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.

Effect of Laser Therapy on Postoperative Pain and Endodontic Retreatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Root canal re-treatment (RCR) cases are considered some of the most challenging cases in the field of endodontics, as they are mostly associated with various iatrogenic errors such as ledge formation, incomplete biomechanical preparation, file separation, and incomplete obturation. These iatrogenic errors lead to defective niches within root canals that may act as reservoirs for various viable microorganisms. Such residual microbial niches may cause postoperative pain even after thorough debridement and reshaping the canals, ultimately leading to a poor prognosis for the tooth. Nowadays, prevention of postoperative pain in re-treatment cases and prognosis are effectively managed by photobiomodulation therapy (PBMT). METHOD: Relevant studies in the English language published before November 2022 were identified using electronic databases like PubMed, SCOPUS, and EBSCO to conduct bibliographic research. This systematic review is based on 3 studies that were found eligible as per the inclusion and exclusion criteria. This systematic review is in accordance with PRISMA guidelines. RESULTS: The systematic review indicated a positive impact by significantly decreasing postoperative pain in RCR cases when treated with PBMT. The variation was statistically significant at 24 hours (P = .0002), 48 hours (P = .03), and 72 hours (P = .02). The mean difference at 24 hours was 0.65 (95% CI, 0.32-0.99), at 48 hours was 0.46 (95% CI, 0.05-0.87), and at 72 hours was 0.40 (95% CI, 0.07-0.74). There was no statistical heterogenicity at 24 hours (P > .05), but a medium heterogenicity was observed at 48 hours and 72 hours. PRACTICAL IMPLICATION: PBMT or low-level laser therapy has shown superior results as compared to the conventional pharmacologic approach in postoperative pain management in RCR cases.

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.

Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel.

Developing an ideal vitreous substitute/implant is a current challenge. Moreover, implants (e.g., heart valves and vitreous substitutes), are associated with a high risk of bacterial infection when it comes in contact with cells at implant site. Due to infection, many implants fail, and the patient requires immediate surgery and suffers from post-operative problems. To overcome these problems in vitreous implants, we developed a bacterial resistant vitreous implant, where meropenem (Mer), an antibiotic, has been incorporated in a hydrogel prepared by crosslinking HA (deacetylated sodium hyaluronate) with 4-arm-polyethylene-succinimidyl-carboxymethyl-ester (PESCE). The HA-PESCE hydrogel may serve as a suitable artificial vitreous substitute (AVS). The pre-gel solutions of HA-PESCE without drug and with the drug are injectable through a 22 G needle, and the gel formation occurred in approx. 3 min: it indicates its suitability for in-situ gelation through vitrectomy surgery. The HA-PESCE hydrogel depicted desired biocompatibility, transparency (>90 %), water content (96 %) and sufficient viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. The HA-Mer-PESCE hydrogel showed improved biocompatibility, suitable transparency (>90 %), high water content (96 %), and suitable viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. Further, hydrogel strongly inhibits the growth of bacteria E.coli and S.aureus. The drug loaded hydrogel showed sustained in-vitro drug release by the Fickian diffusion-mediated process (by Korsmeyer-Peppas and Peppas Sahlin model). Thus, the developed hydrogel may be used as a potential bacterial resistant AVS.

Nanoceria laden decellularized extracellular matrix-based curcumin releasing nanoemulgel system for full-thickness wound healing.

Decellularized extracellular matrix (ECM) has been widely used for wound healing. But, ECM failed to integrate tissue and restore the tissue function properly, when elevated levels of free radicals and biofilm formation occur at the wound site. Here, nanoemulgel systems were fabricated, considering the combinatorial approach of nanotechnology (nanoceria and curcumin nanoemulsion) and ECM gel of goat small intestine submucosa. The curcumin was encapsulated in the nanoemulgel system to enhance bioavailability in terms of antibacterial, antioxidant, sustained release and permeation at the wound site. Nanoceria was also incorporated to enhance the antibacterial, antioxidant and wound healing properties of the fabricated nanoemulgel formulation. All the formulations were porous, hydrophilic, biodegradable, antioxidant, antibacterial, hemocompatible, biocompatible, and showed enhanced wound healing rate. The formulation (DG-SIS/Ce/NC) showed the highest free radicals scavenging capacity and antibacterial property with prolonged curcumin release (62.9% in 96 h), skin permeability (79.7% in 96 h); showed better cell growth under normal and oxidative-stressed conditions: it also showed full-thickness wound contraction (97.33% in 14 days) with highest collagen synthesis at the wound site (1.61 µg/mg in 14 days). The outcomes of this study suggested that the formulation (DG-SIS/Ce/NC) can be a potential nanoemulgel system for full-thickness wound healing application.

Study of Sick Euthyroid Syndrome in Organophosphate Poisoning.

Sick euthyroid syndrome is abnormal findings of thyroid function tests that occur among patients with non thyroid illness with reduced level of hormones like T3 (Triiodothyronine) among acute illness of poisoning and can be detected in blood within 2 hours after acute illness. As the disease progress there is severe manifestation of syndrome associated with hypothyroidism specially with T3 and T4 while, the level of TSH are slightly elevated or are not influenced. The Present study was carried out to assess the incidence of sick euthyroid syndrome in organophosphate poisoning as well to assess the socio demographic and clinical profile of patients with organophosphate poisoning. MATERIAL: This study was carried out at a tertiary care center for period of one year from January to December 2020 in a sample size of 74 patients(>18 years) admitted in ICU with the history of Organophosphate poisoning. Hemogram and thyroid profile and liver and kidney function of the patients were studied including assessment of gastric aspirates. OBSERVATION: Out of 74 patients, majority of them were males (62%) in the age group of 21 to 30 years (42%), with organophosphate (64%) followed by carbamates (15%). The incidence of sick euthyroid syndrome with organophosphate poisoning was 53%. The mean serum cholinesterase in poisoning was 913±15.3. The factors which are statistically associated with sick euthyroidism were Male (20 to 40 years), low serum cholinesterase, no prior treatment, ECG changes and miosis. CONCLUSION: Organophosphate poisoning is more common among young males with incidence of sick euthyroid being quite high among these patients. Pesticide poisoning is more common among young adult males in the age group of 20 to 40 years with the motive of suicidal tendency. The incidence of euthyroidism among organophosphate poisoning is quite high. The biochemical investigations in our study shows an elevation in organophosphate poisoning. This can be used as an indicator to assess the severity of poisoning. The serum cholinesterase and thyroid investigation can also be used as prognostic markers in assessment of severity of organophosphate poisoning. Hence, we conclude that biochemical markers and thyroid investigations helps in assessing mortality and prompt treatment of organophosphate poisoning.

Development of decellularization protocol for caprine small intestine submucosa as a biomaterial.

Decellularized animal tissues have been proven to be promising biomaterials for various tissue engineering (TE) applications. Among various animal tissues, small intestine submucosa (SIS) has gained attention of many researchers due to its easy availability from the abattoir waste, excellent physicochemical and biological characteristics of a good biomaterial. In this study, Caprine SIS was decellularized to get decellularized caprine SIS (DG-SIS). For decellularization, several physical, chemical and enzymatic protocols have been described in the literature. To optimize the decellularization of caprine SIS, several decellularization protocol (DP), including an in-house developed by us, had been attempted, and effect of the different DPs on the obtained DG-SIS were assessed in terms of decellularization, physiochemical and biological properties. All the DPs differ in terms of decellularization, but three DPs where ionic detergent like sodium dodecyl sulphate (SDS) has been used, largely affect the native composition (e.g. glycosaminoglycans (GAGs)), biological properties and other physiochemical properties of the G-SIS as compared to the DP that uses hypertonic solution of potassium iodide (KI) and non-ionic detergent (TritonX-100). The obtained DG-SISs were fibrous, hemocompatible, biocompatible, hydrophilic, biodegradable and exhibited significant antibacterial activity. Therefore, the DG-SIS will be a prospective biomaterial for TE applications.

Curcumin in decellularized goat small intestine submucosa for wound healing and skin tissue engineering.

Biomaterials derived from extracellular matrices (ECMs) were extensively used for skin tissue engineering and wound healing. ECM is a complex network of biomolecules (e.g., proteins), which provide organizational support to cells for growth. Thus, ECM could be an ideal biomaterial for fabricating the scaffold. However, oxidative stress and biofilm formation at the wound site remains a major challenge that could be neutralized using herbal ingredients (e.g., curcumin). In this study, ECM was extracted from the biowaste of the goat abattoir by using decellularization. The goat small intestine submucosa (G-SIS) is decellularized to obtain the decellularized G-SIS (DG-SIS) and curcumin (in different concentrations) was incorporated in the DG-SIS to fabricate curcumin-embedded DG-SIS scaffolds. Changes brought by increasing the concentrations of the curcumin in DG-SIS were observed in various properties, including free radical scavenging and antibacterial properties. Results depicted that the scaffolds are porous, biodegradable, biocompatible, antibacterial, and hydrophilic and showed sustained release of curcumin. Besides, it showed free radicals scavenging property. The porosity and hydrophilicity of the scaffolds were decreased with an increase in the curcumin content. However, biodegradability, free radical scavenging, biocompatibility, and antibacterial properties of the scaffolds increased with an increase in the curcumin content. The DG-SIS scaffold containing 1 wt % of curcumin may be a potential biomaterial for wound-healing and skin tissue engineering.

A highly transparent tri-polymer complexin situhydrogel of HA, collagen and four-arm-PEG as potential vitreous substitute.

There is a requirement of removal and replacement of vitreous for various ophthalmic diseases, e.g. retinopathy and retinal detachment. Clinical tamponades, e.g. silicone oil and fluorinated gases are used but limited due to their toxicity and some complications. A lot of polymer-based materials have been tested and proposed as vitreous substitute, but till date, there is no ideal vitreous substitute available. Thus, it requires to develop an improved vitreous substitute which will be highly suitable for vitreous replacement. We have developed tri-polymer complexin situhydrogels by crosslinking among hyaluronic acid (HA), collagen (Coll) and four-arm-polyethylene glycol (PEG). All the developed hydrogels are biocompatible with NIH 3T3 mouse fibroblast cells, having pH in the range 7-7.44 and refractive index in the range 1.333-1.345. The developed hydrogels are highly transparent, showing transmittance >97%. FTIR study shows that the hydrogel was crosslinked by amide bond formation between HA and PEG, and between Coll and PEG. The rheological study shows that all the developed hydrogels exhibit viscoelastic behavior and all the hydrogels have storage modulus values (>100 pa) which is greater than loss modulus values-indicating sufficient elasticity for vitreous application. The elastic nature of the hydrogel increases with the increase in PEG concentration. The gel is formed in between 2 and 3 min-indicating its applicationin situ. The viscosity of the developed hydrogels shows shear thinning behavior. The pre-gel solution of the hydrogel is injectable through a 22 G needle-indicating its applicationin situthrough vitrectomy surgery. All the hydrogels are hydrophilic and have water content of 96% approximately. Thus, the results show the positive properties for its application as a potential vitreous substitute.

Biomatrix from goat-waste in sponge/gel/powder form for tissue engineering and synergistic effect of nanoceria.

For tissue engineering (TE), decellularized matrices gained huge potential as they consist of natural biomolecules which help in cell attachment and proliferation. Among various animal tissues, goat tissue has gained least attention in spite of the fact that goat tissue is less susceptible to disease transmission as compared to cadaveric porcine and bovine tissue. In this study, goat small intestine submucosa (G-SIS) was isolated from goat small intestine (G-SI), a waste from goat-slaughterhouse, and decellularized to obtain decellularized G-SIS (DG-SIS) biomatrix in the form of powder, gel and sponge form, so that it can be used for healing various types of wounds. Further, nanoceria (NC), owing to its free radical scavenging, anti-inflammatory, antibacterial and angiogenic properties, was incorporated in the DG-SIS in to fabricate DG-SIS/NC nanobiocomposite scaffold, which may exhibit synergistic effects to accelerate tissue regeneration. The scaffolds were found to be hydrophilic, biodegradable, haemocompatible, biocompatible, antibacterial and showed free radical scavenging capability. The scaffold containing NC concentration (500 µg ml-1) depicted highest cell (fibroblast cells) adhesion, MTT activity and free radical scavenging as compared to the DG-SIS and other nanobiocomposite scaffolds. Thus, DG-SIS/NC3 (NC with concentration 500 µg ml-1) scaffold could be a potential scaffold biomaterial for skin TE application.

Vitreous substitutes: An overview of the properties, importance, and development.

Vitreous or vitreous humor is a complex transparent gel that fills the space between the lens and retina of an eye and acts as a transparent medium that allows light to pass through it to reach the photoreceptor layer (retina) of the eye. The vitreous humor is removed in ocular surgery (vitrectomy) for pathologies like retinal detachment, macular hole, diabetes-related vitreous hemorrhage detachment, and ocular trauma. Since the vitreous is not actively regenerated or replenished, there is a need for a vitreous substitute to fill the vitreous cavity to provide a temporary or permanent tamponade to the retina following some vitreoretinal surgeries. An ideal vitreous substitute could probably be left inside the eye forever. The vitreous humor is transparent, biocompatible, viscoelastic and highly hydrophilic; polymeric hydrogels with these properties can be a potential candidate to be used as vitreous substitutes. To meet the tremendous demand for the vitreous substitute, many scientists all over the world have developed various kinds of vitreous substitutes or tamponade agent. Vitreous substitutes, whatsoever developed till date, are associated with several advantages and disadvantages, and there is no ideal vitreous substitute available till date. This review highlights the polymer-based vitreous substitutes developed so far, along with their advantages and limitations. The gas-based and oil-based substitutes have also been discussed but very briefly.

Gelatin-alginate-cerium oxide nanocomposite scaffold for bone regeneration.

Worldwide the number of bone damage/fracture, due to traumatic and accidental injuries, has been growing exponentially. Currently available treatments for bone repairing are slow, and often full functional recovery is not achieved. During slow healing process, free radicals are generated at fractured site, which causes further delay in healing process. To overcome these problems, bone tissue engineering (BTE) based approaches, i.e., polymeric scaffolds loaded with free radical scavenging capabilities, seem to be a potential alternative. Cerium oxide nanoparticles (nanoceria, NC) show very good free radical scavenging capabilities. In this study, NC was incorporated in gelatin-alginate (GA) scaffolds to obtain nanocomposite scaffolds (GA-NCs) by freeze drying. Further, the effect of varying nanoceria concentration on the physicochemical and biological properties of the nanocomposite scaffolds has been evaluated. Field emission scanning electron microscopy (FESEM) images of the scaffolds revealed presence of interconnected pores. Furthermore, incorporation of NC has increased the mechanical properties, bio-mineralization, and decreased the swelling and in-vitro weight loss of the scaffolds. Additionally, GA-NCs depicts competent cell attachment, proliferation and viability. The results for osteogenic differentiation studies (i.e. ALP activity, RunX2 and osteocalcin expression) have indicated that GA-NCs scaffolds hold potential to assist differentiation of mesenchymal stem cells (MSCs) to osteoblast. Finally, the results for free radical scavenging functionality demonstrate that GA-NCs are capable of reducing free radicals. Thus, it could be stated that NC incorporated GA nanocomposite scaffold has vital importance for applications in bone tissue-engineering in future regenerative therapies.

Development of a nanocomposite scaffold of gelatin-alginate-graphene oxide for bone tissue engineering.

Bone damage, due to congenital defects, trauma and sports-related injuries, has become a foremost health problem all over the world. The present study involves fabrication of a nanocomposite scaffold of graphene oxide (GO), gelatin and alginate, with an aim of enhancing bone regeneration. The effect of varying concentration of GO on the scaffold properties was also determined. The incorporation of GO enhanced the compressive strength of the nanocomposite scaffolds significantly compared to the gelatin-alginate (GA) scaffold which is without GO. High % swelling (~700%) of the nanocomposite scaffold indicates its high hydrophilicity, which is suitable for tissue engineering. Slow biodegradation (~30% in 28 days) indicates its suitability for bone regeneration. In vitro studies, by seeding MG-63 cells over the nanocomposite scaffolds, revealed an enhancement in cell attachment and proliferation as compared to the GA scaffold: this indicates the positive effect of the GO on the scaffold properties which, in turn, can enhance bone regeneration. Cell differentiation studies, with the mesenchymal stem cells seeded scaffolds, revealed higher expression of osteoblast transcription factors (Runx2 and Osteocalcin) and alkaline phosphatase activity-indicating the scaffold to be a good osteoinductive material. Thus, the nanocomposite scaffold will be a potential scaffold for bone tissue engineering.

Reinforcing effect of graphene oxide reinforcement on the properties of poly (vinyl alcohol) and carboxymethyl tamarind gum based phase-separated film.

The current study deals with the preparation and the characterization of the PVA-CMT-GO films. The PVA-CMT film was translucent in nature and smooth to touch. The addition of GO resulted in the formation of agglomerated structures. XRD studies suggested that the incorporation of GO increased the average crystallite size. The mechanical properties of the films as determined by stress relaxation studies suggested that all the films were viscoelastic in nature. The drug release study showed a decrease in the amount of the drug release with the increase in the GO content. The PVA-CMT-GO films (without drug) showed certain degree of antimicrobial activity owing to the inherent antimicrobial property of GO. The drug loaded films also showed good antimicrobial property. It was found that the prepared films altered the cell proliferation of the human skin keratinocytes in a composition-dependent manner.

Magnetic nanoparticle incorporated oleogel as iontophoretic drug delivery system.

In this article, we validated the use of electric current as an external stimulus to induce an enhancement of drug release from magnetic nanoparticle (MNP) incorporated organogels (magnetogel) under iontophoretic conditions. For this purpose, we adopted a simple, two-step synthesis route to incorporate magnetic (Fe3O4) nanoparticles (MNP) and ciprofloxacin hydrochloride within the network of a soybean oil-based oleogel using stearic acid as gelator. We fabricated a series of MNP incorporated oleogels by varying the wt% of MNPs while keeping a constant weight ratio of soybean oil:stearic acid. The microstructures of the magnetogels were analyzed in MNP concentration-dependent manner by optical microscopy, powder X-ray diffraction, FTIR, mechanical, and electrical studies. Detailed analysis of the electrical properties revealed that the gel sample with a maximum proportion of MNP (S4) allowed the maximum passage of current through it among all the compositions. Under the iontophoretic environment of the active condition, we observed nearly 2.5 fold increase in cumulative drug release in case of sample S4 compared to the corresponding passive condition. These observations suggested that in future, our magnetogel formulation can be further developed as AC field induced 'remote controlled' agent for therapeutic application.

Synthesis and characterization of polyvinyl alcohol- carboxymethyl tamarind gum based composite films.

The present study delineates the synthesis of novel composite films using polyvinyl alcohol and carboxymethyl tamarind gum. The microscopic study results confirmed the formation of composite matrices. FTIR spectroscopy suggested the occurrence of hydrogen-bonding amongst the components of the films. The extent of hydrogen bonding was composition-dependent which reached a critical higher limit at a particular composition. At the critical composition, the instantaneous and the intermediate polymer relaxation time were longer. All the films were found to be viscoelastic in nature. The melting endotherm was also highest for the composition described above. Ciprofloxacin loaded films showed excellent antimicrobial property against E. coli, suggesting that the drug was released in its active form. Cell proliferation study using human keratinocytes suggested better cell proliferation in the CMT containing films as compared to the control (PVA only) film. In gist, the developed films can be explored for skin tissue engineering and drug delivery applications.