Cu-MOF loaded chitosan based freeze-dried highly porous dressings with anti-biofilm and pro-angiogenic activities accelerated Pseudomonas aeruginosa infected wounds healing in rats.

Metal-organic frameworks (MOFs)-based therapy opens a new area for antibiotic-drug free infections treatment. In the present study, chitosan membranes (CS) loaded with two concentrations of copper-MOF 10 mg/20 ml (Cu-MOF10/CS) & 20 mg/20 ml (Cu-MOF20/CS) were prepared by a simple lyophilization procedure. FTIR spectra of Cu-MOF10/CS and Cu-MOF20/CS dressings confirmed absence of any undesirable chemical changes after loading Cu-MOF. The SEM images of the synthesized materials (CS, Cu-MOF10/CS & Cu-MOF20/CS) showed interconnected porous structures. Cytocompatibility of the materials was confirmed by fibroblasts cells culturing and the materials were hemocompatible, with blood clotting index <5 %. Cu-MOF20/CS showed comparatively higher effective antibacterial activity against the tested strains; E. coli (149.2 %), P. aeruginosa (165 %) S. aureus (117.8 %) and MRSA (142 %) as compared to Amikacin, CS and Cu-MOF10/CS membranes. Similarly, Cu-MOF20/CS dressing significantly eradicated the biofilms; P. aeruginosa (37 %) and MRSA (52 %) respectively. In full thickness infected wound rat model, on day 23, Cu-MOF10/CS and Cu-MOF20/CS promoted wound healing up to 87.7 % and 82 % respectively. H&E staining of wounded tissues treated with Cu-MOF10/CS & Cu-MOF20/CS demonstrated enhanced neovascularization and re-epithelization along-with reduced inflammation, while trichrome staining exhibited increased collagen deposition. Overall, this study declares Cu-MOFs loaded chitosan dressings a multifunctional platform for the healing of infected wounds.

Generation of Pearl/Calcium Phosphate Composite Particles and Their Integration into Porous Chitosan Scaffolds for Bone Regeneration.

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

Bacterial Inhibition and Osteogenic Potentials of Sr/Zn Co-Doped Nano-Hydroxyapatite-PLGA Composite Scaffold for Bone Tissue Engineering Applications.

Bacterial infection associated with bone grafts is one of the major challenges that can lead to implant failure. Treatment of these infections is a costly endeavor; therefore, an ideal bone scaffold should merge both biocompatibility and antibacterial activity. Antibiotic-impregnated scaffolds may prevent bacterial colonization but exacerbate the global antibiotic resistance problem. Recent approaches combined scaffolds with metal ions that have antimicrobial properties. In our study, a unique strontium/zinc (Sr/Zn) co-doped nanohydroxyapatite (nHAp) and Poly (lactic-co-glycolic acid) -(PLGA) composite scaffold was fabricated using a chemical precipitation method with different ratios of Sr/Zn ions (1%, 2.5%, and 4%). The scaffolds' antibacterial activity against Staphylococcus aureus were evaluated by counting bacterial colony-forming unit (CFU) numbers after direct contact with the scaffolds. The results showed a dose-dependent reduction in CFU numbers as the Zn concentration increased, with 4% Zn showing the best antibacterial properties of all the Zn-containing scaffolds. PLGA incorporation in Sr/Zn-nHAp did not affect the Zn antibacterial activity and the 4% Sr/Zn-nHAp-PLGA scaffold showed a 99.7% bacterial growth inhibition. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay showed that Sr/Zn co-doping supported osteoblast cell proliferation with no apparent cytotoxicity and the highest doping percentage in the 4% Sr/Zn-nHAp-PLGA was found to be ideal for cell growth. In conclusion, these findings demonstrate the potential for a 4% Sr/Zn-nHAp-PLGA scaffold with enhanced antibacterial activity and cytocompatibility as a suitable candidate for bone regeneration.

A study of the comparative effect of cerium oxide and cerium peroxide on stimulation of angiogenesis: Design and synthesis of pro-angiogenic chitosan/collagen hydrogels.

Poor angiogenesis at injury site is a major problem in chronic wounds, which could lead to limbs amputation in adverse cases. To overcome this issue, several efforts have made in literature and by our group as well to develop pro-angiogenic agents. For this purpose, metal oxides due to their oxidative potential have been studied and found very attractive agents. Cerium oxides are proven to be non-toxic and their biological studies have already proved their importance in preventing chronic inflammation, and neurological diseases among several others by modulating the intracellular reactive oxygen species. In current study, we report the synthesis and neovascularization activity of cerium oxide and cerium peroxide nanoparticles when loaded into chitosan and collagen hydrogel. The hydrogels were characterized by FTIR, SEM and XRD. The pro-angiogenic behavior of these hydrogels was studied by in-vivo CAM assay. It was found that cerium peroxide loaded material showed significantly increase in angiogenesis as compared to cerium oxide loaded materials. It was demonstrated that cerium peroxide hydrogels enhanced the angiogenic capability in CAM assay as compared to cerium oxide and hence holds good potential for chronic ulcer and burn wounds healing.

Potential of electrospun chitosan fibers as a surface layer in functionally graded GTR membrane for periodontal regeneration.

OBJECTIVE: The regeneration of periodontal tissues lost as a consequence of destructive periodontal disease remains a challenge for clinicians. Guided tissue regeneration (GTR) has emerged as the most widely practiced regenerative procedure. Aim of this study was to electrospin chitosan (CH) membranes with a low or high degree of fiber orientation and examines their suitability for use as a surface layer in GTR membranes, which can ease integration with the periodontal tissue by controlling the direction of cell growth. METHODS: A solution of CH-doped with polyethylene oxide (PEO) (ratio 95:5) was prepared for electrospinning. Characterization was performed for biophysiochemical and mechanical properties by means of scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, swelling ratio, tensile testing and monitoring degradation using pH analysis, weight profile, ultraviolet-visible (UV-vis) spectroscopy and FTIR analysis. Obtained fibers were also assessed for viability and matrix deposition using human osteosarcoma (MG63) and human embryonic stem cell-derived mesenchymal progenitor (hES-MP) cells. RESULTS: Random and aligned CH fibers were obtained. FTIR analysis showed neat CH spectral profile before and after electrospinning. Electropsun mats were conducive to cellular attachment and viability increased with time. The fibers supported matrix deposition by hES-MPs. Histological sections showed cellular infiltration as well. SIGNIFICANCE: The surface layer would act as seal to prevent junctional epithelium from falling into the defect site and hence maintain space for bone regeneration.

Effect of calcium hydroxide on mechanical strength and biological properties of bioactive glass.

In this manuscript for the first time calcium hydroxide (Ca(OH)2) has been used for preparation of bioactive glass (BG-2) by co-precipitation method and compared with glass prepared using calcium nitrate tetrahydrate Ca(NO3)2·4H2O (BG-1), which is a conventional source of calcium. The new source positively affected physical, biological and mechanical properties of BG-2. The glasses were characterized by Fourier transform infrared (FTIR), X-Ray Diffractometer (XRD), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA-DSC), BET surface area analysis and Knoop hardness. The results showed that BG-2 possessed relatively larger surface properties (100m(2)g(-1) surface area) as compared to BG-1 (78m(2)g(-1)), spherical morphology and crystalline phases (wollastonite and apatite) after sintering at lower than conventional temperature. These properties contribute critical role in both mechanical and biological properties of glasses. The Knoop hardness measurements revealed that BG-2 possessed much better hardness (0.43±0.06GPa at 680°C and 2.16±0.46GPa at 980°C) than BG-1 (0.24±0.01 at 680°C and 0.57±0.07GPA at 980°C) under same conditions. Alamar blue Assay and confocal microscopy revealed that BG-2 exhibited better attachment and proliferation of MG63 cells. Based on the improved biological properties of BG-2 as a consequent of novel calcium source selection, BG-2 is proposed as a bioactive ceramic for hard tissue repair and regeneration applications.

Dental materials for cleft palate repair.

Numerous bone and soft tissue grafting techniques are followed to repair cleft of lip and palate (CLP) defects. In addition to the gold standard surgical interventions involving the use of autogenous grafts, various allogenic and xenogenic graft materials are available for bone regeneration. In an attempt to discover minimally invasive and cost effective treatments for cleft repair, an exceptional growth in synthetic biomedical graft materials have occurred. This study gives an overview of the use of dental materials to repair cleft of lip and palate (CLP). The eligibility criteria for this review were case studies, clinical trials and retrospective studies on the use of various types of dental materials in surgical repair of cleft palate defects. Any data available on the surgical interventions to repair alveolar or palatal cleft, with natural or synthetic graft materials was included in this review. Those datasets with long term clinical follow-up results were referred to as particularly relevant. The results provide encouraging evidence in favor of dental and other related biomedical materials to fill the gaps in clefts of lip and palate. The review presents the various bones and soft tissue replacement strategies currently used, tested or explored for the repair of cleft defects. There was little available data on the use of synthetic materials in cleft repair which was a limitation of this study. In conclusion although clinical trials on the use of synthetic materials are currently underway the uses of autologous implants are the preferred treatment methods to date.

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration.

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration.

An update on glass fiber dental restorative composites: a systematic review.

Dentistry is a much developed field in the last few decades. New techniques have changed the conventional treatment methods as applications of new dental materials give better outcomes. The current century has suddenly forced on dentistry, a new paradigm regarding expected standards for state-of-the-art patient care. Within the field of restorative dentistry, the incredible advances in dental materials research have led to the current availability of esthetic adhesive restorations. The chemistry and structure of the resins and the nature of the glass fiber reinforced systems in dental composites are reviewed in relation to their influence and properties including mechanical, physical, thermal, biocompatibility, technique sensitivity, mode and rate of failure of restorations on clinical application. It is clear that a deeper understanding of the structure of the polymeric matrix and resin-based dental composite is required. As a result of ongoing research in the area of glass fiber reinforced composites and with the development and advancement of these composites, the future prospects of resin-based composite are encouraging.

Effect of pH, polymer concentration and molecular weight on the physical state properties of tolfenamic acid.

Tolfenamic acid (TA) has been transformed from crystalline to amorphous state through freeze-drying by using varying ratios of polyacrylic acid (PA) at various pH values. The characterization of the films has been carried out using X-ray diffraction, differential scanning calorimetry, Fourier transform infrared (FTIR) spectrometry and scanning electron microscopy. The results showed a gradual change in the solid state properties of TA and a complete transformation into its amorphous form in 1:8, 1:4, 1:2 and 1:1 ratios at pH 3, 4, 5 and 6, respectively. FTIR spectrometry reveals the formation of a yellow polymorphic form of TA. Polymer molecular weight has also been observed to affect the drug transformation and interaction as the low molecular weight PA (Mw ∼ 1800) was found to be most effective followed by its medium (Mv ∼ 450 000) and high molecular weight (Mv ∼ 3 000 000) forms. No signs of recrystallization in the TA-PA films were noted during the 12-week storage period. PA of low molecular weight has also been found more effective in inhibiting the recrystallization of the melt upon cooling thus proving a valuable polymer in producing stable amorphous solid dispersions of TA.

Preparation and characterization of bioactive composites and fibers for dental applications.

OBJECTIVES: The present study was carried out to create composites and fibers using polyurethane (PU) with hydroxyapatite (HA) that could be used for dental applications. METHODS: Composites with varying HA concentration were prepared by solution casting technique. Similarly, PU-HA fibers with varying PU hard and soft segments and fixed HA concentration were also prepared. Various characterization techniques, such as, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy and Fourier transform infrared spectroscopy in conjunction with photo-acoustic sampling cell were employed to study the composites and fibers for changes in their physicochemical properties before and after immersion in artificial saliva at 37°C for up to 5 days. RESULTS: The results indicated formation of amorphous apatite layers with maximum amorphicity in composites containing highest amount of HA with 5 days of immersion in artificial saliva. Similarly, fibers with more PU hard segment resulted in better transformation of crystalline HA to its amorphous state with increasing immersion time thus confirming the bioactive nature of the HA-PU fibers. SIGNIFICANCE: Concentrations of HA and PU hard segment along with the duration of immersion in artificial saliva are two major factors involved in the modification of solid-state properties of HA. The amorphous apatite layer on the surface is known to have tendency to bind with living tissues and hence the use of optimum amount of HA and PU hard segment in composites and fibers, respectively could help in the development of novel dental filling material.

Synthesis and characterizations of a fluoride-releasing dental restorative material.

The aim was to develop an obturating material which has the tendency to release fluoride and minimize interfaces with tooth. Nano-fluorapatite (nFA) powder was synthesized by sol-gel. The composite based on polyurethane (PU) was obtained by chemically binding the nFA (10, 15, 20%wt/wt) to the diisocyanate component by utilizing in-situ polymerization. The procedure involved stepwise addition of monomeric units of PU, and optimizing the reagent concentrations to synthesize composite. The structural, phase and morphological analysis of nFA was evaluated. The structural, fluoride release and in-vitro adhesion analysis with tooth structure of PU/nFA was conducted. For fluoride release analysis the samples were stored in artificial saliva and deionized water for periodical time intervals. Bond strength of composites was analyzed by push-out test. Chemical linkage was achieved between PU and nFA without intermediate coupling agent. The insignificant difference of fluoride release pattern was observed in artificial saliva and (p≥0.05) deionized water. The PU/nFA composite provided sustained release of fluoride over a long period of time. The composite showed more adhesion toward tooth structure with the increase in concentration of nFA. Bond strength of composite was in accordance with root canal filling material, hence, the material with anti-cariogenic properties can be used as an obturating material.

High-strength nanograined and translucent hydroxyapatite monoliths via continuous hydrothermal synthesis and optimized spark plasma sintering.

The synthesis of high-strength, completely dense nanograined hydroxyapatite (bioceramic) monoliths is a challenge as high temperatures or long sintering times are often required. In this study, nanorods of hydroxyapatite (HA) and calcium-deficient HA (made using a novel continuous hydrothermal flow synthesis method) were consolidated using spark plasma sintering (SPS) up to full theoretical density in ∼5 min at temperatures up to 1000°C. After significant optimization of the SPS heating and loading cycles, fully dense HA discs were obtained which were translucent, suggesting very high densities. Significantly high three-point flexural strength values for such materials (up to 158 MPa) were measured. Freeze-fracturing of disks followed by scanning electron microscopy investigation revealed selected samples possessed sub-200 nm sized grains and no visible pores, suggesting they were fully dense.