Cranioplasty involves the surgical reconstruction of cranial defects arising as a result of various factors, including decompressive craniectomy, cranial malformations, and brain injury due to road traffic accidents. Most of the modern decompressive craniectomies (DC) warrant a future cranioplasty surgery within 6-36 months. The conventional process of capturing the defect impression and polymethyl methacrylate (PMMA) flap fabrication results in a misfit or misalignment at the site of implantation. Equally, the intra-operative graft preparation is arduous and can result in a longer surgical time, which may compromise the functional and aesthetic outcomes. As part of a multicentric pilot clinical study, we recently conducted a cohort study on ten human subjects during 2019-2022, following the human ethics committee approvals from the participating institutes. In the current study, an important aspect of measuring the extent of bone remodelling during the time gap between decompressive craniectomy and cranioplasty was successfully evaluated. The sterilised PMMA bone flaps were implanted at the defect area during the cranioplasty surgery using titanium mini plates and screws. The mean surgery time was 90 ± 20 min, comparable to the other clinical studies on cranioplasty. No signs of intra-operative and post-operative complications, such as cerebrospinal fluid leakage, hematoma, or local and systemic infection, were clinically recorded. Importantly, aesthetic outcomes were excellent for all the patients, except in a few clinical cases, wherein the PMMA bone flap was to be carefully customized due to the remodelling of the native skull bone. The extent of physiological remodelling was evaluated by superimposing the pre-operative and post-operative CT scan data after converting the defect morphology into a 3D model. This study further establishes the safety and efficacy of a technologically better approach to fabricate patient-specific acrylic bone flaps with improved surgical outcomes. More importantly, the study outcome further demonstrates the strategy to address bone remodelling during the patient-specific implant design.
Morin is an antioxidant and anticancer flavonoid, extracted from natural sources, that may exert beneficial effects for several pathologies. Despite this, the administration of morin represents a challenge due to its low aqueous solubility. Mesoporous silica materials have emerged as biocompatible tools for drug delivery, as their pore size can be modulated for maximum surface area to volume ratio. In this contribution, we evaluate the ability of iron-modified mesoporous materials, for morin loading and controlled delivery. The SBA-15 and MCM-41 sieves were synthesized and modified with iron (metal content 4.02 and 6.27 % wt, respectivily). Characterization by transmission electron microscopy, XRD and UV-Vis revealed adequate pore size and agglomerates of very small metallic nanospecies (nanoclusters), without larger iron oxide nanoparticles. FT-IR spectra confirmed the presence of silanol groups in the solid hosts, which can interact with different groups present in morin molecules. SBA-15 materials were more efficient in terms of morin loading capacity (LC) due to their larger pore diameter. LC was more than 35% for SBA-15 materials when adsorptions studies were carried out with 9 mg of drug. Antioxidant activity were assayed by using DPPH test. Free iron materials presented a significate improvement as antioxidants after morin incorporation, reaching a scavenging activity of almost a 90%. On the other hand, in iron modified mesoporous materials, the presence of morin did not affect the scavenging activity. The results could be related with the formation of a complex between the flavonoid and the iron. Finally, biosafety studies using normal epithelial cells revealed that neither the loaded nor the unloaded materials exerted toxicity, even at doses of 1 mg/ml. These findings expand knowledge about mesoporous materials as suitable carriers of flavonoids with the aim of improving therapies for a wide range of pathologies.
Skin tissue engineering has gained significant attention as a promising alternative to traditional treatments for skin injuries. In this study, we developed 3D hydrogel-based scaffolds, Alginate, incorporating different concentrations of Curcumin and evaluated their properties, including morphology, swelling behavior, weight loss, as well as hemo- and cytocompatibility. Furthermore, we investigated the therapeutic potential of Alginate hydrogel containing different amounts of Curcumin using an in vitro wound healing model. The prepared hydrogels exhibited remarkable characteristics, SEM showed that the pore size of hydrogels was 134.64 μm with interconnected pores, making it conducive for cellular infiltration and nutrient exchange. Moreover, hydrogels demonstrated excellent biodegradability, losing 63.5% of its weight over 14 days. In addition, the prepared hydrogels had a stable release of curcumin for 3 days. The results also show the hemocompatibility of prepared hydrogels and a low amount of blood clotting. To assess the efficacy of the developed hydrogels, 3T3 fibroblast growth was examined during various incubation times. The results indicated that the inclusion of Curcumin at a concentration of 0.1 mg/mL positively influenced cellular behavior. The animal study showed that Alginate hydrogel containing 0.1 mg/mL curcumin had high wound closure(more than 80%) after 14 days. In addition, it showed up-regulation of essential wound healing genes, including TGFβ1 and VEGF, promoting tissue repair and angiogenesis. Furthermore, the treated group exhibited down-regulation of MMP9 gene expression, indicating a reduction in matrix degradation and inflammation. The observed cellular responses and gene expression changes substantiate the therapeutic efficacy of prepared hydrogels. Consequently, our study showed the healing effect of alginate-based hydrogel containing Curcumin on skin injuries.
Bletilla striata polysaccharide (BSP) was added to curdlan to form a blend hydrogel through a simple heating-cooling procedure to improve the hydrophilicity and healing efficacy of curdlan-based hydrogel used in wound healing. We explored the interplay between BSP and curdlan, studied how BSP concentration affects the physical properties and microstructures of hydrogels, and examined the biocompatibility and healing properties of the blend hydrogel. It was proved that the hydrogel framework was primarily formed by ordered arranged curdlan molecules, with BSP uniformly dispersed and intertwined with curdlan through hydrogen bonding. This effectively improved its hydrophilicity and strengthened the microstructure. Curdlan was found to be compatible with BSP. The blend hydrogel B3Cd3 (containing 1.5% BSP and 1.5% curdlan, w/v) was identified as the optimal formulation based on its higher water adsorption, water retention, thermal stability and interconnected microstructure, and was thus selected for further research. In vitro experiments revealed the highest cell viability of L929 in B3Cd3 extracts compared to those extracts of single-component curdlan hydrogel (Cd). In vivo, animal studies indicated that the B3Cd3 accelerated wound healing compared to the control group by improving re-epithelialization and blood vessel regeneration. On Days 3 and 11, the therapeutic benefits of B3Cd3 exceeded those of the Cd group, and no significant differences were observed in wound healing rates between the B and B3Cd3 groups from Day 7. The study proves that BSP enhances the physical and healing properties, as well as cell proliferation, of the curdlan-based hydrogel. The blend hydrogel B3Cd3, with its exceptional properties, holds potential for future application as a material for non-infected wound healing.
In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine.