Hydrogels can provide instant relief to pain and facilitate the fast recovery of wounds. Currently, the incorporation of medicinal herbs/plants in polymer matrix is being investigated due to their anti-bacterial and wound healing properties. Herein, we investigated the novel combination of chitosan (CS) and chondroitin sulfate (CHI) to synthesize hydrogels through freeze gelation process and enriched it with garlic (Gar) by soaking the hydrogels in garlic juice for faster wound healing and resistance to microbial growth at the wound surface. The synthesized hydrogels were characterized via Fourier-transform infrared spectroscopy (FTIR), which confirmed the presence of relevant functional groups. The scanning electron microscopy (SEM) images exhibited the porous structure of the hydrogels, which is useful for the sustained release of Gar from the hydrogels. The synthesized hydrogels showed significant inhibition zones against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, cell culture studies confirmed the cyto-compatibility of the synthesized hydrogels. Thus, the novel hydrogels presented in this study can offer an antibacterial effect during wound healing and promote tissue regeneration.

Wound healing is a multifaceted biological process influenced by both intrinsic and extrinsic factors. The ability of Wnt signaling to activate cell proliferation appears to serve a central role in wound healing. Therefore, the direct activation of Wnt or inhibition of the Wnt antagonist could be an ideal approach for the stimulation of wound healing. This study aimed to investigate the underlying mechanism of small molecule-loaded nanofibrous matrix in inducing wound healing. Herein, a naturally derived small molecule, curcumin, was used to inhibit the GSK3-β, which is considered a negative regulator of the Wnt/β-catenin signaling pathway. The docking results demonstrated that curcumin makes a complex with GSK3-β at seven specific sites, thereby inhibiting its activity. Moreover, the stabilization of β-catenin appeared to be increased with the treatment of curcumin. Next, curcumin was incorporated in poly ε-caprolactone nanofibrous matrices for controlled–sustained drug release to induce cell function. Curcumin-loaded nanofibrous matrix not only enhanced fibroblast cell proliferation, but also induced the expression of the fibroblast growth factor (FGF) in vitro. Moreover, the in vivo results showed that these nanofibrous mats significantly induced wound closure in 12 mm critical-sized defect. Collectively, these results suggest that the developed nanofibrous matrix promotes impaired wound healing by modulating cell proliferation and enhancing FGF expression that promotes wound closure.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3β inhibitor) interaction with GSK-3β was determined using molecular docking and stabilization of β-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3β at Cys199 residue. Stabilization and nuclear translocation of β-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Hydrogels can provide instant relief to pain and facilitate the fast recovery of wounds. Currently the incorporation of medicinal herbs/plants in polymer matrix is being investigated due to their anti-bacterial and wound healing properties. Herein, we investigated the novel combination of chitosan (CS), chondroitin sulfate (CHI) and garlic (Gar) to synthesize hydrogels through freeze gelation process for faster wound healing and resistance to microbial growth at the wound surface. The synthesized hydrogels were characterized via Fourier transform infrared spectroscopy (FTIR), which confirmed the presence of relevant functional groups. The scanning electron microscopy (SEM) images exhibited the porous structure of the hydrogels, which is useful for the sustained release of Gar from the hydrogels. The synthesized hydrogels showed significant inhibition zones against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, cell culture studies confirmed the cyto-compatibility of the synthesized hydrogels. Thus, the novel hydrogels presented in this study can offer antibacterial effect during wound healing and promote tissue regeneration.