Synthesis, Characterisation and 3D Printing of an Isosorbide Based, Light Curable, Degradable Polymer for Potential Application in Maxillofacial Reconstruction

Although emergence of bone tissue engineering techniques has revolutionised the field of maxillofacial reconstruction, the successful translation of such products, especially concerning larger sized defects, still remains a significant challenge. Light curable methacrylate based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to synthesise a mechanically stable and biologically functional polymer for reconstruction of complex craniofacial defects. The experimental work initially involved synthesis of (((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1-diyl) bis((4-methyl-3-oxopent-4-en-1-yl)carbamate), CSMA-1, and ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5-trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate), CSMA-2; Nuclear Magnetic Resonance (NMR) analysis confirmed formation of the monomers and composite samples were fabricated respectively by exposing 11 mm diameter discs to blue light. Modulus of the tensile elasticity was tested using a biaxial flexural test and the values were found to be between 1 and 3 GPa in CMA-1, CSMA-2 and their composites. In vitro cell culture, using human Bone Marrow Derived Mesenchymal Stem Cells (BMSCs), confirmed non-toxicity of the samples and finally 3D printing allowed direct extrusion and setting of the bio ink into a mesh-like construct

Pyogenic granuloma as a presenting sign of hydroxyapatite orbital implant exposure: A clinicopathologic study

PURPOSE: We report 5 unusual cases of exposed hydroxyapatite orbital implants that presented as pyogenic granulomas. We propose pathogenesis and histopathologic correlations. METHODS: A clinicopathologic study of 5 patients with hydroxyapatite implants who presented with pyogenic granuloma. RESULTS: Pyogenic granulomas were detected 1.5 to 30 months after implantation in 5 patients. The lesions were multiple but were not related to the wound margin at the exposed area and were not covered by the surface epithelium in most instances. Exposure defects were detected in all patients at the time of lesion excision. The mean exposure size in the greatest dimension was 16 mm (range, 9-20 mm). Three patients were treated successfully with simple excision of the granulomas, burring down of the anterior surface of the implants, and direct repair of the exposure defects. Explantation of the implant was performed in 2 cases. Histopathologic examination revealed chronic inflammation and microabscess formation in the explanted implants. CONCLUSIONS: Five patients with pyogenic granulomas were found to have hydroxyapatite exposure. Pyogenic granuloma should not be considered a benign lesion on a hydroxyapatite orbital implant, especially in recurrent cases. Ophthalmologists must be aware of the possibility of conjunctival dehiscence with hydroxyapatite-implant exposure beneath the lesion. ©2006The American Society of Opthalmic Plastic and Reconstructive Surgery, Inc

Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats

Purpose: Acute kidney injury (AKI) induces acute lung injury (ALI) through releasing injurious mediators or impairing clearance of systemic factors. To determine the links between AKI and ALI, pulmonary and blood variables were evaluated following induction of AKI via different experimental models of bilateral renal ischemia/reperfusion (BIR: renal ischemia with uremia), unilateral renal ischemia/reperfusion (UIR: renal ischemia without uremia), bilateral nephrectomy (BNX: uremia without renal ischemia), and unilateral nephrectomy (UNX: without uremia and renal ischemia). Methods: Ninety male Sprague–Dawley rats were divided into six groups. Animals had 1-h bilateral or 2-h unilateral renal ischemia followed by 24-h reperfusion in the BIR and UIR groups, respectively, and 24-h period following bilateral or unilateral nephrectomy in the BNX and UNX groups, respectively. There were also sham and control groups with and without sham-operation, respectively. Results: Plasma malondialdehyde and nitric oxide were elevated by BIR more than UIR, but not changed by UNX and BNX. UIR slightly increased plasma creatinine, whereas BIR and BNX largely increased plasma creatinine, urea, K+and osmolality and decreased arterial HCO3 −, pH, and CO2. UNX and UIR did not affect lung, but BIR and BNX induced ALI with equal capillary leak and macrophages infiltration. However, there were more prominent lung edema and vascular congestion following BNX and more severe neutrophils infiltration and PaO2/FiO2 reduction following BIR. Conclusion: Acutely accumulated systemic mediators following renal failure in the absence of kidneys vary from those due to combined renal failure with ischemic-reperfused kidneys and consequently they induce ALI with distinct characteristics

Clinical features of graves' ophthalmopathy and impact of enalapril on the course of mild graves’ ophthalmopathy: A pilot study

Background: Inflammation, oxidative stress, and adipogenesis are associated with Graves’ ophthalmopathy (GO) progression. Objective: We conducted a pilot study to investigate the effect of Enalapril on patients with mild ophthalmopathy. Method: Based on the comprehensive eye examination, 12 patients with mild ophthalmopathy were selected from referred Graves’ patients and treated with Enalapril (5 mg daily) for 6 months. Clinical and ophthalmological examination [IOP (Intraocular Pressure), vision, Margin reflex distance and exophthalmia measurement, CAS (clinical activity score) and VISA [V (vision); I (inflamma-tion/congestion); S (strabismus/motility restriction); and A (appearance/exposure] score assessment) was performed at the beginning, 3 months and 6 months of the study period. Quality of life was also evaluated using a standard questionnaire. Results: Mean exophthalmia at the first visit was 18.75 ± 2.39, 3 months later 18.53 ± 2.39 and 6 months later was 17.92 ± 2.31, respectively. Mean CAS was 0.71 ± 0.82 (first visit), 0.57 ± 0.54 (3 months) and 0.14 ± 0.36 (6 months), respectively. Mean Margin reflex distance was 9.09 ± 4.36 (first visit) and 9.60 ± 4.40 (6 months), respectively. There were significant differences in the case of exophthalmia (P=0.002), CAS (P=0.006), and Margin reflex distance (P=0.029) between the first visit and 6 months after treatment. The difference between the score of quality of life in patients with GO after 6 months of follow up was statistically significant (P = 0.006). Conclusion: Our results showed that Enalapril treatment could ameliorate the clinical course of GO according to the ophthalmologic examinations and subjective parameters of disease progression. However, further studies should be performed to determine the efficacy of Enalapril in Graves’ ophthalmopathy treatment

The Effect of Bright Light on Physiological Circadian Rhythms and Subjective Alertness of Shift Work Nurses in Iran

In this study, the effects of bright light (BL) on the rhythms in body temperature, plasma melatonin, plasma cortisol and subjective alertness, in 34 shift work nurses at a university hospital were assessed. They were exposed to very BL (4 500 lx) during 2 breaks (21:15–22:00 and 3:15–4:00) or dim light (300 lx). The subjects were studied under 24 h of realistic conditions during which their plasma cortisol and melatonin were measured at 3-h intervals; their body temperature was also measured during and after night shift work. Subjective alertness was evaluated with the Karolinska sleepiness scale. Administration of BL significantly suppressed night-time melatonin levels. A one-way ANOVA revealed that BL tended to increase cortisol levels and body temperature and significantly improved alertness. These results demonstrate that photic stimulation in a hospital setting can have a powerful influence on the adjustment of the circadian system

Mussel Inspired Chemistry and Bacteria Derived Polymers for Oral Mucosal Adhesion and Drug Delivery

Ulceration of the oral mucosa is common, can arise at any age and as a consequence of the pain lessens enjoyment and quality of life. Current treatment options often involve the use of topical corticosteroids with poor drug delivery systems and inadequate contact time. In order to achieve local controlled delivery to the lesion with optimal adhesion, we utilized a simple polydopamine chemistry technique inspired by mussels to replicate their adhesive functionality. This was coupled with production of a group of naturally produced polymers, known as polyhydroxyalkanoates (PHA) as the delivery system. Initial work focused on the synthesis of PHA using Pseudomonas mendocina CH50; once synthesized and extracted from the bacteria, the PHAs were solvent processed into films. Polydopamine coating was subsequently achieved by immersing the solvent cast film in a polymerized dopamine solution. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy confirmed functionalization of the PHA films via the presence of amine groups. Further characterization of the samples was carried out via surface energy measurements and Scanning Electron Microscopy (SEM) micrographs for surface topography. An adhesion test via reverse compression testing directly assessed adhesive properties and revealed an increase in polydopamine coated samples. To further identify the effect of surface coating, LIVE/DEAD imaging and Alamar Blue metabolic activity evaluated attachment and proliferation of fibroblasts on the biofilm surfaces, with higher cell growth in favor of the coated samples. Finally, in vivo biocompatibility was investigated in a rat model where the polydopamine coated PHA showed less inflammatory response over time compared to uncoated samples with sign of neovascularization. In conclusion, this simple mussel inspired polydopamine chemistry introduces a step change in bio-surface functionalization and holds great promise for the treatment of oral conditions

Comparative study of photoinitiators for the synthesis and 3D printing of a light-curable, degradable polymer for custom- fit hard tissue implants

Three-dimensional (3D) printing enhances the production of on-demand fabrication of patient-specific devices as well as anatomically fitting implants with high complexity in a cost-effective manner. Additive systems that employ vat photopolymerisation such as stereolithography (SLA) and digital light projection (DLP) are used widely in the field of biomedical science and engineering. However, additive manufacturing methods can be limited by the types of materials that can be used. In this study, we present an isosorbide-based formulation for a polymer resin yielding a range of elastic moduli between 1.73 GN/mm2 dependent on the photoinitiator system used as well as the amount of calcium phosphate filler added. The monomer was prepared and enhanced for 3D-printing using an SLA technique that delivered stable and optimized 3D-printed models. The resin discussed could potentially be used following major surgery for the correction of congenital defects, the removal of oral tumours and the reconstruction of the head and neck region. The surgeon is usually limited with devices available to restore both function and appearance and with the ever-increasing demand for low-priced and efficient facial implants, there is an urgent need to advance new manufacturing approaches and implants with a higher osseointegration performance