen type I within a HAMA hydrogel matrix. Collagen type I was mixed with HAMA stock solution prior to UV-crosslinking. The resulting semi-IPN (one component of the network is crosslinked, the other is only entangled) was used to study mechanical cues affecting epithelial to mesenchymal transition (EMT) of endocardial cells, which are essential for heart valve formation [216]. Controllable stiffness and mechanical properties of the hybrid hydrogel allowed for studying of the EMT phenomenon in vitro. The authors demonstrated that mechanical forces indeed play an important role in endocardial EMT and that the prepared hydrogel represents a good platform for studying valve disorders and can act as starting point for developing tissue engineered heart valves. Brigham et al. prepared a semi-IPN from HAMA and collagen type I [144]. The polymers were mixed at the desired concentration in cell culture medium and subsequently exposed to UV, resulting in photocrosslinking of HAMA. The mechanical properties, and in particular compressive moduli, of the HAMA/collagen hydrogels increased as a function of DM of HAMA. Moreover, these gels displayed better fibroblasts viability in comparison to HAMA hydrogel. To explain, fibroblasts adhered to the hybrid hydrogels and proliferated more than on the HAMA gels alone, whereas upon encapsulation, cells maintained high viability. Because of the good mechanical properties and good cytocompatibility, HAMA/collagen semi-IPNs could be of great value in soft tissue engineering applications. A similar system was studied by Suri et al. where a solution of HAMA in PBS and collagen solution (diluted with 0.2% acetic acid) were mixed together and subsequently supplemented with a HEPES solution and DMEM medium. The resulting solution was incubated at 37 ?C and allowed to undergo fibrillogenesis process (assembly of collagen fibrils) for 90 min to yield a collagen network [138]. In the following step, the obtained collagen gel was exposed to UV, allowing photocrosslinking of HAMA and resulting in the formation of an IPN. When compared to the corresponding single-component gels, the HAMA/collagen gels exhibit superior mechanical properties and slower enzymatic degradation in vitro due to higher crosslink density. Additionally, collagen/HAMA IPNs supported human dermal fibroblast adhesion and proliferation, indicating the suitability of HAMA/collagen IPN for the development of tissue engineering constructs.This work was performed under the framework of Chemelot InSciTe, supported by the partners of Regenerative Medicine Crossing Borders (www.regmedxb.com) and powered by Health~Holland, Top Sector Life Sciences & Health. C.C.L.S. acknowledges a personal grant from the Future Medicines Program financed by the Netherlands Organisation for Scientific Research (NWO) under grant nr. 022.006.003. This work was performed under the framework of Chemelot InSciTe, supported by the partners of Regenerative Medicine Crossing Borders ( www.regmedxb.com ) and powered by Health~Holland , Top Sector Life Sciences & Health . C.C.L.S. acknowledges a personal grant from the Future Medicines Program financed by the Netherlands Organisation for Scientific Research ( NWO ) under grant nr. 022.006.003.
Keywords
- (meth)acrylation
- CSMA
- Enzymatic degradation
- HAMA
- In vitro tissue models
- Regenerative medicine