Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release.

Recently, a significantly greater clinical benefit has been reported with a combination of glucosamine sulfate and nonsteroidal anti-inflammatory drugs (NSAIDs) compared to either treatment alone for the growing osteoarthritis (OA) disease. So, this study introduces hydrogels using O-carboxymethyl chitosan (O-CMC, structurally akin glucosamine glycan), and Gelatin type A (GA) in a 1:2 ratio with ß-glycerophosphate (ßGPh) at varying percentages (5 %, 12.5 %, and 15 %). We show that hydrogel properties, adaptable for drug delivery or tissue engineering, can be fine-tuned based on OCMC:ßGPh ratio. CMC/GA/ßGPh-12.5 exhibited a swelling rate of 189 %, compressive stress of 164 kPa, and compressive modulus of 3.4 kPa. The self-healing hydrogel also exhibited excellent injectability through a 21-gauge needle, requiring only 5 N of force. Ibuprofen and Naproxen release from CMC/GA/ßGPh-12.5 and CMC/GA/ßGPh-15 of designed dimensions (bi-layer structures of different diameter and height) were measured, and drug release kinetics were estimated using mathematical equations (MATLAB and polyfit program). CMC/GA/ßGPh-12.5 demonstrated significant antibacterial effects against E. coli and S. aureus, a high cell survival rate of 89 % against L929 fibroblasts, and strong cell adhesion, all indicating biocompatibility. These findings underscore potential of these hydrogels as promising candidates for treating inflammatory diseases such as osteoarthritis.

Dexamethasone loaded injectable, self-healing hydrogel microspheresbased on UPy-functionalized Gelatin/ZnHAp physical network promotes bone regeneration.

Biopolymer-based injectable hydrogels provide great potential as bone tissue engineering (BTE) scaffolds on account of biocompatibility, and pore interconnectivity that enables delivery of cells and/or signaling molecules for bone repair. Recently, Gelatin hydrogels based on H-bonds were considered in response to concerns around the chemical crosslinking agents. In this study, a self-healing gelatin hydrogel with remarkable compressive and self-healing properties was prepared via formation of quadruple hydrogen bonds between ureidopyrimidinon functional groups, which were substituted on NH2 groups of gelatin(GelUPy). Degree of substitution controls properties of the resulting hydrogel from a shape- memory hydrogel (100% substitution), to a hydrogel (about 80%), to this self-healing hydrogel (about 40%). We report a strategy that adopts an emulsion synthesis approach to delivery of dexamethasone and Ca/Zn ions from injectable self-healing GelUPy hydrogel (GelUPy-ZnHApUPy-DEX), to induce osteogenic differentiation of adipose-derived stem cells, in vitro, and enhance bone regeneration in a cranial bone defect in a rat model. We show that key properties of the composite hydrogels, including mechanical properties, and release behavior of DEX are a match to the requirements of BTE. Overall, our results demonstrate that this self-healing gelatin approach is a promising strategy to enhance bone regeneration through a minimally invasive procedure.

Impact of supramolecular interactions on delivery of dexamethasone from a physical network of gelatin/ZnHAp composite scaffold.

Synthesis of a supramolecular composite hydrogel, a novel class of physical and dynamic hydrogels, is reported. The hydrogel comprised gelatin (Gel), Zn-doped nano-hydroxyapatite (nZnHAp), and dexamethasone disodium phosphate (DEX). nZnHAp was functionalized with ureidopyrimidinone (UPy; quadruple hydrogen-bond-forming groups). The nHAp, nZnHAp, and nZnHApUPy were characterized by FTIR, EDX, SEM, and TGA analysis. Gelatin was also functionalized with UPy groups (GelUPy), and the nanocomposites were prepared in solution (GelUPy/nZnHApUPy). Dexamethasone was added to the composite hydrogels (15, 20, and 25 wt%), as an osteoinductive and anti-inflammation medicine (GelUPy/nZnHApUPy/DEX). The mechanical (in compression mode), rheological, and thermal properties of the GelUPy/nZnHApUPy/DEX were compared with those of GelUPy/nZnHAp/DEX. The GelUPy/nZnHApUPy/DEX series showed the maximum compressive modulus (about 841 KPa) for GelUPy/nZnHApUPy/DEX25% in the swollen state. DSC analysis indicated that Tg of the pure GelUPy decreased significantly upon composite preparation and drug loading from 160 °C for GelUPy, down to 107 °C for GelUPy/nZnHApUPy/DEX15%. In-vitro drug release studies confirmed sustained release of DEX over a period of 12 days for GelUPy/nZnHApUPy composites with no remarkable initial burst compared to that of the pure GelUPy. Overall, our data suggests that the DEX carrying supramolecular nanocomposite can be used as an osteogenic hydrogel scaffold for bone tissue engineering applications.