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Wound healing in diabetic patients presents significant challenges in clinical wound care due to high oxidative stress, excessive inflammation, and a microenvironment prone to infection. In this study, we successfully developed a multifunctional tandem dynamic covalently cross-linked hydrogel dressing aimed at diabetic wound healing. This hydrogel was constructed using cyanoacetic acid functionalized dextran (Dex-CA), 2-formylbenzoylboric acid (2-FPBA) and natural oligomeric proanthocyanidins (OPC), catalyzed by histidine. The resulting Dex-CA/OPC/2-FPBA (DPOPC) hydrogel can be dissolved triggered by cysteine, thereby achieving "controllable and non-irritating" dressing change. Furthermore, the incorporation of OPC as a hydrogel building block endowed the hydrogel with antioxidant and anti-inflammatory properties. The cross-linked network of the DPOPC hydrogel circumvents the burst release of OPC, enhancing its biosafety. In vivo studies demonstrated that the DPOPC hydrogel significantly accelerated the wound healing process in diabetic mice compared to a commercial hydrogel, achieving an impressive wound closure rate of 98 % by day 14. The DPOPC hydrogel effectively balanced the disrupted inflammatory state during the healing process. This dynamic hydrogel based on natural polyphenols is expected to be an ideal candidate for dressings intended for chronic wounds.
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Diabetes Mellitus Experimental , Hidrogéis , Proantocianidinas , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Proantocianidinas/química , Proantocianidinas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Reagentes de Ligações Cruzadas/química , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Dextranos/químicaRESUMO
The human body comprises various tubular structures that have essential functions in different bodily systems. These structures are responsible for transporting food, liquids, waste, and other substances throughout the body. However, factors such as inflammation, tumors, stones, infections, or the accumulation of substances can lead to the narrowing or blockage of these tubular structures, which can impair the normal function of the corresponding organs or tissues. To address luminal obstructions, stenting is a commonly used treatment. However, to minimize complications associated with the long-term implantation of permanent stents, there is an increasing demand for biodegradable stents (BDS). Magnesium (Mg) metal is an exceptional choice for creating BDS due to its degradability, good mechanical properties, and biocompatibility. Currently, the Magmaris® coronary stents and UNITY-BTM biliary stent have obtained Conformité Européene (CE) certification. Moreover, there are several other types of stents undergoing research and development as well as clinical trials. In this review, we discuss the required degradation cycle and the specific properties (anti-inflammatory effect, antibacterial effect, etc.) of BDS in different lumen areas based on the biocompatibility and degradability of currently available magnesium-based scaffolds. We also offer potential insights into the future development of BDS.
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Here, a reactive oxygen species (ROS)-responsive targeted anticancer drug delivery system was developed by embedding a nitrophenyl tetramethyl-dioxaborolanyl benzyl carbamate (NBC)-modified deoxyribonuclease I (DNase I) in a DNase-degradable aptamer-based DNA nanogel. The DNA nanogel was formed by hybridization of three types of building blocks, namely, Y-shaped monomer 1 with three sticky ends, Y-shaped monomer 2 with two sticky ends and an aptamer end, and a DNA linker with two sticky ends. Single doxorubicin (DOX) or ribonuclease A (RNase A) as well as the combination of DOX and RNase A were effectively loaded into the nanogels, wherein DOX was embedded into DNA skeleton, while RNase A was encapsulated into nanogel matrix. The blocked enzymatic activity of DNase I due to NBC modification could be restored upon intracellular ROS-triggered NBC deprotection, resulting in self-degradation of the nanogels to release both DOX and RNase A. Consequently, the DOX and RNase A coloaded nanogels significantly inhibited the proliferation of MCF-7 cells through a synergistic effect. To sum up, this DNA-based drug delivery system with ROS-responsive self-degradation properties should be promising for application in targeted and synergistic cancer therapy.
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Development of novel therapeutic agents that possess different anticancer mechanisms from the traditional antitumor drugs is highly attractive as no medication can cure all types of cancers. Herein, we report a rational design of antitumor lipo-polylysine polymers as synthetic mimics of biosynthetic lipopeptide surfactants featuring antimicrobial or cytotoxic activities for cancer therapy. The optimal polymer shows a wide range of anticancer activities against multiple cancer cells, including highly metastatic and drug-resistant ones, but low toxicity to normal cells. Mechanism studies show that the optimal polymer can interact with the membrane of cancer cells and induce cell necrosis by triggering cell membrane perforation, which is different from the therapeutic mechanisms of traditional anticancer drugs. In vivo studies imply that the optimal polymer efficiently inhibits tumor growth without causing obvious side effects on a C26 graft tumor model. Overall, the lipopeptide-mimicking lipo-polylysine with the advantages of easy synthesis and low cost provides a new anticancer strategy with high efficacy and biocompatibility.
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Antineoplásicos , Neoplasias , Humanos , Polilisina , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Lipopeptídeos , PolímerosRESUMO
Intrinsically disordered peptides drive dynamic liquid-liquid phase separation (LLPS) in membraneless organelles and encode cellular functions in response to environmental stimuli. Engineering design on phase-separating peptides (PSPs) holds great promise for bioimaging, vaccine delivery, and disease theranostics. However, recombinant PSPs are devoid of robust luminogen or suitable cell permeability required for intracellular applications. Here, we synthesize a peptide-based RNA sensor by covalently connecting tetraphenylethylene (TPE), an aggregation-induced emission luminogen (AIEgens), to tandem peptide repeats of (RRASL)n (n = 1, 2, 3). Interestingly, the conjugation of TPE luminogen promotes liquid-liquid phase separation of the peptide repeats, and the minimum coacervation concentration (MCC) of TPE-(RRASL)n is decreased by an order of magnitude, compared to that of the untagged, TPE-free counterparts. Moreover, the luminescence of TPE-(RRASL)n is enhanced by up to 700-fold with increasing RNA concentration, which is attributed to the constricted rotation of the TPE moiety as a result of peptide/RNA coacervates within the droplet phase. Besides, at concentrations above MCC, TPE-(RRASL)n can efficiently penetrate through human gallbladder carcinoma cells (SGC-996), translocate into the cell nucleus, and colocalize with intracellular RNA. These observations suggest that AIEgen-conjugated PSPs can be used as droplet-based biosensors for intracellular RNA imaging through a regime of coacervation-induced emission.
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Peptídeos , RNA , Humanos , LuminescênciaRESUMO
After anastomosis of sutures or pins, the restoration of intestinal barrier function can avoid several complications, such as tissue damage and inflammation. Our previous studies demonstrated the feasibility of biodegradable magnesium (Mg) pins as novel anastomosing implants to spontaneously absorb in the body, avoiding secondary removal surgery and long-term inflammation. However, the effect of Mg pins on the intestinal tight junction barrier is rarely investigated. In this study, we conducted high-purity Mg pins inserted in the intestine of rats and prepared Mg extracts cultured intestinal epithelial cell line to investigate the biological effect on the intestinal barrier associated with tight junction protein expression. We discovered that the concentration of released Mg ions over 1.7 mM was the critical threshold, above which mRNA expression of intestinal tight junction and cell apoptosis were affected considerably. Results of the immunohistochemical analysis revealed that Mg functions to stimulate ZO-1, caspase-3, occluding, and claudin-3 expressions. We offer new insight into the effectiveness of biodegradable Mg materials as the next generation of intestinal anastomosis pins, which effectively filters toxins as well as bacteria, and reduces inflammation.
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Magnésio , Junções Íntimas , Animais , Ratos , Magnésio/farmacologia , Junções Íntimas/metabolismo , Mucosa Intestinal/metabolismo , Intestinos , Células Epiteliais/metabolismo , InflamaçãoRESUMO
BACKGROUND: Implantable Collamer lens (ICL) vaulting is one of the most important parameters for the safety, aqueous humor circulation, and lens transparency after ICL implantation. This study aimed to investigate the factors associated with the actual vaulting after refractive EVO-ICL surgery. METHODS: This retrospective study included patients who underwent EVO-ICL surgery at a tertiary eye hospital between October and December 2019. A RESCAN 700 was used for the intraoperative and CIRRUS HD-OCT was used for postoperative observation of vaulting. Subjective and objective refractions, anterior ocular segment, corneal morphology, intraocular pressure (IOP), anterior chamber volume (ACV), crystalline lens rise (CLR), white-to-white distance (WTW), anterior chamber depth (ACD), axial length, corneal endothelial cell density (ECD), and fundoscopy were examined. A multivariable analysis was performed to determine the factors independently associated with 1-month postoperative vaulting. RESULTS: Fifty-one patients (102 eyes) were included. Compared with the eyes with normal vaulting, those with high vaulting had higher preoperative diopter values (P = 0.039), lower preoperative corrected visual acuity (P = 0.006), lower preoperative IOP (P = 0.029), higher preoperative ACD (P = 0.004), lower preoperative CLR (P = 0.046), higher ICL spherical equivalent (P = 0.030), higher intraoperative vaulting (P < 0.001), and lower IOP at 1 month (P = 0.045). The multivariable analysis showed that the only factor independently associated with high vaulting at 1 month after surgery was the intraoperative vaulting value (odds ratio = 1.005, 95% confidence interval: 1.002-1.007, P < 0.001). The intraoperative and 1-month postoperative vaulting values were positively correlated (R2 = 0.562). CONCLUSIONS: The RESCAN700 system can be used to perform intraoperative optical coherence tomography to predict the vaulting value of ICL at 1 month.
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Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular , Miopia/cirurgia , Refração Ocular , Estudos RetrospectivosRESUMO
OBJECTIVE: In recent years, biportal endoscopic lumbar interbody fusion (BE-LIF) has been increasingly used in the treatment of lumbar degenerative diseases. BE-LIF combines the benefits of minimally invasive fusion with endoscopic spine surgery. However, there is little evidence on whether BE-LIF is superior to posterolateral lumbar interbody fusion (PLIF). The purpose of this meta-analysis is to compare the clinical outcomes, complications, and fusion rates of BE-LIF and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)/PLIF in treating lumbar degenerative diseases. METHODS: A comprehensive assessment of the literature was conducted, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa Scale. Clinical parameters were investigated using a visual analog scale (VAS) for pain levels and the Oswestry Disability Index for disability levels. The operative times, estimated blood loss, fusion rates, and complications were also analyzed. RESULTS: This meta-analysis comprised 5 studies with a total of 444 participants. No significant differences between the techniques were seen in VAS scores for legs, Oswestry Disability Index, complications, or fusion rates. There were significantly lower VAS scores for back pain in the BE-LIF group than the MI-TLIF/PLIF group, postoperatively. In addition, BE-LIF resulted in significantly less blood loss but required a longer operative time than did MI-TLIF/PLIF. CONCLUSIONS: The benefits of BE-LIF and MI-TLIF/PLIF were approximately equivalent in terms of clinical outcomes and achievement of fusion, and complication rates were similar in both groups. However, BE-LIF reduced postoperative back pain and blood loss, despite longer operative times.
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Vértebras Lombares , Fusão Vertebral , Endoscopia , Humanos , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 µL/mm3 per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.
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Biodegradable magnesium (Mg) implants spontaneously releasing therapeutic agents against tumors are an intriguing therapeutic approach for both tissue repair and tumor treatment. Anastomotic staples are extensively used for wound closure after surgical resection in patients with colorectal tumors. However, the safety of Mg anastomosis implants for intestinal closure and the effect of tumor suppression remain elusive. Here, we used a high-purity Mg staple to study these issues. Based on the results, we found that it has the potential to heal wounds produced after colorectal tumor resection while inhibiting relapse of residual tumor cells in vitro and in vivo. After implantation of Mg staples for 7 weeks in rabbits, the intestinal wound gradually healed with no adverse effects such as leakage or inflammation. Furthermore, the implanted Mg staples inhibit the growth of colorectal tumor cells and block migration to normal organs because of the increased concentration of Mg ions and released hydrogen. Such an antitumor effect is further confirmed by the in vitro cell experiments. Mg significantly induces apoptosis of tumor cells as well as inhibits cell growth and migration. Our work presents a feasible therapeutic opinion to design Mg anastomotic staples to perform wound healing and simultaneously release tumor suppressor elements in vivo to decrease the risk of tumor recurrence and metastasis.
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Magnésio , Recidiva Local de Neoplasia , Anastomose Cirúrgica , Animais , Humanos , Magnésio/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Coelhos , Grampeamento Cirúrgico , SuturasRESUMO
Gallbladder cancer can be difficult to detect in its early stages and is prone to metastasize, causing bile duct obstruction, which is usually treated by stent implantation in clinic. However, the commonly used biliary stents are non-degradable, which not only prone to secondary blockage, but also need to be removed by secondary surgery. Biodegradable magnesium (Mg) is expected to one of the promising candidates for degradable biliary stents due to its excellent physicochemical property and biocompatibility. In this work, we studied the influence of high-purity Mg wires on gallbladder cancer through in vitro and in vivo experiments and revealed that the degradation products of Mg could significantly inhibit the growth of gallbladder cancer cells and promote their apoptosis. Our findings indicate that Mg biliary stent possesses the function of draining bile and treating gallbladder cancer, suggesting that Mg has good application prospects in biliary surgery. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical magnesium are mainly concentrated in the cardiovascular and orthopedics field. Degradable magnesium bile duct stents have great application prospects in the treatment of bile duct blockage caused by bile duct-related cancers. At present, the effect of magnesium implants on gallbladder cancer is not clear. Our work verified the effectiveness of magnesium wire implants in inhibiting gallbladder cancer through in vivo and in vitro experiments, and studied the effect of magnesium degradation products on gallbladder cancer cells from the perspective of cell proliferation, apoptosis and cycle. This study provided new understanding for the application of magnesium in biliary surgery.
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Neoplasias da Vesícula Biliar , Implantes Absorvíveis , Ductos Biliares , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Magnésio/farmacologia , StentsRESUMO
Distraction osteogenesis has widespread clinical use in the treatment of large bone defects. Nonetheless, the prolonged consolidation period carries the risk of complications. Magnesium-based materials have been shown to promote bone regeneration in fracture healing both in vitro and in vivo. Here, we investigated whether high-purity magnesium could enhance bone formation in distraction osteogenesis. High-purity magnesium pins were placed into the medullary cavity in the rat distraction osteogenesis model. Results showed that the bone volume/total tissue volume, bone mineral density, and mechanical properties of new callus were significantly higher in the high-purity magnesium group compared to stainless steel and control group (p < 0.01). Histological analyses confirmed improved bone consolidation and vascularization in high-purity magnesium group. Further, polymerase chain reaction-array investigation, Western blot, and immunohistochemical results found that vascular endothelial growth factor and hypoxia inducible factor-1α were highly expressed in the high-purity magnesium group, while Von Hippel-Lindau protein was the opposite (p < 0.01). In conclusion, high-purity magnesium implants have the potential to enhance angiogenesis and bone consolidation in the distraction osteogenesis application, and this process might be via the regulation of Von Hippel-Lindau/hypoxia inducible factor-1α/vascular endothelial growth factor signaling.
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Materiais Biocompatíveis/farmacologia , Pinos Ortopédicos , Magnésio/farmacologia , Osteogênese por Distração , Osteogênese/efeitos dos fármacos , Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Animais , Materiais Biocompatíveis/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Magnésio/química , Masculino , Osteogênese por Distração/métodos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
The common treatment of epithelial ovarian cancer is aggressive surgery followed by platinum-based cytotoxic chemotherapy. However, residual tumor cells are resistant to chemotherapeutic drugs during postoperative recurrence. The treatment of ovarian cancer requires breakthroughs and advances. In recent years, magnesium alloy has been widely developed as a new biodegradable material because of its great potential in the field of medical devices. From the degradation products of magnesium, biodegradable magnesium implants have great potential in antitumor. According to the disease characteristics of ovarian cancer, we choose it to study the antitumor characteristics of biodegradable magnesium. We tested the anti-ovarian tumor properties of Mg through both in vivo and in vitro experiments. According to the optical in vivo imaging and relative tumor volume statistics of mice, high-purity Mg wires significantly inhibited the growth of SKOV3 cells in vivo. We find that the degradation products of Mg, Mg2+, and H2 significantly inhibit the growth of SKOV3 cells and promote their apoptosis. Our study suggests a good promise for the treatment of ovarian cancer.
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Recidiva Local de Neoplasia , Neoplasias Ovarianas , Implantes Absorvíveis , Animais , Apoptose , Carcinoma Epitelial do Ovário , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
Little attention has been paid to the biocompatibility and biological effects of zinc as a material. Here, we therefore investigated the biocompatibility and anti-inflammatory and collagen-promoting effects of pure zinc material in the colorectum. Our in vitro results indicated that zinc toxicity and concentration were closely related. Low concentrations of zinc ions and pure zinc material extract had only minor effects on the viability of primary rectal mucosal epithelial cells; however, cytotoxicity was observed at concentrations greater than 0.017 µg/µL and 60%, respectively. In vivo experiments demonstrated that zinc pins degraded slowly in the colorectum (their volume decreasing by approximately 7.79% over 1 month) and did not cause serious adverse reactions. Pure zinc material was found to inhibit acute inflammation through increased expression of ENA-78 and F4/80. Moreover, zinc material heightened expression of collagen and VEGF, factors conducive to wound healing, in surrounding colorectal tissues. These preliminary results suggest that zinc shows great promise as an implant material for medical applications involving colorectal surgery.
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Titanium (Ti) staples are not biodegradable, and anastomotic complications related to Ti staples are reported frequently. In the present study, the biocompatibility and degradation behavior of high-purity magnesium (HP Mg) staples with the small intestine were investigated. HP Mg staples did not affect the relative growth rate, cell cycle and apoptosis of primary rectal mucosal epithelial cells (IEC-6) in vitro. At one, two and three days after immersion in intestinal juice, the weight of the 30 rinsed HP Mg staples reduced by 7.5 ± 1.6, 10.6 ± 2.2 and 13.5 ± 2.1 mg, respectively, and those in the Hanks' solution reduced by 3.9 ± 0.8, 6.1 ± 1.2 and 7.1 ± 2.4 mg. Extracts of HP Mg staples were bio-safe for IEC-6, and the corrosion rate of HP staples was faster in the small intestinal juice than in the Hanks' solution. In the in vivo experiments, the small intestine of the minipigs was anastomosed by HP Mg and Ti staples. HP Mg staples neither affected important bio-chemical parameters nor induced serious inflammation or necrosis in the anastomosis tissues. The residual weight of a HP Mg staples (0.81 ± 0.13 mg) was 89.7% of the original weight (9 ± 0.09 mg) one month after surgery. The in vivo corrosion rate for one HP Mg staple was determined to beâ¼0.007 ± 0.001 mm·month-1. The preliminary results of the biocompatibility and degradation of high-purity Mg anastomotic staples are promising, and further studies will be initiated to study in more detail.
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Implantes Absorvíveis , Anastomose Cirúrgica/instrumentação , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Intestino Delgado/cirurgia , Suturas , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Suínos , Porco Miniatura , Resultado do TratamentoRESUMO
Patients after anterior cruciate ligament (ACL) reconstruction surgery commonly encounters graft failure in the initial phase of rehabilitation. The inhibition of graft degradation is crucial for the successful reconstruction of the ACL. Here, we used biodegradable high-purity magnesium (HP Mg) screws in the rabbit model of ACL reconstruction with titanium (Ti) screws as a control and analyzed the graft degradation and screw corrosion using direct pull-out tests, microCT scanning, and histological and immunohistochemical staining. The most noteworthy finding was that tendon graft fixed by HP Mg screws exhibited biomechanical properties substantially superior to that by Ti screws and the relative area of collagen fiber at the tendon-bone interface was much larger in the Mg group, when severe graft degradation was identified in the histological analysis at 3 weeks. Semi-quantitative immunohistochemical results further elucidated that the MMP-13 expression significantly decreased surrounding HP Mg screws with relatively higher Collagen II expression. And HP Mg screws exhibited uniform corrosion behavior without displacement or loosening in the femoral tunnel. Therefore, our results demonstrated that Mg screw inhibited graft degradation and improved biomechanical properties of tendon graft during the early phase of graft healing and highlighted its potential in ACL reconstruction.
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Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/instrumentação , Magnésio/farmacologia , Implantes Absorvíveis , Animais , Lesões do Ligamento Cruzado Anterior/metabolismo , Reconstrução do Ligamento Cruzado Anterior/métodos , Fenômenos Biomecânicos , Parafusos Ósseos , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Sobrevivência de Enxerto , Humanos , Metaloproteinase 13 da Matriz/metabolismo , Coelhos , Titânio/efeitos adversosRESUMO
Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a biodegradable interference screw with the potential to promote fibrocartilaginous entheses regeneration in ACL reconstruction.
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Reconstrução do Ligamento Cruzado Anterior/métodos , Proteína Morfogenética Óssea 2/metabolismo , Parafusos Ósseos , Fibrocartilagem/patologia , Magnésio/farmacologia , Regeneração/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos/efeitos dos fármacos , Western Blotting , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Sobrevivência Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Modelos Animais de Doenças , Fibrocartilagem/diagnóstico por imagem , Glicosaminoglicanos/metabolismo , Humanos , Imuno-Histoquímica , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Coelhos , Amplitude de Movimento Articular/efeitos dos fármacos , Tendões/efeitos dos fármacos , Tendões/patologia , Cicatrização/efeitos dos fármacos , Microtomografia por Raio-XRESUMO
Biodegradable magnesium alloy implants have attracted much attention because of their excellent biocompatibility and good mechanical properties. However, effects of Mg alloy on cell apoptosis remain unclear. The aim of this study was to investigate the effects of the Mg-6Zn alloy on the apoptosis and necrosis of common bile duct (CBD) epithelial cells. In the in vitro experiments, primary mouse extrahepatic bile epithelial cells (MEBECs) were exposed to Mg-6Zn alloy extracts with different concentrations (0, 40, 80, and 100 %). Flow cytometry analysis indicated that low concentration Mg-6Zn extract can induce apoptosis of MEBECs, and high concentration Mg-6Zn extracts may relate to necrosis and/or 'apoptotic necrosis'. Real-time PCR results showed that when MEBECs were treated with 40 % extracts for 3 days, the relative apoptotic genes including Bax, Bax/Bcl-2 ratio, NF-κB and caspase-3 were higher than those in the control group. In the in vivo experiments, Mg-6Zn alloy stents were implanted into rabbits' CBD for 1, 2, 3 weeks, respectively. Based on the hematoxylin and eosin (H&E) staining of peri-implant CBD tissue, no apoptotic bodies and necrotic cells were observed. Results of immunohistochemical staining also showed Mg-6Zn stents did not increase expression levels of apoptosis related gene such as Bax, Bcl-2, Bax/Bcl-2 ratio, TNF-α, NF-κB and caspase-3 in CBD, which indicating Mg-6Zn did not induce significant apoptosis in the in vivo experiments. The different results of in vitro and in vivo experiment may result from the low corrosion rate of Mg-6Zn alloy stents in vivo and local Mg(2+) ion concentration in CBD.
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Materiais Biocompatíveis/farmacologia , Ducto Colédoco/citologia , Células Epiteliais/efeitos dos fármacos , Stents , Implantes Absorvíveis , Ligas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Ducto Colédoco/cirurgia , Citometria de Fluxo , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Coelhos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
To evaluate the different effects of Mg-6Zn alloy and Ti-3Al-2.5V alloy implants in intestinal tract healing, we compared these two different alloys with respect to their effect on a rat's intestinal tract, using serum magnesium, radiology, pathology and immunohistochemistry in vivo. It was found using the scanning electron microscope that the Mg-6Zn alloy began to degrade during the first week and that the Ti-3Al-2.5V alloy was non-degradable throughout the process. The Mg-6Zn alloy did not have an impact on serum magnesium. Superior to the Ti-3Al-2.5V alloy, the Mg-6Zn alloy enhanced the expression of transforming growth factor-ß1 in healing tissue, and promoted the expression of both the vascular endothelial growth factor and the basic fibroblast growth factor, which helped angiogenesis and healing. The Mg-6Zn alloy reduced the expression of the tumor necrosis factor (TNF-α) at different stages and decreased inflammatory response, which may have been related to the zinc inhibiting TNF-α. In general, the Mg-6Zn alloy performed better than Ti-3Al-2.5V at promoting healing and reducing inflammation. The Mg-6Zn alloy may be a promising candidate for use in the pins of circular staplers for gastrointestinal reconstruction in medicine.
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Ligas/química , Fator 2 de Crescimento de Fibroblastos/metabolismo , Mucosa Intestinal/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alumínio/química , Animais , Materiais Biocompatíveis/química , Inflamação , Magnésio/química , Masculino , Teste de Materiais , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley , Titânio/química , Vanádio/química , Cicatrização , Zinco/químicaRESUMO
To evaluate the ability of Mg-6Zn to replace titanium nails in the reconstruction of the intestinal tract in general surgery, we compared the Mg-6Zn and titanium implants with respect to their effects on rat's intestinal tract by biochemical, radiological, pathological and immunohistochemical methods. The results indicated that Mg-6Zn implants started to degrade at the third week and disintegrate at the fourth week. No bubbles appeared, which may be associated with intestinal absorption of the Mg-6Zn implants. Pathological analyses (containing liver, kidney and cecum tissues) and biochemical measurements, including serum magnesium, creatinine, blood urea nitrogen, glutamic-pyruvic-transaminase and glutamic-oxaloacetic-transaminase proved that degradation of Mg-6Zn did not harm the important organs, which is an improvement over titanium implants. Immunohistochemical results showed that Mg-6Zn could enhance the expression of transforming growth factor-ß1. Mg-6Zn reduced the expression of tumor necrosis factor at different stages. In general, our study demonstrates that the Mg-6Zn alloy had good biocompatibility in vivo and performed better than titanium at promoting healing and reducing inflammation. It may be a promising candidate for stapler pins in intestinal reconstruction.