This study presents the development of thiol–maleimide/thiol–thiol double self-crosslinking hyaluronic acid-based (dscHA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and dscHA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)–thiol as crosslinkers. The six resulting dscHA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G′) in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six dscHA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained dscHA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six dscHA hydrogels show promise as dermal fillers for various facial regions.

In this study, an ultrasound-assisted digestion method of a formic acid-decellularized extracellular matrix (dECM) of porcine skin was developed and optimized to form UdECM hydrogels for diabetic wound healing. Results demonstrated that ultrasonication improved the extraction rate of collagen from dECM samples, preserved the collagen content of dECM, reduced residual cells, and extracted greater DNA contents. Scanning electron microscope (SEM) analyses were performed, which demonstrated the optimal porosity on the surface and density of the cross-section in the hydrogel structure, which could control the release of growth factors embedded in UdECM hydrogels at desirable rates to boost wound healing. A wound-healing study was conducted with six different composite hydrogels, both empty materials and materials enriched with rat platelet-rich plasma (R-PRP), sacchachitin nanofibers (SCNFs), and TEMPO-oxidized sacchachitin in diabetic rats. The assessment based on scars stained with hematoxylin and eosin (H&E), Masson’s trichrome (MT), and a cluster of differentiation 31 (CD31) staining showed that the UdECM/SC/R-PRP treatment group had the most significant efficacy of promoting healing and even recovery of diabetic wounds to normal tissues. UdECM/R-PRP and UdECM/SCNFs demonstrated better healing rates than UdECM hydrogel scaffolds, which had only recovered 50% resemblance to normal skin. Treatment with both UdECM/TEMPO 050 and UdECM/TEMPO 050/R-PRP hydrogel scaffolds was ranked last, with even poorer efficacy than UdECM hydrogels. In summary, formulated UdECM and SCNF hydrogels loaded with PRP showed synergistic effects of accelerating wound healing and ultimately stimulating the wound to recover as functional tissues. This newly UdECM/SCNF composite hydrogel has promising potential for healing and regenerating diabetic wounds.