scholarly journals Transglutaminase Cross-Linked Gelatin-Alginate-Antibacterial Hydrogel as the Drug Delivery-Coatings for Implant-Related Infections

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 414
Author(s):  
Chung-Kai Sun ◽  
Cherng-Jyh Ke ◽  
Yi-Wen Lin ◽  
Feng-Huei Lin ◽  
Tung-Hu Tsai ◽  
...  

Implant-related infection may be catastrophic and result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Based on a transglutaminase (TGase) cross-linked/antibiotics-encapsulated gelatin-alginate hydrogel, the main aim of this study is to establish an effective antibiotic slow-release system. The second aim is to evaluate the efficacy of a hydrogel-encapsulated antibiotic-containing titanium pin in preventing implant-related infections in a rat model. The prepared gelatin/alginate/gentamicin or vancomycin hydrogel was covalently cross-linked with transglutaminase (TGase). Its drug release profile and cytotoxicity were determined and the Wistar rat animal model was performed to validate its efficacy by radiographic examination, Micro-CT (computed tomography) evaluation and histo-morphological analysis at 12 weeks after surgery. When gelatin and alginate were thoroughly mixed with TGase, both 0.5% and 1.0% TGase can effectively cross link the hydrogel; the release of antibiotic is slowed down with higher degree of TGase concentration (from 20 min to more than 120 h). In the animal study, antibiotic-impregnated hydrogel is effective in alleviating the implant-related infections. Relative to that of a positive control group, the experimental group (vancomycin treatment group) showed significant higher bone volume, more intact bony structure with only mild inflammatory cell infiltration. This newly designed hydrogel can effectively deliver antibiotics to reduce bacterial colonization and biofilm formation on the implant surface. The remaining challenges will be to confer different potent antibacterial medications with good biocompatibility and fulfill the safety, practical and economic criteria for future clinical translation.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S773-S775
Author(s):  
Alexander A Ozoria Loveras ◽  
Jacques Paré Espinal ◽  
David de luna ◽  
Noemi Acevedo

Abstract Background In 2018, a review of the scientific literature identifed biofilm studies in the past 3 years. Wherein, the role of the biofilm in the progression of the diabetic foot ulcer with the presence of biofilm is reviewed. As a result, tissue sampling is more effective than transcure, Levin, and aspiration. A study in Cuba evaluate the effectiveness of a new proposal for antimicrobial treatment in patients with diabetic foot infection in 2017. The method used was a experimental type of two groups. The control group, was treated with the treatment scheme proposed in the Comprehensive Care Program for the patient with diabetic foot ulcer (PAIPUPD). Instead, the other experimental group was treated according to the scheme based on the local microbial map. They used a random distribution. Using the Wagner classification, there were patients classificate with a grade of W2 (13% of patients), W3 (66%) and W4 (12%). The most frequent germs found were Staphylococcus aureus, Escherichia coli and Enterobacter sp. The experimental group required less days with hospitalization. Methods This is an observational study of primary source with a non-probability sample with 58 patients. Adult patients diagnosed with type 2 diabetes mellitus, with diabetic foot, Wagner classification 1, 2 and 3, who attended the healing area of the Institute of Diabetes of Santiago were included. After identifying the colonized pathogen, its cicatrization process was evaluate for four weeks. Results Of the total sample, 12.07% belonged to Wagner 1, 43.1% to Wagner 2 and 44.83% to the Wagner 3 classification. In the case of the Wagner 3 group, S. aureus and Pseudomona aeruginosa were present in 6 cases. Despite the infectious processes detected by the culture, the patients showed a successful cicatrization process after four weeks of evaluation. Graph 1: Isolated Microorganism Vs Wagner’s Degree (n=60) Graph 2: Gram positive microorganism vs. healing process per week in patients with diabetic foot (n=22) Graph 3: Gram-negative microorganism vs. healing process (n=33) Conclusion During the four weeks of clinical evaluation, more than 88% of patients progressed positively to clinical recovery, regardless of the type of bacteria colonized and/or their resistance to antibiotics. Disclosures All Authors: No reported disclosures


2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.


2021 ◽  
Vol 13 (9) ◽  
pp. 1716-1723
Author(s):  
Jie Li ◽  
Chao Xu ◽  
Yueyue Lu ◽  
Yan Zhang ◽  
Xiaoping Tan

Nanoparticles are known to have recognition ability for targeted delivery, and are thus widely used in the treatments of diseases. Mesoporous nano-titanium dioxide (TiO2) nanoparticles have characteristics of nanomaterials and their porous structure with high surface area strengthens their drug-loading capacity and targeting ability. This study aimed to investigate the effect of mesoporous nano-TiO2 on pancreatic cancer cells and STAT pathway activity. Initially, we prepared mesoporous TiO2 nanoparticles that were characterized. Pancreatic cancer cells were co-cultured with mesoporous nano-TiO2 nanoparticles at different concentrations (0.1 μg/mL, 0.5 μg/mL, 1 μg/mL, 5 μg/mL, and 10 μg/mL) or 10 μg/mL nano-TiO2 (positive control group) or cells cultured alone (blank group). Cell viability was determined at several specific time points (24 h, 48 h, and 72 h). Transwell assay and scratching assay were conducted to determine the number of migrated and invaded cells. STAT3 and JAK2 expressions were examined by RT-qPCR and Western blot analysis. The prepared mesoporous nano-TiO2 exhibited sharp diffraction peaks with enhanced intensity and diffraction rings. STAT pathway was activated in pancreas cancer cells, which had more fluorescent cells than normal cells. The presence of mesoporous nano-TiO2 nanoparticles suppressed cancer cell viability and their inhibition rate increased with increased of nano-TiO2 concentration. The concentration of 10 μg/mL exhibited greatest inhibitory effect and 10 μg/mL mesoporous nano-TiO2 thus was chosen for experimental group. The width of the scratch in the experimental group (19.97±0.82 mm) was higher than in the blank group and positive control group (P < 0.05); 10 μg/mL mesoporous nano-TiO2 significantly decreased the number of invaded cells (71.97±17.84) and number of cell clones (156.91±31.03) (P < 0.05). The expression levels of STAT3 (0.41±0.06 μg/μL) and JAK2 (0.39±0.04 ug/ul) were diminished by treatment with mesoporous nano-TiO2. Mesoporous nano-TiO2 inhibits pancreatic cancer cell growth and STAT expression, as its inhibitory effect depends on its concentration. These findings might provide a novel insight into nanoparticle-based treatment for pancreatic cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Carolina Ferrairo Danieletto-Zanna ◽  
Vinícius Ferreira Bizelli ◽  
Guilherme André Del Arco Ramires ◽  
Tamires Melo Francatti ◽  
Paulo Sérgio Perri de Carvalho ◽  
...  

Membranes that aid the guided bone regeneration (GBR) process have been the subject of studies of compatible biomaterials that contribute to this repair process. The present study compared different membranes used in critical-size defects of rat calvaria by assessing GBR as well as histological, histomorphometric, and immunohistochemical reactions. Forty-eight male albino Wistar rats were randomly allocated into four groups (n = 12 each), namely, C: membrane-free control group (only blood clot, negative control group); BG: porcine collagen membrane group (Bio-Gide®, positive control group); GD: bovine cortical membrane group (first experimental group); and GDF: thicker bovine cortical membrane group (second experimental group). Rats were euthanized at 30 and 60 days postoperatively. Quantitative data from the histometric analysis were submitted to two-way ANOVA and Tukey’s posttest when p<0.05. Histomorphometric results of the thicker bovine cortical membrane at 30 and 60 days were promising, showing improved new bone formation values (p<0.05), and the CD group presented similar results in both analysis periods, being surpassed only by the GDF group (p<0.05). The immunohistochemical results were associated with the histomorphometric data. A less-thick membrane also assisted in GBR. All membranes promoted GBR, especially the positive control and experimental groups.


2017 ◽  
Vol 45 (4) ◽  
pp. 1324-1331 ◽  
Author(s):  
Lu-yong Jiang ◽  
Xiao Yu ◽  
Qing-jiang Pang

Objective To elucidate the effects of recombinant human erythropoietin (rHuEPO) on steroid-induced osteonecrosis of the femoral head in rats. Methods Twenty-four adult Wistar rats were randomly divided into three groups of eight rats each. The rats in the positive control group were injected with dexamethasone at 1 mg/kg twice a week for 5 weeks. The rats in the negative control group were injected with sodium chloride alone. The rats in the experimental group were injected with dexamethasone at 1 mg/kg twice a week for 5 weeks and rHuEPO (500 u/d/kg) daily for 5 weeks. The femoral head on one side was examined by hematoxylin and eosin staining, and that on the other side was examined by CD31 staining of the capillaries. Results Hematoxylin and eosin staining in the positive control group showed that the bony trabeculae had become obviously narrow and sparse with discontinuity of the integrity. The integrity of the trabeculae was better in the experimental group than positive control group. The CD31 expression was lower in the positive control group than in the other two groups. Conclusion rHuEPO can effectively prevent osteocyte apoptosis, delaying or decreasing osteonecrosis of the femoral head.


2013 ◽  
Vol 83 (5) ◽  
pp. 774-781 ◽  
Author(s):  
Ayad Alsagheer ◽  
Loren W. Kline ◽  
Michael R. Doschak ◽  
Paul W. Major

ABSTRACT Objectives: To establish a rat model of a one-piece mandible using the principles of gingivoperiosteoplasty and guided bone regeneration to fuse the midline symphyseal area. Material and Methods: Twenty-four Sprague-Dawley female rats were divided into two groups: 12 experimental and 12 control. Both groups were imaged using in vivo micro-computed tomography at baseline and at end point (5 months). The experimental group received regenerative surgery at the symphysis area; the control group received no treatment. Outcomes were evaluated by radiographic examination of gross and volumetric bony changes in the symphyseal region of interest marked between the mental foramina bilaterally and the two central incisors near the most coronal margin of the alveolar crests. These landmarks were chosen as they can be reproduced on the computed tomography images at baseline and end point. Histologic examination was performed on all samples at a level 5 mm apical to the alveolar bone crest. Results: Radiologic and histologic examinations of the experimental group revealed complete bony fusion of the symphyseal area in three subjects, partial fusion in five subjects, and thickening of the alveolar bony socket in three subjects; one rat died of anesthesia-related complications. No evidence of fusion or alveolar bone thickening was found in any of the controls. Conclusions: This surgical animal model demonstrates that a rat mandible can be surgically manipulated to mimic the one-piece human mandible. This novel model may prove useful in studying mandibular bone remodeling and orthodontic mandibular tooth movement.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fernando P. S. Guastaldi ◽  
Daniel Yoo ◽  
Charles Marin ◽  
Ryo Jimbo ◽  
Nick Tovar ◽  
...  

The surface energy of the implant surface has an impact on osseointegration. In this study, 2 surfaces: nonwashed resorbable blasting media (NWRBM; control) and Ar-based nonthermal plasma 30 days (Plasma 30 days; experimental), were investigated with a focus on the surface energy. The surface energy was characterized by the Owens-Wendt-Rabel-Kaelble method and the chemistry by X-ray photoelectron spectroscopy (XPS). Five adult beagle dogs received 8 implants (n=2per surface, per tibia). After 2 weeks, the animals were euthanized, and half of the implants (n=20) were removal torqued and the other half were histologically processed (n=20). The bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated on the histologic sections. The XPS analysis showed peaks of C, Ca, O, and P for the control and experimental surfaces. While no significant difference was observed for BIC parameter (P>0.75), a higher level for torque (P<0.02) and BAFO parameter (P<0.01) was observed for the experimental group. The surface elemental chemistry was modified by the plasma and lasted for 30 days after treatment resulting in improved biomechanical fixation and bone formation at 2 weeks compared to the control group.


2004 ◽  
Vol 27 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Paulo Floriani Kramer ◽  
Ítalo Medeiros Faraco Júnior ◽  
Raquel Meira

The purpose of this study was to determine the prevalence and anatomic characteristics of accessory foramina in the external and internal furcation areas of primary molars. Sixty human primary molars were divided into two equal groups. The teeth of the experimental group showed in previous radiographic examination the presence of a radiolucency area confined to the inter-radicular region, while the teeth of the control group had no sign of pulpal inflammation in the clinical and/or radiographic examination. The specimens were observed by scanning electron microscope (SEM). The external furcation area (EFA) showed a higher prevalence of accessory foramina than the internal furcation area (IFA) (P&lt;0.05). However, the comparison between the two groups did not show statistically significant difference (P&gt;0.05). The presence of accessory canals should not be considered the only reason for inter-radicular pathological bone resorption following pulpal necrosis in deciduous molars.


2011 ◽  
Vol 47 (3) ◽  
pp. 605-613 ◽  
Author(s):  
Franciele Carla Prichoa ◽  
Silvane Souza Roman ◽  
Vanusa Manfredini

The use of plant species is emerging as an important alternative in the treatment of injuries. Therefore, the extract of Sonchus oleraceus 10% was employed in the repair of skin lesions. A total of 36 male Wistar rats were subjected to a punch injury and divided into three groups: a negative control, receiving no treatment, a positive control, treated with Dersani, and the experimental group treated with the extract. The injury was assessed macroscopically and microscopically. Morphometric data was collected at the 3rd, 5th and 7th postoperative day, and the experimental group showed greater changes in shrinkage of the lesion compared to control groups. On the 3rd postoperative day, the injury in the experimental group showed less necrotic tissue, lower slough and more granulation tissue in relation to the positive control group. On the 7th and 10th postoperative day, the injury in the experimental group showed lower slough compared to the positive control group. Microscopic analysis of lesions on the 5th postoperative day revealed increased fibroplasia in the experimental group compared to control groups, while on the 14th postoperative day less neovascularization was evident in the experimental group and increased formation of hair follicles in the negative control group. The extract of S. oleraceus provided tissue repair in accordance with normal physiological patterns thus confirming empirical evidence for its use.


2020 ◽  
Vol 44 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Zhihao Wang ◽  
Fei Sun ◽  
Yi Lu ◽  
Shu Pan ◽  
Wenlong Yang ◽  
...  

Objective: To shorten the preparation time of rabbit decellularized tracheal matrix through a modified detergent-enzymatic method with higher concentration of DNase (50 kU/mL), providing an experimental and theoretical basis for clinical decellularization technology. Methods: The control group was a natural trachea, and the experimental group was a tracheal matrix subjected to two and four decellularization cycles. The performance of each group of samples was evaluated by histology and immunohistochemical staining, scanning electron microscopy, biomechanical property testing, inoculation and cytotoxicity tests, and allograft experiments. Results: The results showed that the nuclei of the nonchondral areas of the tracheal stroma were essentially completely removed and MHC-I and MHC-II antigens were removed after two decellularization cycles. Histological staining and scanning electron microscopy showed that the extracellular matrix was retained and the basement membrane was intact. Cell inoculation and proliferation tests confirmed that the acellular tracheal matrix had good biocompatibility, and the proliferation capacity of bone mesenchymal stem cells on the matrix was increased in the experimental group compared with the control group ( p < 0.05). Histological staining and CD68 molecular marker analysis after the allograft experiment showed that the inflammatory response of the acellular tracheal matrix was weak and the infiltration of surrounding macrophages was reduced. Conclusion: A modified detergent-enzymatic method with an increased DNase (50 kU/mL) concentration requires only two cycles (4 days) to obtain a decellularized rabbit tracheal matrix with a short preparation time, good biocompatibility, suitable mechanical properties, and reduced preparation cost.


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