ABSTRACT
Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.
ABSTRACT
With the advancements in tissue engineering and three-dimensional (3D) bioprinting, physiologically relevant three-dimensional structures with suitable mechanical and bioactive properties that mimic the biological tissue can be designed and fabricated. However, the available bioinks are less than demanded. In this research, the readily available biomass sources, keratin and glycol chitosan, were selected to develop a UV-curable hydrogel that is feasible for the 3D bioprinting process. Keratin methacrylate and glycol chitosan methacrylate were synthesized, and a hybrid bioink was created by combining this protein-polysaccharide cross-linked hydrogel. While human hair keratin could provide biological functions, the other composition, glycol chitosan, could further enhance the mechanical strength of the construct. The mechanical properties, degradation profile, swelling behavior, cell viability, and proliferation were investigated with various ratios of keratin methacrylate to glycol chitosan methacrylate. The composition of 2% (w/v) keratin methacrylate and 2% (w/v) chitosan methacrylate showed a significantly higher cell number and swelling percentage than other compositions and was designated as the bioink for 3D printing afterward. The feasibility of stem cell loading in the selected formula was examined with an extrusion-based bioprinter. The cells and spheroids can be successfully printed with the synthesized bioink into a specific shape and cultured. This work provides a potential option for bioinks and delivers insights into personalization research on stem cell-laden biofabricated hydrogels in the future.
