MULTIFUNCTIONAL WOUND HEALING DEVICE WITH CONTROLLED DRUG DELIVERY AND WOUND HEALTH MONITORING FUNCTIONALITIES FOR REAL-TIME MANAGEMENT OF WOUNDS /

By Mir, Mariam . . 265p. , Wound management has been efficiently handled by the development of a smart bi-functional real time modular system that combines and synchronizes quantitative assessment of wound health with wearable drug dispenser for controlled and desired drug dispensation for specific patient demand. The wound monitoring system is composed of a biocompatible, planar, point of care and flexible wearable patch comprising of a pH sensor array that can easily conform to body contours and efficiently provide a spatial map of pH levels for different areas of the wound, since variations in pH are indicative of physiological alteration such as inflammation and tumor growth. The design of pH sensor array is dependent on electrode density, which is a function of both the optimized size and separation of electrodes. Based on the final electrode density, an optimized design of the pH sensor array has been developed, using copper tracts on a polyimide substrate and a hydrophilic pH responsive hydrogel as the pH sensitive component. The treatment module comprising of the wearable drug dispenser has been developed using the concept of an electronically controlled drug delivery through a haptic vibratory mechanism that is precisely controlled and tuned for drug release to affected areas. In addition, an environmentally triggered, pH responsive hydrogel based drug delivery system has also been developed in tandem, as a comparison with the electronically controlled system. The individual components of the proposed wound management system have been extensively tested for physical, chemical and performance related characteristics; subsequently, the systems have been used in the in-vivo setting to establish a baseline for future clinical testing and usability. Our observations and results suggest that the both the diagnostic and treatment components of the wound management system have the potential to mark an improvement in the current situation for wound management in hospital settings. The development of this extensively tested prototype system clears the way for further clinical studies to be undertaken in this regard. 30cm.

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ZnO Based Dental Restorative Materials and Support Membranes to Combat Diabetes Associated Oral Manifestations /

By Tanweer, Tahreem . . 234p. , Diabetes mellitus is a common metabolic disease characterized by sustained hyperglycemia. In diabetic patients, biofouling, microbial oral dysbiosis and chronic inflammation work together to create a powerful trifecta that makes it difficult for dental materials to effectively treat oral complications. This study aims to develop doped zinc oxide based dental restorative materials and support membranes to address diabetes associated oral complications i.e. caries and periodontitis. Silver, copper, and magnesium doped zinc oxide nanoparticles were synthesized via the coprecipitation method and characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, fourier-transform infrared spectroscopy, and X-ray diffraction to assess structural, morphological, and chemical properties. The antibacterial potential of these NPs was tested against Streptococcus mutans using microbial assays. To explore doped Zinc oxide for caries management, zinc oxide and doped zinc oxide nanoparticles (1, 2.5, 5% w/w) were incorporated into commercial resin composite and tested for antibacterial activity against Streptococcus mutans, Enterococcus faecalis, and a normal and diabetic saliva microcosm. Key material properties such as aesthetics, compressive strength, depth of cure, pH response, and hemocompatibility were evaluated. The most promising formulation was tested in diabetic rodent model with secondary caries. For periodontitis management, a synthetic biodegradable support membrane incorporating selected doped zinc oxide was synthesized and characterized using scanning electron microscopy and fourier-transform infrared spectroscopy. Antibacterial efficacy was assessed against Streptococcus mutans, Enterococcus faecalis, and normal and diabetic saliva microcosms. Material properties such as tensile strength, swelling profile, and in vitro degradation were analyzed. The membrane’s bacterial adhesion was evaluated against Fusobacterium nucleatum, a major contributor to biofilm formation in diabetes-related oral conditions. Cell viability of h400 cells was assessed using trypan blue and calcein/propidium iodide assays, while antiinflammatory responses were evaluated by measuring interleukin-8 levels released by h400 cells after exposure to heat-killed F. nucleatum. In vivo testing was conducted on diabetic xi wistar rats with periodontal infection, examining lipid profiles, complete blood count, histology, and radiological findings over 54 days of treatment. Hexagonal silver doped zinc oxide, copper doped zinc oxide, and magnesium doped zinc oxide nanoparticles were prepared. Scanning electron microscopy analysis revealed simple zinc oxide nanoparticles with a uniform size of 23.6 nm, while doped nanoparticles had average sizes of 20.5 nm (silver doped zinc oxide), 39.56 nm (copper doped zinc oxide), and 22.37 ± 2.07 nm (magnesium doped zinc oxide). Antibacterial evaluation against Streptococcus mutans (initial count: 9.68 ± 0.02 log₁₀ CFU/mL) showed reductions to 9.603 ± 0.005 (zinc oxide, p = 0.0056), 9.3 ± 0.009 (silver doped zinc oxide, p < 0.0001), 9.207 ± 0.051 (copper doped zinc oxide, p = 0.002), and 9.43 ± 0.03 (magnesium doped zinc oxide, p = 0.0012) after 6 hours at 10 µg/mL. When incorporated into restorative composites, 2.5% w/w magnesium doped zinc oxide nanoparticles exhibited the best overall performance, showing superior antibacterial efficacy with mean bacterial counts reduced to 5.533 log₁₀ CFU/mL for Streptococcus mutans, 5.200 log₁₀ CFU/mL for Enterococcus faecalis, and 4.533 log₁₀ CFU/mL for diabetic saliva-derived microcosms (p < 0.0001 for all). The 2.5% magnesium doped zinc oxide composite also maintained significantly higher compressive strength (26.18 ± 0.67 MPa) compared to the pristine composite (22.84 ± 0.095 MPa, p < 0.0001), demonstrated stable pH elevation across immersion durations, and preserved acceptable aesthetics despite a statistically significant reduction in depth of cure (p = 0.0002). Furthermore, hemolysis percentages remained within safe limits (<5%), confirming biocompatibility according to ISO/TR 7406 standards. In the secondary caries assessment, 2 out of 3 rats in the pristine group and all 3 rats in the zinc oxide group exhibited carious lesions, whereas 0 out of 3 rats in the magnesium doped zinc oxide group showed any signs of secondary caries. For application in treatment of periodontitis, biodegradable polycaprolactone/sodium alginate/magnesium doped zinc oxide membranes were prepared that exhibited a thickness of approximately 145 ± 20 μm, with a smooth surface and visible aggregates indicating magnesium doped zinc oxide incorporation. Antibacterial testing revealed that xii polycaprolactone/sodium alginate/magnesium doped zinc oxide membrane showed the highest activity against Enterococcus faecalis (8.364 ± 0.05 log₁₀ CFU/mL), Streptococcus mutans (9.13 ± 0.06 log₁₀ CFU/mL), and normal saliva microcosm (7.9 ± 0.17 log₁₀ CFU/mL) compared to polycaprolactone/sodium alginate and polycaprolactone/sodium alginate/silver doped zinc oxide membranes. The ultimate tensile strength was highest in polycaprolactone/sodium alginate/magnesium doped zinc oxide (11.67 ± 0.19 MPa) compared to polycaprolactone/sodium alginate/ zinc oxide (9.94 ± 0.tact angle analysis showed that the addition of magnesium doped zinc oxide reduced the water contact angle to 48.3° ± 0.28, enhancing hydrophilicity compared to polycaprolactone/sodium alginate (55.36° ± 0.924). Moreover, polycaprolactone/sodium alginate/magnesium doped zinc oxide demonstrated an improved swelling capacity (25.1% ± 0.65) after 24 hours of immersion, higher than polycaprolactone/sodium alginate/zinc oxide (23.1% ± 1.37) and polycaprolactone/sodium alginate (17% ± 2.5). After 8 months, degradation analysis revealed the highest degradation in polycaprolactone/sodium alginate/magnesium doped zinc oxide (54.80%), compared to polycaprolactone/sodium alginate/ zinc oxide (44.15%) and polycaprolactone/sodium alginate (37.94%). Hemolysis assays confirmed the biocompatibility of all membranes, with hemolysis rates of 4.8 ± 0.11% for polycaprolactone/sodium alginate, 4.5 ± 0.25% for polycaprolactone/sodium alginate/silver doped zinc oxide, and 4.1 ± 0.21% for polycaprolactone/sodium alginate/magnesium doped zinc oxide, all remaining below the 5% safety limit. The study on diabetic wistar rat showed elevated triglyceride and low density lipopolysachride levels in the diabetic + periodontitis group, reflecting a dysregulated lipid profile associated with systemic inflammation. Treatment with the polycaprolactone/sodium alginate/magnesium doped zinc oxide membrane resulted in a statistically significant reduction in total cholesterol, triglycerides, and LDL levels. This improvement in lipid parameters was accompanied by a marked decrease in periodontal infection and inflammation. Radiological evaluations also showed visible signs of regeneration in treated rats. xiii The Fusobacterium nucleatum adhesion values varied significantly across the membranes, with polycaprolactone/sodium alginate showing a mean adhesion of 9.38% ± 5.18, while polycaprolactone/sodium alginate/magnesium doped zinc oxide exhibited the lowest mean adhesion of 0.7% ± 0.6. Cell viability testing showed untreated cells had 89.45% ± 2.051 viability, with polycaprolactone/sodium alginate, and polycaprolactone/sodium alginate/magnesium doped zinc oxide membranes resulting in 69.15%, 75.67%, and 76.90% viability, respectively. After 18 h of incubation, the control group having cells treated with health killed Fusobacterium nucleatum indicated a significant enhancement in CXCL8 levels (537 + 356 ng/mL). Both PCL/SA/ZnO and PCL/SA/MgZnO membranes were found to eliminate the release of CXCL8 in H400 cells following the same 18-hour exposure period.This study concludes that magnesium doped zinc oxide-based dental materials offer promising antibacterial and anti-inflammatory properties, along with enhanced mechanical strength, to address the oral health challenges associated with diabetes. In the future, these materials hold great potential for advancing dental care in high-risk populations such as diabetic patients. 30cm.

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MULTIFUNCTIONAL WOUND HEALING DEVICE WITH CONTROLLED DRUG DELIVERY AND WOUND HEALTH MONITORING FUNCTIONALITIES FOR REAL-TIME MANAGEMENT OF WOUNDS /

ZnO Based Dental Restorative Materials and Support Membranes to Combat Diabetes Associated Oral Manifestations /