Nanoengineered oxygen-releasing polymeric scaffold with sustained release of dexamethasone for bone regeneration.

Maintaining the continuous oxygen supply and proper cell growth before blood vessel ingrowth at the bone defect site are considerably significant issues in bone regeneration. Oxygen-producing scaffolds can supply oxygen and avoid hypoxia leading to expedited bone regeneration. Herein, first oxygen-producing calcium peroxide nanoparticles (CPO NPs) are synthesized, and subsequently, the various amounts of synthesized CPO NPs (0.1, 0.5, and 1 wt/v%) loaded in the scaffold composite, which is developed by simple physical blending of chitosan (CS) and polycaprolactone (PCL) polymers. To deliver the synergistic therapeutic effect, dexamethasone (DEX), known for its potential anti-inflammatory and osteogenic properties, is loaded into the nanocomposite scaffolds. The extensive physicochemical characterizations of nanocomposite scaffolds confirm the successful loading of CPO NPs, adequate porous morphology, pore size, hydrophilicity, and biodegradability.In vitro, biological studies support the antibacterial, hemocompatible, and cytocompatible (MG-63 and MC3T3-E1 cells) nature of the material when tested on respective cells. Field emission scanning electron microscopy and energy-dispersive x-ray spectroscopy confirm the successful biomineralization of the scaffolds. Scaffolds also exhibit the sustained release of DEX and efficient protein adsorption. This study revealed that a nanoengineered scaffold loaded with CPO NPs (PCL/CS/DEX/CPO 3) is a suitable candidate for bone tissue regeneration.

Pathophysiology to advanced intra-articular drug delivery strategies: Unravelling rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most prevalent life-long autoimmune diseases with an unknown genesis. It primarily causes chronic inflammation, pain, and synovial joint-associated cartilage and bone degradation. Unfortunately, limited information is available regarding the etiology and pathogenesis of this chronic joint disorder. In the last few decades, an improved understanding of RA pathophysiology about key immune cells, antibodies, and cytokines has inspired the development of several anti-rheumatic drugs and biopharmaceuticals to act on RA-affected joints. However, life-long frequent systemic high doses of commercially available drugs are currently a limiting factor in the efficient management of RA. To address this issue, various single and double-barrier intra-articular drug delivery systems (IA-DDSs) such as nanocarriers, microparticles, hydrogels, and particles-hybrid hydrogel composite have been developed which can exclusively target the RA-affected joint cavity and release the precisely controlled therapeutic drug concentration for prolonged time whilst avoiding the systemic toxicity. This review provides a comprehensive overview of the pathogenesis of RA and discusses the rational design and development of biomaterials-based novel IA-DDs, ranging from conventional to advanced systems, for improved treatment of RA. Therefore, this review aims to unravel the pathophysiology of rheumatoid arthritis and explore cutting-edge IA-DD strategies exploiting biomaterials. It offers researchers a consolidated and up-to-date resource platform to analyze existing knowledge, identify research gaps, and contribute to the scientific literature.

Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing.

Biological macromolecules are excellent materials for wound dressing owing to their similar structure to the extracellular matrix and adjustable physicochemical properties. This research focuses on fabricating biological macromolecule-based hydrogel with desirable antibacterial, antioxidant, controlled drug release, cytocompatibility, and wound healing properties. Herein, different concentrations of nanoceria (NC) and flurbiprofen (FLU) drug-loaded gellan gum/gelatin (GG/Ge) based dual crosslinked (Ionic and EDC/NHS coupling) hydrogels were engineered. All fabricated hydrogels were hydrophilic, biodegradable, good strength, porous, antioxidant, hemocompatible and cytocompatible. Among all, hydrogel loaded with 500 µg/ml NC (GG/Ge/NC@FLU) exhibited desirable antioxidant, antibacterial (killed Staphylococcus aureus and Escherichia coli within 12 h), hemocompatible, cytocompatible, supports oxidative-stressed L929 cell growth and acted as a controlled release matrix for FLU, following Fickian diffusion, Peppas Sahlin and Korsmeyer-Peppas drug release models. Furthermore, nanocomposite hydrogel (GG/Ge/NC@FLU)-treated wounds of rats on day 14 demonstrated significantly higher collagen synthesis, nearly 100 % wound contractions, and efficiently decreased the expression of TNF-α and IL-1 while increasing the production of IL-10 and TNF-ß3, indicating antiinflammatory activity, and effectively reduced the expression of VEGF gene indicating effective angiogenesis than all other controls. In conclusion, the fabricated multifunctional GG/Ge/NC@FLU nanocomposite hydrogel shows promising potential for effectively treating full-thickness wound healing in a rat model.