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Synthetic bone grafts are being developed to overcome the limitations of conventional treatments for bone defects. In this study, we have fabricated bioactive binary and novel ternary interpenetrating polymer network (IPN) scaffolds using a combination of natural and synthetic polymers. The binary IPN scaffolds were prepared using Konjac glucomannan (KGM) and polyvinyl alcohol (PVA). In the novel ternary IPN scaffolds, polycaprolactone (PCL) was added to PVA and KGM. SEM images showed that these scaffolds were microporous with good interconnectivity. Compression testing confirmed that both the scaffolds are mechanically strong, with the ternary scaffolds having moduli comparable to the natural bone. In vitro cytocompatibility studies performed with NIH/3T3 fibroblasts cells and MG-63 osteosarcoma cells demonstrated the non-toxic and osseointegrating nature of the scaffolds. Confocal images confirmed that the cells migrated into the interconnected pores of the scaffolds. RT-PCR analysis showed that both binary and ternary scaffolds enhanced the expression of the major bone marker genes, viz., ALP, BMP-2, COLLAGEN-1, and OSTEOCALCIN. However, the expression of these osteogenic markers was significantly enhanced in the ternary scaffolds compared to the binary scaffolds. In vivo chick chorioallantoic membrane (CAM) assay shows that these scaffolds possess excellent pro-angiogenic properties. Hence, these desirable biological properties, coupled with the suitable physicochemical properties, make these IPN scaffolds ideal for treating bone defects.

In recent years, the therapeutic effects of phyto-principles have been appreciated for their promising effects on wound healing. Melia dubia (Malabar neem) possesses anti-cancer, anti-diabetic, anti-tumor, anti-inflammatory, antioxidant, antibacterial, and fungicidal properties. Here, we studied the wound healing efficacy of ethanolic extract of M. dubia leaves on cutaneous wound healing for the first time. The ethanolic extract of M. dubia was applied topically on the wounds of the experimental rats until the wounds heal completely. Wounds of the control rats were treated with PBS. Granulation tissues formed on wound surfaces of the excision wound were harvested on days 4 and 8 and analyzed to determine the total collagen and hexosamine content. Total collagen and hexosamine were significantly (p < .001) higher in M. dubia treated rats compared to control. The rate of wound closure was significantly higher (p < .001) and period of epithelialization was shorter in M. dubia treated rats. Incision wound tissue was used for the tensile strength measurement. Tensile strength was improved in M. dubia treated wound tissues. Results concluded that the topical application of ethanolic extracts of M. dubia improved the rate of wound contraction and tensile strength by increased synthesis of collagen.

Here, we have studied the efficacy of pullulan gel on wound healing by performing biochemical, biophysical and histological investigations. A 2 cm2 open excision wound was made on the dorsum of the rats and topically treated with 500 μL of pullulan gel. The control group was left untreated. The povidone-iodine (PI) ointment treated animals were considered as positive control. The granulation tissues formed were collected at different time point intervals and used for various biochemical, biophysical and histological analyses. Biochemical analyses revealed that pullulan gel significantly (p

The aim of this article was to develop silk protein (SF) and l-proline (LP) loaded chitosan-(CS) based hydrogels via physical cross linking for tissue engineering and wound healing applications. Silk fibroin, a biodegradable and biocompatible protein, and l-proline, an important imino acid that is required for collagen synthesis, were added to chitosan to improve the wound healing properties of the hydrogel. Characterization of these hydrogels revealed that CS/SF/LP hydrogels were blended properly and LP incorporated hydrogels showed excellent thermal stability and good surface morphology. Swelling study showed the water holding efficiency of the hydrogels to provide enough moisture at the wound surface. In vitro biodegradation results demonstrated that the hydrogels had good degradation rate in PBS with lysozyme. LP loaded hydrogels showed approximately a twofold increase in antioxidant activity. In vitro cytocompatibility studies using NIH 3T3 L1 cells showed increased cell viability (p

Treatment of chronic non-healing wounds in diabetes is still a major clinical challenge. Here, we have developed reduced graphene oxide (rGO) loaded isabgol nanocomposite scaffolds (Isab + rGO) to treat normal and diabetic wounds. rGO was synthesized by rapid reduction of graphene oxide (GO) under focused solar radiation. Then, rGO was uniformly dispersed into isabgol solution to prepare Isab + rGO nanocomposite scaffolds. These scaffolds were characterized using various physiochemical techniques. Isab + rGO nanocomposite scaffolds showed suitable cell viability, proliferation, and attachment. In vivo experiments were performed using Wistar rats to study the wound healing efficacy of these scaffolds in normal and diabetic rats. Results revealed that rGO stimulated collagen synthesis, collagen crosslinking, wound contraction, and reduced the wound re-epithelialization time significantly compared to control. Histology and immunohistochemistry analyses showed that Isab + rGO scaffold treatment enhanced angiogenesis, collagen synthesis, and deposition in treated wounds. Isab + rGO scaffold treatment also played a major role in shortening the inflammation phase and recruiting macrophages to enhance the early phase of wound healing. Overall, this investigation showed that Isab + rGO scaffold dressing could significantly accelerate the healing of normal and diabetic wounds.

We have developed a novel hydrogel composed of konjac glucomannan (KGM), human hair proteins (KER), and an ethanolic extract of Avena sativa (OAT) and evaluated its potential as a dressing material for diabetic wounds. KGM is an excellent biocompatible gelling agent that stimulates fibroblast proliferation and immunomodulation. Human hair proteins (KER) are biocompatible, biodegradable, and possess abundant cell adhesion sites. KER also promotes fibroblast attachment and proliferation, keratinocyte migration, and collagen expression, which can accelerate wound healing. OAT consists of oat β-glucans and several anti-inflammatory and antioxidant moieties that can reduce prolonged inflammation in chronic wounds. SEM images confirm the highly porous architecture of the scaffolds. When immersed in PBS, KGM+KER+OAT hydrogels absorb 7.5 times their dry weight. These hydrogels display a measured rate of degradation in lysozyme. KGM+KER+OAT hydrogels showed no significant cytotoxicity against NIH/3T3 fibroblasts. DAPI and SEM images obtained after 48h of cell culture illustrate the attachment and infiltration of fibroblasts. In vivo studies performed using a diabetic rat excision wound model showed that KGM+KER+OAT hydrogels significantly accelerated wound healing compared to the control and the KGM+KER hydrogels.

We have developed L-glutamic acid (LG) loaded chitosan (CS) hydrogels to treat diabetic wounds. Although literature reports wound healing effects of poly(glutamic acid)-based materials, there are no studies on the potential of L-glutamic acid in treating diabetic wounds. As LG is a direct precursor for proline synthesis, which is crucial for collagen synthesis, we have prepared CS + LG hydrogels to accelerate diabetic wound healing. Physiochemical properties of the CS + LG hydrogels showed good swelling, thermal stability, smooth surface morphology, and controlled biodegradation. The addition of LG to CS hydrogels did not alter their biocompatibility significantly. CS + LG hydrogel treatment showed rapid wound contraction compared to control and chitosan hydrogel. Period of epithelialization is significantly reduced in CS + LG hydrogel treated wounds (16 days) compared to CS hydrogel (20 days), and control (26 days). Collagen synthesis and crosslinking are also significantly improved in CS + LG hydrogel treated diabetic rats. Histopathology and immunohistochemistry results revealed that the CS + LG hydrogel dressing accelerated vascularization and macrophage recruitment to enhance diabetic wound healing. These results demonstrate that incorporation of LG can improve collagen deposition, and vascularization, and aid in faster tissue regeneration. Therefore, CS + LG hydrogels could be an effective wound dressing used to treat diabetic wounds.

This study explores the potential of gallic acid incorporated chitosan (CS/GA) 3D scaffolds for tissue engineering applications. Scaffolds were prepared by freezing and lyophilization technique and characterized. FTIR spectra confirmed the presence of GA in chitosan (CS) gel. DSC and TGA analysis revealed that the structure of chitosan was not altered due to the incorporation of GA, but thermal stability was significantly increased compared to the CS scaffold. SEM micrographs showed smooth, homogeneous, and microporous architecture of the scaffolds with good interconnectivity. CS/GA scaffolds exhibited approximately 90% porosity on average, increased swelling (600-900%) and controlled biodegradation (15-40%) in PBS (pH 7.4 at 37°C) with 1 mg/mL of lysozyme. CS/GA scaffolds showed 2-4 fold decrease in CFUs (p 0.05) for both gram positive and gram negative bacteria compared to the CS scaffold. Cytotoxicity of these scaffolds was evaluated using NIH 3T3 L1 fibroblast cells. CS/GA 0.25% scaffold showed similar viability with CS scaffold at 24 and 48 h. CS/GA scaffolds (0.5-1.0%) showed 60-75% viability at 24 h and 90% at 48 h. SEM images showed that an increased cell attachment was observed for CS/GA scaffolds compared to CS scaffolds. These findings authenticate that CS/GA scaffolds were cytocompatible and would be useful for tissue engineering applications.