Normal and chronic wound healing is a global challenge. Electrotherapy has emerged as a novel and efficient technique for treating such wounds in recent decades. Hydrogel applied to the wound to uniformly distribute the electric current is an important component in wound healing electrotherapy. This study reports the development and wound healing efficacy testing of vitamin D entrapped polyaniline (PANI)-chitosan composite hydrogel for electrotherapy. To determine the morphological and physicochemical properties, techniques like scanning electron microscopy (SEM); differential scanning calorimetry; X-ray diffraction; fourier-transform infrared spectroscopy were used. Moreover, pH, conductance, viscosity, and porosity were measured to optimize and characterize the vitamin D entrapped PANI-chitosan composite hydrogel. The biodegradation was studied using lysozyme, whereas the water uptake ability was studied using phosphate buffer. Ethanolic phosphate buffer was used to perform the vitamin D entrapment and release study. Cell adhesion, proliferation, and electrical stimulation experiments were conducted by seeding dental pulp stem cells (DPSC) into the scaffolds and performing (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay; SEM images were taken to corroborated the proliferation results. The wound healing efficacy of electrotherapy and the developed hydrogel were studied on excision wound healing model in rats, and the scarfree wound healing was further validated by histopathology analysis. The composition of the developed hydrogel was optimized to include 1% w/v PANI and 2% w/v of chitosan composite. This hydrogel showed 1455 μA conduction, 98.97% entrapment efficiency and 99.12% release of vitamin D in 48 hrs. The optimized hydrogel formulation showed neutral pH of 6.96 and had 2198 CP viscosity at 26°C. The hydrogel showed 652.4% swelling index and 100% degradation in 4 weeks. The in vitro cell culture studies performed on hydrogel scaffolds using DPSC and electric stimulation strongly suggested that electrical stimulation enhances the cell proliferation in a three-dimensional (3D) scaffold environment. The in vivo excision wound healing studies also supported the in vitro results suggesting that electrical stimulation of the wound in the presence of the conducting hydrogel and growth factors like vitamin D heals the wound much faster (within 12 days) compared to non-treated control wounds (requires 21 days for complete healing). The results strongly suggested that the developed PANI-chitosan composite conducting hydrogel acts effectively as an electric current carrier to distribute the current uniformly across the wound surface. It also acted as a drug delivery vehicle for delivering vitamin D to the wound. The hydrogel provided a moist environment, a 3D matrix for free migration of the cells, and antimicrobial activity due to chitosan, all of which contributed to the electrotherapy’s faster wound healing mechanism, confirmed through the in vitro and in vivo experiments.

Vitamin D is a commonly used bone modulator in regenerative medicine. Several modalities have been explored for the delivery of vitamin D including nanoparticles and scaffold. The present study aimed to assess the potential use of a bio-degradable chitosan scaffold for the delivery of vitamin D. The objectives included fabrication of a bio-degradable chitosan scaffold, integration of vitamin D into the scaffold, characterization of the vitamin D integrated scaffold. Characterization was carried out using, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The structure of the scaffold was assessed by scanning electron microscopy. The scaffold was placed in phosphate buffer saline and the release duration of vitamin D was observed using UV spectrophotometry. Dental pulp mesenchymal stem cells were added to the scaffold to study the scaffold associated toxicity and the functionality of the scaffold released vitamin D. The vitamin D release period from the scaffold was estimated to be for 80 hrs. MTT assay of the stem cells was comparable to that of the control group (stem cells cultured in media) inferring that the scaffold is not toxic towards the stem cells. The positive alizarin red S staining, a higher expression of alkaline phosphatase, osteocalcin, and RunX2 confirmed the functional capability (osteogenic differentiation of the stem cells) of the released vitamin D. Based on the data from the present study, it can be inferred that chitosan scaffold can be used for the sustained delivery of functional vitamin D for 3–5 days.

This work illustrates a novel method of fabrication of polymeric microneedle (MN) construct using bees wax as mould and development of coated polymeric MNs for drug delivery. A novel method of MN fabrication using bees wax as mould was established. The porous chitosan MN arrays were fabricated and coated with polylactic acid (PLA). The optimized MN arrays were coated with bovine serum albumin (BSA). The MNs were subjected to physiochemical and tensile strength characterization, followed by drug release study. The skin penetration and irritation study were performed in vivo in Wistar Albino rats. The constructed MN arrays contain MNs with 0.9 mm length, 600 μm width at the base, 30-60 μm diameter at the tip, and 1.5 mm distance between 2 needles. These MNs patch was having good mechanical strength (0.72 N/needle) and tensile strength 15.23 Mpa. The MN array patch had 6.26% swelling index and 98.5% drug release was observed on the 50th hr. Good penetration and no skin irritation was observed for optimized MN batch. Polymeric MN arrays were successfully developed using bees wax mould and were successfully coated with PLA to deliver the BSA through skin epidermis layer.

A microporous hydrogel was developed using sodium alginate (alg) and 4-aminosalicylic acid (4-ASA). The synthesized hydrogel was characterized using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), Carbon-13 nuclear magnetic resonance (¹³C-NMR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Additonal carboxyl and hydroxyl functional groups of 4-ASA provided significant lubrication and stress-triggered sol-gel transition to the conjugated hydrogel. In addition, cytotoxicity analysis was undertaken on the conjugated hydrogel using human dermal fibroblast-adult (HDFa) cells, displaying non-toxic characteristics. Drug release profiles displaying 49.6% in the first 8 h and 97.5% within 72 h, similar to the native polymer (42.8% in first 8 h and 90.1% within 72 h). Under applied external stimuli, the modified hydrogel displayed significant gelling properties and structure deformation/recovery behaviour, confirmed using rheological evaluation (viscosity and thixotropic area of 8095.3 mPas and 26.23%, respectively). The modified hydrogel, thus, offers great possibility for designing smart synovial fluids as a biomimetic aqueous lubricant for joint-related injuries and arthritis-induced conditions. In addtion, the combination of thixotropy, non-toxicity, and drug release capabilities enables potential viscosupplementation for clinical application.