ABSTRACT
Recent advances in additive manufacturing have led to the development of innovative solutions for tissue regeneration. Hydrogel materials have gained significant attention for burn wound treatment in clinical practice among various advanced dressings due to their soothing and moisturizing activity. However, prolonged healing, pain, and traumatic removal due to the lack of long-term wound hydration are some of the challenges in the treatment of second-degree burn wounds. In this study, 3D-printed dressings were fabricated using gelatin, alginate, and bioactive borate glass (BBG) using an extrusion-based bioprinter. After ionic crosslinking, the 3D-printed dressings were characterized for mechanical properties, degradation rate, hydration activity, and in vitro cell viability using human fibroblasts. The results demonstrated that in 3D-printed dressings with 20 wt% BBG, Young's modulus increased by 105%, and 10-day degradation rate decreased by 62%. Addition of BBG prevented the burst release of water from hydrogel dressings and enabled the continuous water release for up to 10 days, which is crucial in treating second-degree burn wounds. 3D-printed hydrogel dressings with BBG showed long-term cell viability that can be a result of the accumulative release of therapeutic ions from BBG particulate. The in vivo wound healing functionality of the dressings was investigated using a rat model with a second-degree burn wound. Our animal study showed that the 3D-printed dressings with BBG exhibited faster wound closure, non-adhesive contact, non-invasive debridement, and non-traumatic dressing removal. Histological analysis suggested that 3D-printed dressings contributed to more uniform re-epithelialization and tissue remodeling compared to the non-printed hydrogels of the same compositions. Critically, 3D-printed dressings with BBG led to significant regeneration of hair follicles compared to the 3D-printed hydrogel, non-printed hydrogel, and the control groups. The superior outcome of the 3D-printed hydrogel-BBG20 dressings can be attributed to the bioactive formulation, which promotes moist wound healing for longer time periods, and the non-adhesive porous texture of the 3D-printed dressings with increased wound-dressing interactions. Our findings provided proof of concept for the synergistic effect of bioactive formulation and the porous texture of the 3D-printed hydrogel dressings incorporated with BBG on continuous water release and, consequently, on second-degree burn wound healing.
ABSTRACT
Burn wound treatment is still a clinical challenge due to the severity of tissue damage and dehydration. Among various wound dressings, hydrogel materials have gained significant attention for burn wound treatment in clinical practice due to their soothing and moisturizing activity. In this study, 3D-printed dressings were fabricated using clinically relevant hydrogels for deep partial-thickness burn (PTB) wounds. Different ratios of gelatin and alginate mixture were 3D-printed and examined in terms of rheological behavior, shear thinning behavior, mechanical properties, degradation rate, and hydration activity to tune the hydrogel composition for best functionality. The cell-laden dressings were bioprinted to evaluate the effect of the gelatin: alginate ratio on the proliferation and growth of human dermal fibroblasts. The present findings confirm that the higher alginate content is associated with higher viscosity and Young's modulus, while higher gelatin content is associated with faster degradation and higher cell viability. Together, the 3D-printed dressing with 75% gelatin and 25% alginate showed the best tradeoff between mechanical properties, hydration activity, and in vitro biological response. Findings from in vivo test using the most effective dressing showed the positive effect of 3D-printed porous pattern on wound healing, including faster wound closure, regenerated hair follicles, and non-traumatic dressing removal compared to the non-printed hydrogel with the same composition and the standard of care. Results from this research showed that 3D-printed dressings with an adequate gelatin: alginate ratio enhanced wound healing activity for up to 7 days of moisture retention on deep PTB wounds.
