New biodegradable small-diameter artificial vascular prosthesis: a feasibility study

An in-house built instrument was used to fabricate a small internal diameter (2 mm) artificial vascular prosthesis from biodegradable chitosan. This new artificial vascular prosthesis has shown a good biocompatibility based on the studies of its cell compatibility, inflammatory reaction, and platelet adhesion. In an animal test, the prosthesis was used to replace a 4-cm-long section of femoral artery in each of the seven tested dogs. The patency of the replacement was monitored at regular intervals using Doppler ultrasound diagnostics. Nine months after the implantation, hematoxylin and eosin staining, immunohistochemical study, and scanning electron microscope observation were carried out. Complete decomposition of the prosthesis and replacement by a natural blood vessel were observed. The results suggests that the artificial vascular prosthesis displays many characteristics of the "ideal" small-diameter artificial vascular, and have the biocompatibility that can be tailored to match those desired in vascular replacement application.     

Coaxial double-tubular compliant arterial graft prosthesis: time-dependent morphogenesis and compliance changes after implantation

In order to reduce the compliance mismatch between the native artery and the artificial graft, we have developed a coaxial double-tubular compliant graft, using multiply micropored segmented polyurethane (SPU) thin films, which mimics the relationship between the intraluminal pressure and vessel internal diameter (P-D) of the native artery (termed "J" curve). The graft was coaxially assembled by inserting a high-compliance inner tube with a heparin-immobilized photocured gelatin coating layer into a low-compliance outer tube with a photocured hydrophilic polymer coating layer. Twenty-eight coaxial double-tubular compliant grafts were implanted into the canine common carotid arteries in an end-to-end fashion for up to 12 months. The overall patency rate was 86% (24/28), and neither rupture nor aneurysmal formation was observed. A neoarterial wall was formed via transanastomotic and transmural tissue ingrowth, resulting in neoarterial tissue formation on the luminal surface and into the intertubular space of the double-tubular graft, accompanied by mainly myofibroblasts and inflammatory cells in the early stage and endothelialization and collagen-rich extracellular matrices in the late stage of implantation. Surrounding-tissue adhesion with the outer tube was prevented by the hydrophilic polymer coating. Although the J curve of the implanted prototype model was preserved 1 month after implantation, the impaired J curves were observed because of tissue ingrowth and tissue adhesion between the outer surface of the inner tube and the surrounding tissues 3 and 6 months after implantation. At 12 months after implantation, however, the implanted coaxial double-tubular graft exhibited high compliance due to biodegradation of the SPU films.     

In vivo resorption of a biodegradable polyurethane foam, based on 1,4-butanediisocyanate: a three-year subcutaneous implantation study

Degradable polyurethanes (PUs), based on aliphatic diisocyanates, can be very useful in tissue regeneration applications. Their long-term in vivo degradation has not been extensively investigated. In this study a biodegradable PU with copolyester soft segments of DL-lactide/epsilon-caprolactone and hard segments synthesized from 1,4-butanediisocyanate was evaluated with regard to tissue response during degradation and, ultimately, the resorption of the material. Highly porous PU foam discs were subcutaneously implanted in rats and rabbits for intervals up to 3 years. A copolymer foam of DL-lactide and epsilon-caprolactone served as a control. The foams, the surrounding tissues and the draining lymph nodes were evaluated with light and electron microscopy. In the first stages of degradation the number of macrophages and giant cells increased. As the resorption stage set in their numbers gradually decreased. Electron microscopy showed macrophages containing pieces of PU. The size of the intracellular PU particles diminished and cells containing these remnants gradually disappeared after periods from 1 to 3 years. After 3 years an occasional, isolated macrophage with biomaterial remnants could be traced in both PU and copolymer explants. Single macrophages with biomaterial remnants were observed in the lymph nodes between 39 weeks and 1.5 years following implantation. It is concluded that the PU foam is biocompatible during degradation. After 3 years PU samples had been resorbed almost completely. These results indicate that the PU foam can be safely used as a biodegradable implant.     

Jaundice and wound healing: a tissue-culture study.

The effects of jaundice on wound healing have been studied by growing fibroblasts, in vitro, in normal culture media, in culture media to which bilirubin has been added, and in culture media containing sera from jaundiced patients. It has been found that the addition of bilirubin to the culture media causes morphological changes in the fibroblasts, and impairs the growth of cells. The addition of jaundiced human sera to the culture also causes similar changes.     

An arterial prosthesis from Argentina: the Barone Microvelour arterial graft

The manufacture of a polyester vascular prosthesis in the southern hemisphere is a new development in the global dissemination of this maturing technology. Hence the recent introduction of the Barone Microvelour arterial graft from Argentina has highlighted the need for a comparative in vitro and in vivo study to compare its structure and performance with that of existing commercial products. Following a series of laboratory tests and implantations as a thoracoabdominal bypass in dogs, the Barone Microvelour has been identified as a strong graft constructed after the style of early weft-knitted designs. It provides an equivalent sequence and rate of healing to that of other polyester knitted grafts.     

Cervical spine biomechanics following implantation of a disc prosthesis

This study presents a finite element model of the C4-C7 segment in healthy conditions and after implantation of a disc prosthesis at a single level, in order to investigate of the influence of disc arthroplasty on the biomechanics of the cervical spine. A nonlinear finite element model of the C4-C7 segment in intact conditions was developed and run in flexion and extension. A detailed model of the Bryan disc prosthesis, including contacts between the different components of the device, was built and positioned at C5-C6. The calculated segmental motion resulted preserved after disc arthroplasty, with respect to the model of the intact spine, in both flexion and extension. A general preservation of the forces transmitted through the facet joints was obtained; a minor force increase at the implanted level was detected. The analysis of the instantaneous centers of rotation (ICR) in flexion-extension showed the preservation of a physiological kinematics. The mechanical behaviour showed an asymmetry between flexion and extension, probably due to the removal of the anterior longitudinal ligament and the anterior part of the annulus fibrosus, and the preservation of the posterior structures. In general, the disc prosthesis showed to be able to reproduce a nearly physiological motion. However, other important mechanical aspects, such as the possible micromotion at the bone-implant interface and the possible degenerative conditions of the spine, need to be evaluated before drawing a conclusion about total disc arthroplasty from an engineering point of view.     

A biodegradable vascularizing membrane: a feasibility study

Regenerative medicine and in vivo biosensor applications require the formation of mature vascular networks for long-term success. This study investigated whether biodegradable porous membranes could induce the formation of a vascularized fibrous capsule and, if so, the effect of degradation kinetics on neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic) acid (PLGA) membranes were created by a solvent casting/salt leaching method. Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary degradation kinetics. The membranes were designed to have an average 60mum pore diameter, as this pore size has been shown to be optimal for inducing blood vessel formation around nondegradable polymer materials. Membrane samples were imaged by scanning electron microscopy at several time points during in vitro degradation to assess any changes in pore structure. The in vivo performance of the membranes was assessed in Sprague-Dawley rats by measuring vascularization within the fibrous capsule that forms adjacent to implants. The vascular density within 100microm of the membranes was compared with that seen in normal tissue, and to that surrounding the commercially available vascularizing membrane TheraCyte. The hemoglobin content of tissue containing the membranes was measured by four-dimensional elastic light scattering as a novel method to assess tissue perfusion. Results from this study show that slow-degrading membranes induce greater amounts of neovascularization and a thinner fibrous capsule relative to fast degrading membranes. These results may be due both to an initially increased number of macrophages surrounding the slower degrading membranes and to the maintenance of their initial pore structure.     

Mechanical mitral prosthesis with a short-term left ventricular assist device

Mechanical circulatory support with ventricular assist devices in patients with mechanical valvular prostheses may predispose to thromboembolic and hemodynamic complications. Conventional approaches to reduce these risks involve redo valve replacement to a bioprosthesis. Careful management of the ventricular assist device to allow flow across the prosthesis may obviate the need for redo valve replacement. Avoidance of further myocardial ischemia during redo valve replacement carries particular importance for patients in whom the aim is recovery. We report a successful outcome from retention of a mechanical mitral prosthesis during a 10-day period of mechanical circulatory support and review the pertinent literature.     

Toxicity test of biodegradable polymers by implantation in rabbit cornea.

To evaluate whether or not the corneal micropocket implantation is effective for determining the toxicity of polymeric materials, currently used biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), LA-GA copolymers, and three kinds of poly(2-cyano-acrylate)s (PCA) were implanted in a rabbit corneal pouch and the tissue responses were observed macroscopically and microscopically. It was found that PLA induced no vascularization, whereas a residual solvent and ethylene oxide gas remaining in the PLA matrix invoked vascularization. Vascularization clearly took place when PGA was implanted in the cornea, which became opaque, probably because of cellular infiltration. In the case of PCA implantation, severe inflammation as well as vascular invasion occurred in the initial stage. It is likely that these tissue reactions were caused by the leachables from the implanted materials, the extent being dependent on the leaching rate and the toxicity. It was concluded that the corneal micropocket assay is a good means to detect trace amounts of leachables from implanted materials without sacrificing the animals with the implanted materials.     

Dynamics of wound healing after silicone device implantation.

A large surgical wound is required for implantation of silicone mammary devices. Formation of capsules around silicone devices follows wound healing processes except that the healing is conformed and significantly delayed by the physical presence of the implant. Multilayered capsules are thicker and lymphocytic and plasmalymphocytic vasculitis, markers for delayed hypersensitivity, also correlate with thicker capsules. Polyurethane-coated devices induce very thick capsules that remain so for over 20 years. By contrast, gel and saline content devices show maximum thickness at 6. 5 years. Active T(H) lymphocyte memory does not differ by implant type for individuals with devices in place and that for gel content devices peaks at 10.5 years. There was a significant decrease in T cell indexes only after the removal of saline content devices. Comparison of the rate of formation of the periprosthetic capsule with the healing time of large wounds of similar size indicates that silicone devices interfere with the healing process, requiring substantially more time. This extended period has the potential for enhancing autoimmune conversion as a consequence of persistent delayed hypersensitivity.     

Prefabricated tracheal prosthesis with partial biodegradable materials: a surgical and tissue engineering evaluation in vivo

Large and circumferential tracheal defects remain at this time an unsolved problem for reconstructive surgery. Many types of prosthetic and tissue grafts have been used but with limited comfortable results. Major complications are anastomotic dehiscence, graft ischemia and stenosis due to the poor vascularization of the prosthetic complex. We studied the in vivo behaviour of a prefabricated flap composed of a partially bioresorbable tracheal prosthesis and an arterio-venous vascular carrier. The prosthesis was made of a tubular skeleton of knitted Dacron (20 microm porosity) embedded within a bioresorbable poly-lactic-co-glycolic acid polymer (PLA(75)GA(25)) covering both sides. Fifteen New Zealand White rabbits were divided in three groups, depending on the time of examination (30, 90 and 180 days post-implantation). The prosthesis was implanted in the visceral space of the neck using the common carotid trunk and the internal jugular vein as vascular pedicle. The histological, immunohistochemical, and ESEM analyses of collected samples, showed a time-dependent process of tissue neoformation and neovascularization on the prosthetic material with a significant increase from 30 to 90 days post-implantation. In contrast, there was no statistically significant difference in the fibrovascular connective deposition from 90 to 180 days. This finding indicated the three months time as the best period for the tissue deposition and consequent hypothetical orthotopic transplantation of the prosthesis. Further in vivo studies are intended to confirm the results.     

Development of a biodegradable foam for use in negative pressure wound therapy

Treatment of wounds using negative pressure wound therapy (NPWT) uses a nondegradable polyvinyl alcohol (PVA) foam in the application of negative pressures typically for 1-3 days. The purpose of this study was to construct and test biodegradable poly(ε-caprolactone) (PCL) foam as a substitute for the PVA foam. Such a foam would be left within the wound until healing was achieved and form a biodegradable matrix into which tissue would grow. The use of such foam would obviate the need for any serial foam changes and a final foam removal, thus making patient care much easier and more economical. PCL foams were prepared by salt leaching and phase separation. Morphological and mechanical properties of the foams were characterized and compared to PVA foam. PCL and PVA foams were tested on the uncut surface of a pig liver maintained in a hydration chamber continuously replenished with saline under the conditions of negative pressure of 50 mm Hg for 72 h. The results demonstrated that PCL foam made from phase separation had the similar properties and function as the PVA foam. The results demonstrate that PCL foam is an appropriate substitute for currently used nondegradable PVA foam in NPWT applications.     

A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients.

A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients has been developed at the University of Melbourne. It has been designed as a multiple-electrode implant to provide the best chance of enabling patients to understand speech. It has been shown that an electrode array can be threaded along the coills of the inner ear close to residual auditory nerves. Experimental studies have indicated that the long-term implantation of the array will not lead to significant degeneration of auditory nerve fibres. Loss of platinum from the stimulating electrodes can be minimized with a biphasic constant current pulse, where the first phase is negative with respect to ground. The receiver-stimulator component has also been designed to provide 10-15 channels of stimulation. Furthermore, the phase and amplitude of the stimuli to individual electrodes can be varied to enable the localization of the electrical fields to discrete groups of nerve fibres, and the correct method of frequency and intensity coding to be determined. Finally, the device should be used in the first instance for a specially selected group of adults who are post-lingually deaf.     

Improving arterial prosthesis neo-endothelialization: application of a proactive VEGF construct onto PTFE surfaces

The formation of a confluent endothelium on expanded polytetrafluoroethylene (PTFE) vascular prostheses has never been observed. This lack of endothelialization is known to be one of the main reasons leading to the development of thromboses and/or intimal hyperplasia. In this context, several efforts were put forward to promote endothelial cell coverage on the internal surface of synthetic vascular prostheses. The goal of the present study was to immobilize the vascular endothelial growth factor (VEGF) onto Teflon PTFE surfaces to generate a proactive polymer construct favoring interaction with endothelial cells. An ammonia plasma treatment was first used to graft amino groups on PTFE films. Subsequent reactions were performed to covalently bind human serum albumin (HSA) on the polymer surface and to load this protein with negative charges, which allows adsorbtion of VEGF onto HSA via strong electrostatic interactions. X-ray photoelectron spectroscopy (XPS) experiments along with surface derivatization strategies were performed between each synthesis step to ascertain the occurrence of the various molecules surface immobilization. Finally, the electrostatic binding of VEGF to the negatively charged HSA matrix was performed and validated by ELISA. Endothelial cell adhesion and migration experiments were carried out to validate the potential of this VEGF-containing biological construct to act as a proactive media toward the development of endothelial cells.     

Modern wound dressings: a systematic approach to wound healing.

The advent of modern wound care management constitutes one of the most innovative applications of medical device technology. The foundation for wound care recent advances has been built upon the developments achieved in polymer technology over the last three decades. New and unique materials have been engineered to provide properties with significant technical and clinical benefits. These new wound care products were made possible by the convergence of three interrelated disciplines: (1) more complete understanding of the underlying principles of dermal wound healing processes, (2) new elastomeric polymers capable of being fabricated into protective dressings, and (3) advances in breathable adhesive technology. The following discussion provides a critical review of the current status of technology and the worldwide opportunities for improved wound management products. Particular attention is focused on the clinical applications of the newer, breathable dressing products, which approximate a temporary synthetic artificial skin.     

Introducing abortion patients to a culture of support: a pilot study

Currently in the United States, women who have abortions face a societal culture in which disapproval, stigma, and misinformation about the risks and sequelae of abortion are common. The purpose of this study is to pilot test an intervention that introduces abortion patients to a “culture of support” by providing validating messages and information about groups and services that support women in their reproductive decisions, addressing stigma, and providing information to help women identify and avoid sources of abortion misinformation. Twenty-two women who completed their post-operative exam after abortion were enrolled to take part in the study intervention. In-depth interviews were conducted to explore patient experiences and responses to the intervention. All (22/22) participants responded that they believed that interventions like the one studied could help women avoid letting the judgmental actions and attitudes of others “get to them so much”. All (20/20) participants felt that the intervention was personally helpful to them. An intervention that introduces women having abortions to a “culture of support” was well-received. This study provides a framework for future research about the content, strength, and effect of societal and cultural influences on women having abortions and for additional research about interventions to promote resilience after abortion.     

国产可降解雷帕霉素药物洗脱支架置入的疗效评价：与金属裸支架比较

背景：药物洗脱支架明显降低了再狭窄率,但永久聚合物涂层在抑制血管平滑肌细胞增生的同时,阻碍血管完全内皮化进程,促使再狭窄发生,且永久聚合物涂层可引发晚期血栓等并发症。 目的：观察冠心病合并糖尿患者置入国产可降解药物洗脱支架后的远期疗效和安全性,并与置入金属裸支架患者进行比较。 方法：实验组选择冠心病合并2型糖尿病患者136例,首次经皮冠状动脉成形治疗,置入国产可降解药物洗脱支架(EXCELTM),并以同期行金属裸支架置入治疗的冠心病合并2型糖尿病患者87例为对照组,随访12个月以上,记录主要不良心血管事件发生情况,并复查冠状动脉造影。 结果与结论：实验组129例,对照组83例完成(13.5±3.5)个月随访,实验组及对照组分别有8例及12例患者发生不良心血管事件,两组间差异有显著性意义(P=0.045),对照组靶血管血运重建及再发心绞痛多于实验组(P < 0.05)。两组患者随访冠状动脉造影的定量分析提示实验组最终丢失指数小于对照组(P < 0.05),再狭窄率低于对照组(P < 0.05)。说明对于冠心病合并糖尿病患者,应用国产可降解药物洗脱支架可降低不良心血管事件发生率,减少再狭窄,改善患者远期预后,安全性能良好。     

Repopulation of guinea-pig skin by melanocytes during wound healing: a morphometric study.

Epidermal keratinocytes and melanocytes have a close functional interrelationship. In order to study this relationship we used computer-assisted three-dimensional morphometry (CAM) to investigate the shape and size changes of the cutaneous melanocyte in healing guinea-pig skin. The combination of CAM with osmium iodide staining and resin embedding of tissue gave excellent results and allowed qualitative and quantitative morphometric assessment of melanocytes in vertical epidermal sections. The changes in melanocytes and keratinocytes during healing of a standard 1 cm full thickness wound in the guinea-pig were studied. After an initial decrease, more melanocytes per mm2 of epidermis were seen (from 36 days). These were smaller in volume with shorter, less branched dendrites compared to controls. An unexpected finding was a late phase of melanocyte proliferation, at the end of our study period (99 days). Clearly, the complex changes in the melanocyte-keratinocyte relationship during wound healing continue throughout and beyond the period of our study.     

In vivo biocompatibility and degradation studies of polyhydroxyoctanoate in the rat: a new sealant for the polyester arterial prosthesis.

The present study examined the biocompatibility and degradation properties of poly (beta-hydroxy octanoate) (PHO) as an impregnation substrate on arterial prostheses. PHO-impregnated polyester grafts sterilized by ethylene oxide (EO) or gamma (gamma) radiation, and polyester Dacron(R) prostheses impregnated with fluoropolymer, gelatin, or albumin were implanted subcutaneously in rats for periods ranging from 2 to 180 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion while performing histological studies at the tissue/prosthesis interface. The degradation was determined by chemical analysis of the EO and gamma-sterilized PHO after implantation using differential scanning calorimetry (DSC), wide angle x-ray diffraction (WAXD), and size exclusion chromatography (SEC). Alkaline phosphatase activity by the sterilized PHO and by the gelatin and albumin grafts was significantly elevated early after implantation in contrast to that of the Dacron and fluoropolymer grafts that occurred later, at 7 and 5 days, respectively The peak of acid phosphatase activity for all of the grafts occurred between 5 and 10 days postimplantation, with the gamma-sterilized PHO grafts recording the greatest activity. Histological study revealed that the tissue incorporation into the graft wall was earlier and more complete for the Dacron and fluoropolymer grafts after 6 months than for the gelatin and albumin grafts, because the latter induced important inflammatory reactions during the resorption of the cross-linked protein substrates. The EO and gamma-sterilized PHO grafts exhibited a similar healing sequence characterized by the development of a collagenous tissue surrounding the prostheses. However, no infiltration of tissue into the graft wall was observed after 6 months, mainly because of the presence of the PHO. Degradation of the EO and gamma-sterilized PHO occurred preferentially by a hydrolytic mechanism as shown by a 30% molecular weight decrease after 6 months. In conclusion, PHO showed good biocompatibility in terms of enzyme activity and tissue reaction. Degradation was a slow, in vivo process controlled primarily by a random hydrolytic reaction and by a local enzymatic attack by macrophages and giant cells.