Use of a new elastin patch and glue for repair of a major duodenal injury

Major duodenal injury with significant tissue loss causes high morbidity and mortality. Our new elastin based heterograft combined with small intestinal submucosa (SIS) and biodegradable glue could be used for repair of such defects. Twenty-four domestic pigs were anesthetized and underwent celiotomy. A 2 cm circular defect was created at the second portion of the duodenum with scissors, excising one-half of its circumference. Our elastin patch, combined with SIS, was applied to cover the defect using biodegradable cyanoacrylate glue and a few sutures. It was then covered with omentum. Animals were followed by weight gain, endoscopic evaluation, and upper GI barium studies. After 2-5 months, animals were sacrificed to obtain specimens. One failed in 3 days due to a technical problem, and one failed in 20 days due to an abdominal abscess. The other 22 animals (22/24, 91.7%) did well, gaining weight. Early endoscopic studies (5-14 d) showed an intact patch. Upper GI studies showed varying degrees of stenosis at the repair site at 3-4 months. Sacrifice after 2-5 months showed complete healing of the defect and a dissolved patch. Our new elastin patch material provides a reliable barrier for repair of duodenal injury, and the biodegradable glue provides quick and easy watertight tissue fusion for our patch.     

The zebrafish swimbladder: A simple model for lung elastin injury and repair

In this communication we offer data to suggest that the zebrafish swimbladder may provide a simple model of elastin injury and repair which is amenable to genetic analysis and pertinent to lung physiology. In situ hybridization of zebrafish embryos illustrated that elastin gene expression is evident in the developing gut tract prior to swimbladder morphogenesis. Northern blot analysis demonstrated that the major zebrafish elastin mRNA is 2.0 kb which is significantly smaller than its higher vertebrate counterpart. Amino acid analysis of alkali-resistant protein from the anterior chamber of the adult zebrafish swimbladder showed a composition similar to higher vertebrate elastins including significant amounts of desmosine crosslinks. Electron microscopic investigations of the swimbladder wall indicate a simple structure with an inner layer of elastin fibers. Elastase delivery to the swimbladder in vitro resulted in significant fragmentation of elastin in the anterior chamber providing an environment for studying elastin repair within the tissue.     

生物材料修复半月板运动损伤

背景：目前运用人工生物材料干预软骨损伤后愈合与康复的手段日趋成熟与多样,为半月板康复提供了崭新的研究方向。 目的：对半月板运动损伤机制进行探讨,分析生物材料在半月板损伤修复中的作用。 方法：由第一作者检索 1990/2010 PubMed数据及CNKI数据库,选择文章内容与半月板损伤、人工材料治疗措施等相关的文献。 结果与结论：人工生物材料在具体实践运用过程中,由于必须考虑其与人体的生物相容性、形状的匹配、附着性、韧性、强度等,选择理想的植入物较为困难。目前修复半月板应用较多的生物材料主要有透明质酸、胶原、明胶、聚羟乙酸、聚乳酸、聚磷酸钙、不可吸收的聚四氟乙烯、碳素纤维聚合物等。将干细胞定向诱导或经转化生长因子β1基因修饰,通过调节多种细胞的生长和分化,诱导骨髓间充质干细胞向软骨细胞方向分化,并接种于生物支架材料上,为半月板的损伤康复提供了崭新的研究方向。     

Mechanical evaluation and design of a multilayered collagenous repair biomaterial

One method of fabricating implantable biomaterials is to utilize biologically derived, chemically modified tissues to form constructs that are both biocompatible and remodelable. Rigorous mechanical characterization is a necessary component in material evaluation to ensure that the constructs will withstand in vivo loading. In this study we performed an in-depth biaxial mechanical and quantitative structural analysis of GraftPatch (GP), a biomaterial constructed by assembling chemically treated layers of porcine small intestinal submucosa (SIS). The mechanical behavior of GP was compared to both native SIS and to glutaraldehyde-treated bovine pericardium (GLBP) as a reference biomaterial. Under biaxial loading, GP was found to be stiffer than native SIS and mechanically anisotropic, with the preferred fiber direction demonstrating greater stiffness. Quantitative structural analysis using small-angle light scattering indicated a uniform fiber structure similar to GLBP and SIS. To enable test-protocol-independent quantitative comparisons, the biaxial mechanical data were fit to an orthotropic constitutive model, which indicated a similar degree of mechanical anisotropy between the three groups. We also demonstrate how the constitutive model can be used to design layered biocomposite materials that can undergo large deformations.     

A biomaterial composed of collagen and solubilized elastin enhances angiogenesis and elastic fiber formation without calcification

Elastin is the prime protein in elastic tissues that contributes to elasticity of, for example, lung, aorta, and skin. Upon injury, elastic fibers are not readily replaced, which hampers tissue regeneration. Incorporation of solubilized elastin (hydrolyzed insoluble elastin fibers or elastin peptides) in biomaterials may improve regeneration, because solubilized elastin is able to promote proliferation as well as elastin synthesis. Porous biomaterials composed of highly purified collagen without and without elastin fibers or solubilized elastin were prepared by freezing and lyophilization. Solubilized elastin formed spherical structures that were incorporated in the collagenous part of the scaffolds and that persisted after chemical crosslinking of the scaffolds. Crosslinked scaffolds were subcutaneously implanted in young Sprague Dawley rats. Collagen-solubilized elastin and collagen scaffolds showed no calcification in this sensitive calcification model, in contrast to scaffolds containing elastin fibers. Collagen-solubilized elastin scaffolds also induced angiogenesis, as revealed by type IV collagen staining, and promoted elastic fiber synthesis, as shown with antibodies against rat elastin and fibrillin-1. It is concluded that scaffolds produced from collagen and solubilized elastin present a non-calcifying biomaterial with a capacity for soft-tissue regeneration, especially in relation to elastic fiber synthesis.     

Development of an infection-resistant bifunctionalized Dacron biomaterial

A novel infection-resistant biomaterial was created by applying the antibiotic Ciprofloxacin (Cipro) to a recently developed bifunctionalized polyethylene terephthalate ("polyester," Dacron) material using textile-dyeing technology. Dacron was modified via exposure to ethylenediamine (EDA) to create amine and carboxylic acid sites within the polymer backbone. Cipro was applied to the bifunctionalized Dacron construct under varied experimental conditions, with resulting antimicrobial activity determined via zone of inhibition. Dacron segments treated at a liquor ratio of 20:1, with 5% Cipro on weight of fabric (owf), at pH 8 for 4 h at 70 degrees C followed by autoclaving showed antimicrobial activity for 78 days (length of study). Segments treated similarly but without autoclaving lost activity within 1 day. Dyeing time and temperature did not significantly affect antibiotic release/activity, but segments dyed at pHs higher or lower than 8 had less antimicrobial activity. The long-term infection resistance provided by this technique may answer major problems of infection from which implantable Dacron biomedical devices suffer.     

Comparison and characterization of multiple biomaterial conduits for peripheral nerve repair

Four biomaterial tubes, poly(lactic-co-glycolic acid) (PLGA), poly(caprolactone fumarate) (PCLF), a neutral oligo[(polyethylene glycol) fumarate] (OPF) hydrogel or a positively charged oligo[(polyethylene glycol) fumarate] (OPF⁺) hydrogel with a PCLF sleeve, have previously been shown to have benefits for nerve repair. However, no direct comparison to identify the optimal material have been made. Herein, these nerve tubes were implanted in a rat sciatic nerve model and nerve regeneration was quantified and compared by using accepted nerve assessment techniques. Using standard statistical methods, no significant differences of individual parameters were apparent between groups despite PCLF showing a tendency to perform better than the others. Using a mean–variance based ranking system of multiple independent parameters, statistical differences became apparent. It was clear that the PLCF tube supported significantly improved nerve regeneration and recovery compared to the other three biomaterial conduits. The ability to simultaneously compare a number of regenerative parameters and elucidate the best material from the combination of these individual parameters is of importance to the nerve regeneration area and has implications for the tissue engineering field. By using this method of comparison, a number of biomaterial constructs may be compared under similar conditions and the optimal construct elucidated using the minimal number of animals and materials.     

Development of an artificial vertebral body using a novel biomaterial,hydroxyapatite/collagen composite

Hydroxyapatite/collagen (HAp/Col) composites having a bone-like nanostructure were synthesized and shaped into implants. This study was designed to develop an artificial vertebra system using this novel implant for anterior fusion of the cervical spine. Anterior fusion was carried out on 6 beagle dogs with the implants adsorbing rhBMP-2 (400 microg/ml). and 9 dogs with the implants without rhBMP-2. In 3 dogs of the rhBMP-treated group, as well as 6 dogs of the non-rhBMP-treated group, the implant was fixed with a poly-L-lactide plate and 2 titanium screws. Implants were taken out after 13 weeks from each 3 dogs in the rhBMP(-):plate(-). rhBMP(-):plate(+) and rhBMP(+):plate(+) groups. Also, the implants were removed from each 3 dogs in the rhBMP(-):plate(+) and rhBMP(+):plate(+) groups after 24 weeks. Histological and radiographical analysis suggested that since the larger part of the composite material was absorbed within 13 weeks, reduction of the intervertebral distance was caused, and that enhancement of callus formation and bone bridging by rhBMP-treatment was effective to prevent collapse of the implant, even though an effect of anterior plate-fixation was not obvious. The HAp/Col implant adsorbing rhBMP-2 may be a suitable replacement for the existing ceramics in anterior interbody fusion of the cervical spine.     

生物材料支架在治疗脊髓损伤中的应用

背景:由于脊髓损伤后神经神经再生能力弱,修复受损脊髓组织并使其实现功能正常化仍是目前医学难题。生物组织材料学的快速发展以及其在医学中广泛应用为脊髓损伤修复提供了新的治疗理念和方法。目的:总结生物材料支架对脊髓损伤后神经组织再生修复研究并对其发展趋势进行展望,以探讨修复脊髓损伤的方法并总结经验。方法:应用PubMed数据库高级检索功能,检索2011年1月至2021年1月的文献,检索词为“Spinal cord injury;Biomaterials;Nerve regeneration;Material”;应用知网、万方、维普等数据库高级检索功能,检索2011年1月至2021年1月的相关文献,检索词为“脊髓损伤;生物材料;支架”。结果与结论:随着生物工程研究和医学结合的进一步深入,生物材料支架已被广泛应用于脊髓损伤修复的研究,生物材料的组织相容性、降解性等方面均有了改善;生物材料种类较多,各有其利弊,取其优点制备成复合支架并负载种子细胞、细胞因子或药物对神经再生效果更佳。但复合支架如何选择材料组合,如何选择种子细胞、细胞因子或药物,使生物材料支架联合种子细胞、细胞因子或药物成为最佳组合值得深入研究。总之,生物材料修复脊髓损伤是一个新思路,可能成为促进脊髓损伤修复的突破点。     

An in vivo study of a gold nanocomposite biomaterial for vascular repair

Currently vascular repairs are treated using synthetic or biologic patches, however these patches have an array of complications, including calcification, rupture, re-stenosis, and intimal hyperplasia. An active patch material composed of decellularized tissue conjugated to gold nanoparticles (AuNPs) was developed and the long term biocompatibility and cellular integration was investigated. Porcine abdominal aortic tissue was decellularized and conjugated with 100 nm gold nanoparticles (AuNP). These patches were placed over a longitudinal arteriotomy of the thoracic aorta in six pigs. The animals were monitored for six months. Gross, histological, and immunohistochemical analyses of the patches were performed after euthanasia. Grossly there was minimal scar tissue with the patches still visible on the outer surface of the vessel. The inner lumen was smooth with a seamless transition from patch to native tissue. Histology demonstrated infiltration of host cells into the patch material. The immunohistochemical results demonstrated an endothelial cell layer forming over the patch within the vessel. Smooth muscle cells were repopulating the biomaterial in all animals. These results demonstrated that the AuNP biomaterial patch integrated well with the host tissue and did not failed over the six month implantation time.     

Tissue repair: an important determinant of final outcome of toxicant-induced injury

Tissue repair is a dynamic compensatory cell proliferation and tissue regeneration response stimulated in order to overcome acute toxicity and recover organ/tissue structure and function. Extensive evidence in rodent models using structurally and mechanistically diverse hepatotoxicants such as acetaminophen (APAP), carbon tetrachloride (CCl4), chloroform (CHCl3), thioacetamide (TA), trichloroethylene (TCE), and allyl alcohol (AA) have demonstrated that tissue repair plays a critical role in determining the final outcome of toxicity, i.e., recovery from injury and survival or progression of injury leading to liver failure and death. Tissue repair is a complex process governed by intricate cellular signaling involving a number of chemokines, cytokines, growth factors, and nuclear receptors leading to promitogenic gene expression and cell division. Tissue repair also encompasses regeneration of hepatic extracellular matrix and angiogenesis, the processes necessary to completely restore the structure and function of the liver tissue lost to toxicant-induced initiation followed by progression of injury. New insights have emerged over the last quarter century indicating that tissue repair follows a dose response. Tissue repair increases with dose until a threshold dose, beyond which it is delayed and impaired due to inhibition of cellular signaling resulting in runaway secondary events causing tissue destruction, organ failure, and death. Prompt and adequately stimulated tissue repair response to toxic injury is critical for recovery from toxic injury. Tissue repair is modulated by a variety of factors including species, strain, age, nutrition, and disease condition causing marked changes in susceptibility and toxic outcome. This review focuses on the properties of tissue repair, different factors affecting tissue repair, and the mechanisms that govern tissue repair and progression of injury. It also highlights the significance of tissue repair as a target for drug development strategies and an important consideration in the assessment of risk from exposure to toxicants.     

Effect of crosslinking on the performance of a collagen-derived biomaterial as an implant for soft tissue repair: a rodent model

One of the main problems in healthcare is the loss of tissues resulting from diseases, post-surgery complications or trauma. As a result there is a need for biomaterials designed to promote tissue regeneration and improve wound healing. This study assessed the effect of crosslinking of a porcine dermal collagen matrix with regard to strength of implant/host tissue integration, implant biocompatibility and general healing in a rodent model. Permacol?, a crosslinked acellular collagenous biomaterial was compared with its noncrosslinked equivalent at 3, 6, and 12 months postsubcutaneous implantation. Both matrices were well tolerated and showed no evidence of inflammation or adverse responses either in the host tissue or implants. Progressive integration of the implants with the surrounding tissue was observed. Cellular response was similar for both collagenous matrices although, at 3 and 6 months, noncrosslinked implants showed a significantly higher level of cellular penetration than crosslinked implants. However, at 12 months crosslinked implants showed significantly higher levels of cellular density, neo-vascularisation and integration with host tissue. Additionally, at long term, noncrosslinked implants lost volume suggesting some absorption. The crosslinking process does not seem to be detrimental to cellular response and biocompatibility.     

牛心包补片修复心脏间隔缺损的应用

背景：心脏涤纶补片因其质地薄、质量轻、生物相容性好等优点常规用于心脏手术,但最近几年发现,用心脏涤纶补片对心室间隔缺损修补后,一旦发生术后残余漏,较易引起溶血、细菌或真菌感染。 目的：探讨应用牛心包补片修复心脏间隔缺损的疗效。 方法：采用戊二醛固定的牛心包补片修补152例心脏间隔缺损患者,其中房间隔缺损56例,室间隔缺损78例,部分房室间隔缺损18例。术后复查心电图、胸片、心脏超声,观察其术后早期病情、血流动力学和心脏功能。 结果与结论：152例患者均完成修补手术,术后无早期死亡,患者随访2-6个月,牛心包补片在使用过程中及术后早期均未发现漏血、溶血、血栓、感染、排斥反应等并发症。1例患者因合并肺动脉高压,术后第1天出现高血压危象,经过抢救后好转。复查心电图、胸片、心脏超声可见心脏间隔缺损修补完全,无残余分流;肺动脉压力明显下降;活瓣已关闭无分流;心脏功能正常。证实牛心包补片可以有效修复心脏间隔缺损,改善患者的血流动力学和心功能,近期效果满意,是一种良好的心脏间隔缺损修补材料。     

Development of transmucosal patch using nanofibers

In the present work we have attempted to develop a novel transmucosal patch of diclofenac sodium using electrospun polycaprolactone (PCL) nanofibers. PCL nanofibers were prepared by electrospinning techniques using different polymer concentrations. Nanofibers formulations were characterized by SEM, FTIR, drug loading, and in-vitro release study using Franz diffusion cell. Studies revealed the nanofibers fabricated from 13% PCL were fracture-free, non-beaded, and ultrafine with 120 nm diameter. Release studies demonstrated the sustained release behavior of PCL nanofibers. Nanofibers can be exploited for transmucosal drug delivery of NSAID with improved therapeutic efficacy.     

组织工程牛心包补片在法洛四联症分期矫治中的应用

背景：行法洛四联症矫治手术时,对右室流出道狭窄较严重的病例,常需要行右室流出道补片加宽成形,目前采用的加宽材料有生物补片及人造织物补片等。 目的：比较涤纶人造血管片和组织工程牛心包补片在法洛四联症分期矫治手术中加宽右室流出道的早期临床效果。 方法：25例已行一期分流手术后再行二期心内矫治的法洛四联症患者,按照不同的二期手术时间分为两组：2007年4月至2010年7月接受二期手术的14例患者以涤纶人造血管片加宽右室流出道;2010年8月至2011年9月接受二期手术的11例患者,采用商品化的组织工程牛心包补片加宽右室流出道。比较两组术后早期的临床效果。 结果与结论：25例患者中,仅涤纶人造血管片组术后死亡1例,术后开胸止血1例,所有均未出现免疫排斥反应和毒性反应。组织工程牛心包补片组术后呼吸机使用时间、体外循环稳定后测量的右心室与左心室收缩压比值、右心室流出道压差、心包腔引流量、术后ICU治疗时间和术后住院天数均少于涤纶人造血管片组(P < 0.05)。说明采用组织工程牛心包补片加宽右室流出道的患者术后恢复较采用涤纶人造血管片的患者快,右室流出道疏通效果好,提示组织工程牛心包补片是法洛四联症患者分期矫治手术中加宽右室流出道的一种较理想材料。     

Synthesis and characterization of L-tyrosine based polyurethanes for biomaterial applications

The use of amino acid based polymers for biomaterial applications enhance biocompatibility and ensure biodegradability. Two polyurethanes based on L-tyrosine based diphenolic dipeptide, desaminotyrosyl tyrosine hexyl ester as chain extender are synthesized with polyethylene glycol (PEG) and polycaprolactone diol (PCL) as soft segment and hexamethylene diisocyanate as diisocyanate. The chemical structure and molecular characteristics of the polymers were studied by 1H NMR, FTIR, and gel permeation chromatography. Results of DSC and TGA analysis were used for examining the thermal behavior of the polyurethanes. In addition, DSC results were used to analyze the morphology of the polymers, which shows characteristic microphase behavior of the polyurethanes. The tensile properties of the polyurethanes are primarily controlled by the soft segment and are higher in PCL based polymers. Contact angle, water vapor permeation, release of model drug, and water absorption characteristics of the polymers were studied and analyzed in terms of structure of the polyurethanes. In vitro degradation studies show that PEG based polyurethane is more degradable than PCL based polyurethane. The difference in the soft segment structure offers significant variation in the properties of the polyurethanes. These polyurethanes show the potential for use in a variety of biomaterial applications including tissue engineering.     

Successful repair of a ventricular assist system percutaneous lead

A patient with an implanted, electrically powered, ventricular assist device (Thermo Cardiosystems VE HeartMate) experienced a partial break of the percutaneous lead 5 months after implantation. The break (limited to the Silicone rubber tube) occurred at the junction of the lead with the Y-connector to the controller and vent, leaving approximately 5 cm of exposed lead from the skin exit site to the connector. Electronic and pumping functions of the pump continued, but the opening in the lead (which went more that half way around the circumference) prevented the use of pneumatic actuation as a back-up mode for pump operation, and placed the pump at risk for contamination. Repair of the lead without surgical intervention was desirable, with ease of repair and minimal risk to the patient being the top priorities. The use of multiple layers of heat-shrink tubing or external metal stents was ruled out in favor of a three stage repair procedure. The first stage involved the removal of the Dacron velour in-growth material from the lead to expose the underlying Silicone rubber tube. While the opening in the tube was held shut, a coating of medical grade Silicone rubber adhesive was applied to the tube, then wrapped with a woven Dacron mesh, followed by two layers of plastic wrapping material to protect the adhesive. This initial layer was secured by an external stent of tubing with cable ties. After several days to allow for complete curing of the adhesive, the adhesive coating with mesh was repeated. The final step involved a double layer wrap of a 1 mm thick Silicone rubber sheeting with mesh incorporation and adhesive secured in place with cable ties. After completion of the repair and verification of the ability to operate the device with pneumatic actuation, the patient was discharged with no recurrence of the problem after 8 months of weekly follow-up. This experience demonstrates the need to clinically anticipate component repair or replacement without total device replacement in future implantable blood pump systems.     

Successful removal of an infected pacemaker lead using cardiopulmonary bypass in an 89-year-old patient

We report the case of an 89-year-old patient suffering from endocarditis with septicemia caused by a growth on a pacemaker lead. The entire pacemaker system was successfully removed using cardiopulmonary bypass. Although the patient was an octogenarian in poor condition with a systemic infection, an aggressive operation with careful perioperative management gave a good clinical result. As far as we know, this is the oldest patient in whom a pacemaker system has been removed using cardiopulmonary bypass.