Multifunctional Natural-based Biomaterials Strategies for Cutaneous Tissue Engineering: Conventional Approach Towards Advance Technology ۳D-Bioprinting

Background: The irregular deep chronic wound is a grand challenge to be healed due to multiple factors, including slow angiogenesis that causes regenerated tissue failure. It presented an epidemic in millions of patients and resulted in amputations. The narrow gap of deep wounds could hinder and slow down normal wound healing. In order to overcome this, immediate treatment is a realistic strategy to minimize the risk of complications and aid in the healing rate of the cutaneous wound. Functionalized engineered biomaterials are proven to be a potential approach to embarking on skin wound management.Methods: In this research, several injectable formulations have been developed to explore further, starting from selecting fundamental biomaterials and combinations with various potential active compounds. The base technology used in these studies depends on the thermoresponsive approach. In addition, the injectable hydrogel formulations were printed using three-dimensional (۳D) bioprinting technology via the extrusion method. All hydrogel-base formulations were tested for their physico-chemical, cell-biomaterial interactions and efficiency in preclinical models.Results: The physicochemical and biocompatibility of all injectable hydrogels were respectively evaluated. They displayed the highest injectability degraded over two weeks with optimum swelling capacity and higher mechanical strength. Furthermore, the hydrogels offered higher porosity and lower wettability than the control. Surface and cross-section SEM photographs displayed an interconnected porous structure for tested groups. The chemical analysis represented no significant changes after GNP modification. Moreover, no toxicity effect of fabricated hydrogels against dermal fibroblasts was shown during the biocompatibility test. The hydrogels provided an excellent interconnected channel for cells migrating inside the microstructure in various directions. The healing capacity was evaluated using mice model and demonstrated faster wound closure and matured bilayer-skin formation.Conclusion: The outcomes convey that all formulated functionalised hydrogels delivered the optimum features to be used as a provisional biotemplate for skin tissue engineering purposes. The findings above indicated that injectable funtionalised-hydrogels have excellent physicochemical properties and acceptable biocompatibility as a rapid acellular treatment for future use in irregular deep cutaneous chronic wounds.Acknowledgement: This work was supported by Skim Geran Penyelidikan Fundamental (FRGS), Ministry of Higher Education, Malaysia [grant code: FRGS/۱/۲۰۲۰/STG۰۵/UKM/۰۲/۷] and Geran Fundamental Fakulti Perubatan (GFFP), Faculty of Medicine, Universiti Kebangsaan Malaysia [grant codes: FF-۲۰۲۰-۰۱۷ & FF-۲۰۲۱-۱۶۴].

کلیدواژه ها:

Biomaterials ، Tissue Engineering ، thermoresponsive ، bioprinting