Copper-MOF and tannic acid-empowered composite cryogel as a skin substitute for accelerated deep wound healing.

The effective management of deep skin wounds remains a significant healthcare challenge that often deteriorates with bacterial infection, oxidative stress, tissue necrosis, and excessive production of wound exudate. Current medical approaches, including traditional wound dressing materials, cannot effectively address these issues. There is a great need to engineer advanced and multifunctional wound dressings to address this multifaceted problem effectively. Herein, a rationally designed composite cryogel composed of a Copper Metal-Organic Framework (Cu-MOF), tannic acid (TA), polyvinyl alcohol (PVA), and zein protein has been developed by freeze-thaw technique. Cryogels display a remarkable swelling capacity attributed to their interconnected microporous morphology. Moreover, dynamic mechanical behaviour with the characteristics of potent antimicrobial, antioxidant, and biodegradation makes it a desirable wound dressing material. It was further confirmed that the material is highly biocompatible and can release TA and copper ions in a controlled manner. In-vivo skin irritation in a rat model demonstrated that composite cryogel did not provoke any irritation/inflammation when applied to the skin of a healthy recipient. In a deep wound model, the composite cryogel significantly accelerates the wound healing rate. These findings highlight the multifunctional nature of composite cryogels and their promising potential for clinical applications as advanced wound dressings.

Stimuli Responsive Molecular Exchange of Structure Directing Agents on Gold Nanobipyramids: Cancer Cell Detection and Synergistic Therapeutics.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

DNA functionalized programmable hybrid biomaterials for targeted multiplexed applications.

With the advent of DNA nanotechnology, DNA-based biomaterials have emerged as a unique class of materials at the center of various biological advances. Owing to DNA's high modification capacity via programmable Watson-Crick base-pairing, DNA structures of desired design with increased complexity have been developed. However, the limited scalability, along with poor mechanical properties, high synthesis costs, and poor stability, reduced the adaptability of DNA-based materials to complex biological applications. DNA-based hybrid biomaterials were designed to overcome these limitations by conjugating DNA with functional materials. Today, DNA-based hybrid materials have attracted significant attention in biological engineering with broad application prospects in biomedicine, clinical diagnosis, and nanodevices. Here, we summarize the recent advances in DNA-based hybrid materials with an in-depth understanding of general molecular design principles, functionalities, and applications. Finally, the challenges and prospects associated with DNA-based hybrid materials are discussed at the end of this review.

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.

Technological Interventions Enhancing Curcumin Bioavailability in Wound-Healing Therapeutics.

Wound healing has been a challenge in the medical field. Tremendous research has been carried out to expedite wound healing by fabricating various formulations, some of which are now commercially available. However, owing to their natural source, people have been attracted to advanced formulations with herbal components. Among various herbs, curcumin has been the center of attraction from ancient times for its healing properties due to its multiple therapeutic effects, including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, neuroprotective, and radioprotective properties. However, curcumin has a low water solubility and rapidly degrades into inactive metabolites, which limits its therapeutic efficacy. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, and keep its bioavailability and effectiveness. Different formulations with curcumin have been synthesized, and exist in the form of various synthetic and natural materials, including nanoparticles, hydrogels, scaffolds, films, fibers, and nanoemulgels, improving its bioavailability dramatically. This review discusses the advances in different types of curcumin-based formulations used in wound healing in recent times, concentrating on its mechanisms of action and discussing the updates on its application at several stages of the wound healing process. Impact statement Curcumin is a herbal compound extracted from turmeric root and has been used since time immemorial for its health benefits including wound healing. In clinical formulations, curcumin shows low bioavailability, which mainly stems from the way it is delivered in the body. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, while maintaining its bioavailability and therapeutic efficacy. This review offers an overview of the advanced technological interventions through tissue engineering approaches to efficiently utilize curcumin in different types of wound healing applications.

Multicomponent decellularized extracellular matrix of caprine small intestine submucosa based bioactive hydrogel promoting full-thickness burn wound healing in rabbits.

Effective treatment for full-thickness burn wounds has remained challenging for clinicians. Among various strategies, extracellular gel-based dressing materials have gained attention to promote effective and rapid wound healing. These gel-based materials are porous and have antioxidant, antibacterial, hydrophilic, biodegradation, and biocompatible properties and hence can be used to alleviate burn wound healing. In concurrence with these findings, the present study evaluates thermo-responsive and self-assembled decellularized extracellular matrix (ECM) of caprine small intestine submucosa (DG-SIS) gel-based dressing material for burn wound healing. To expedite healing and efficiently tackle excessive free radicals and bioburden at the burn wound site, DG-SIS gel is fortified with antibacterial components (zinc oxide nanoparticles; ZnO) and a potent antioxidant agent (Vitamin-C;Vt-C). ZnO- and Vt-C-enriched DG-SIS (DG-SIS/ZnO/Vt-C) gels significantly increased the antioxidant and antibacterial activity of the therapeutic hydrogel. Additionally, the fabricated DG-SIS/ZnO/Vt-C bioactive gel resulted in significant full-thickness burn wound contraction (97.75 % in 14 days), a lower inflammatory effect, and enhanced angiogenesis with the highest collagen synthesis (1.22 µg/mg in 14 days) at the wound site. The outcomes from this study demonstrate a synergistic effect of ZnO/Vt-C in the bioactive gel as an effective and inexpensive therapeutic approach for full-thickness burn wound treatment.

ß-Carotene laden antibacterial and antioxidant gelatin/polyglyceryl stearate nano-hydrogel system for burn wound healing application.

Worldwide, burn wounds are severe health issues prone to bacterial infections and challenging to treat with traditional wound dressings. Therefore, a highly desirable biological macromolecules-based wound dressing with good antioxidant, antibacterial, biocompatible, and a large surface area is required. Herein, aim to develop a biological macromolecules-based physically cross-linked gelatin/polyglyceryl stearate/graphene oxide (GPGO) hydrogel to treat burn wounds. Four sets of hydrogels were prepared by varying GO concentrations. FT-IR, FE-SEM, viscosity analysis, mechanical and thermal stability confirmed the successful preparation of hydrogels with desired properties. Further, ß-carotene (0.5 mg/mL) was encapsulated in hydrogels to enhance the antioxidant activity, and a cumulative release as well as kinetics at pH 6.4 and 7.4 was performed. With an increase in GO concentration, hydrogels showed sustained release of ß-carotene. Among all, GPGO-3 ß hydrogel showed the highest antioxidant potency (57.75 %), hemocompatible (<5 %), cytocompatible (viable with NIH 3T3 cells), cell migration, proliferation, and in vitro wound healing. Also, GPGO-3 ß hydrogel showed efficient antibacterial activity (%inhibition of 85.5 % and 80.2 % and zone of 11 mm and 9.8 mm against S. aureus and E. coli). These results demonstrated the ability of GPGO-3 ß hydrogel as a promising candidate for burn wound healing applications.

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.

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment.

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.

Comprehensive Evaluation of Degradable and Cost-Effective Plasmonic Nanoshells for Localized Photothermolysis of Cancer Cells.

Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 µg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.

Cefuroxime conjugated chitosan hydrogel for treatment of wound infections.

Hydrogels are excellent drug delivery systems for the treatment of chronic wound infections. However, the problem of high burst release still remains a challenge that needs to be tackled. In terms of antibiotic release from the hydrogels, as the drug payload depletes it could act as a substrate for bacterial seeding which can create a life-threatening condition. Therefore, to provide the sustained effect of an antibiotic at the localized site via hydrogel matrix, we prepared a chitosan (CS) hydrogel system in which cefuroxime (CEF) is covalently conjugated with chitosan polymer via an ester linkage. To prepare the cefuroxime conjugated chitosan hydrogel, the formulations were optimized using different concentrations of cefuroxime, 0% (CS/CEF_0), 5% (CS/CEF_5), 10% (CS/CEF_10) and 20% (CS/CEF_20) w/w of chitosan. Fourier Transform Infra-red Spectroscopy (FTIR) confirmed the conjugation of cefuroxime and chitosan. The drug release studies showed that the release of cefuroxime was higher in the phosphate buffer (pH 7.4) with esterase enzyme and alkaline medium (pH 10) compared to phosphate buffer (pH 7.4) alone. Hemolysis assay was performed to demonstrate the hemocompatibility of the prepared hydrogel samples. The cell viability study using the L929 fibroblast and MG63 osteosarcoma cell lines revealed that synthesized hydrogel is biocompatible. Furthermore, a potent antibacterial activity for the extended time period proved the biological efficacy of a hydrolyzed cefuroxime. Thus, CS/CEF_5, CS/CEF_10, and CS/CEF_20 hydrogels have a promising future in the treatment of chronic wound infections.

Plasmonic carbon nanohybrids for repetitive and highly localized photothermal cancer therapy.

Integrating metallic and non-metallic platform for cancer nanomedicine is a challenging task and bringing together multi-functionality of two interfaces is a major hurdle for biomaterial design. Herein, NIR light responsive advanced hybrid plasmonic carbon nanomaterials are synthesized, and their properties toward repetitive and highly localized photothermal cancer therapy are well understood. Graphene oxide nanosheets having thickness of ∼2 nm are synthesized using modified Hummers' method, thereafter functionalized with biodegradable NIR light responsive gold deposited plasmonic polylactic-co-glycolic acid nanoshells (AuPLGA NS, tuned at 808 nm) and NIR dye (IR780) to examine their repetitive and localized therapeutic efficacy as well resulting side effects to nearby healthy cells. It is observed that AuPLGA NS decorated graphene oxide nanosheets (GO-AuPLGA) and IR780 loaded graphene oxide nanosheets (GO-IR780) are capable in standalone complete photothermal ablation of cancer cells within 4 min. of 808 nm NIR laser irradiation and also without the aid of any anticancer drugs. However, GO-AuPLGA having the potential for repetitive photothermal treatment of a big tumor, ablate the cancer cells in highly localized fashion, without having side effects on neighboring healthy cells.

Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca2+. The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11µm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations.

Methotrexate loaded gellan gum microparticles for drug delivery.

Recently, polysaccharides based microparticles have been found to offer an attractive potential as a carrier in drug delivery field. In this study, bare gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion solvent diffusion method. The developed microparticles (MPs) were found discretely distributed in a spherical shape. MTX has been encapsulated in microparticles with 84.8 ±â€¯1.68% encapsulation efficiency (%EE) and 6.45 ±â€¯0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR) characterization of the MPs clearly indicated the physical encapsulation of MTX into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h. The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs) showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX-GG MPs are biocompatible.

Injectable methotrexate loaded polycaprolactone microspheres: Physicochemical characterization, biocompatibility, and hemocompatibility evaluation.

In this study, bare polycaprolactone microspheres (PCL MPs) and methotrexate (MTX) loaded PCL microspheres (MTX-PCL MPs) have been developed by oil-in-water emulsion solvent evaporation method using hydroxypropyl methylcellulose (HPMC) as an emulsifier. Encapsulation efficiency and loading capacity of methotrexate were found to be 51.28%±0.52 and 2.8%±0.06 respectively. Environmental scanning electron microscopy showed the PCL MPs and MTX-PCL MPs to have a spherical shape and smooth surface morphology. The mean size of microspheres (23µm) was found within injectability criteria. High-Resolution X-ray diffraction of microspheres revealed that PCL retained its semi-crystalline nature after processing in microspheres, but the drug looses its crystallinity. Fourier transmittance infrared spectroscopy and thermogravimetry analysis of the microspheres indicated that no physicochemical modification occurred. In vitro, MTX release study from MTX-PCL MPs in phosphate buffer saline (pH7.4) showed controlled release profile and only 31% of MTX released in 306h. The microspheres in lyophilized form are physicochemically stable for 8months. Furthermore, L929 cells treated with microspheres showed cell viability >80%. The different concentrations of microspheres found hemocompatible and did not affect the biconcave shape of red blood cells (RBCs). The physiochemical and biological evaluation of microspheres suggests their further use for drug delivery application.