Aerobic exercise improves depressive symptoms in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease.

Aerobic exercise has been shown to have established benefits on motor function in Parkinson's disease (PD). However, the impact of exercise on depressive symptoms in PD remains unclear. This study aimed to investigate the effects of regular exercise, specifically using a forced running wheel, on both motor performance and the prevalence of depression in a unilateral 6-OHDA-lesioned rat model of PD. The behavioral outcomes of exercise were assessed through the rotarod test (RT), forelimb adjusting step test (FAST), sucrose consumption test (SCT), and novelty sucrose splash test (NSST). Our data revealed evident depressive symptoms in the PD animals, characterized by reduced sucrose consumption in the SCT and diminished exploratory activity in the NSST compared to the naïve control group. Specifically, after 11 weeks of exercise, the PD exercise group demonstrated the most significant improvements in sucrose consumption in the SCT. Additionally, this group exhibited reduced immobility and increased exploratory behavior compared to the PD control group in the NSST. Furthermore, the PD exercise group displayed the greatest improvement in correcting forelimb stepping bias. Our results suggested that a regimen of running wheel exercise enhances motor abilities and mitigates the occurrence of depressive behaviors caused by 6-OHDA dopamine depletion in the PD rat model.

Perfusability and immunogenicity of implantable pre-vascularized tissues recapitulating features of native capillary network.

Vascularization is a key pre-requisite to engineered anatomical scale three dimensional (3-D) constructs to ensure their nutrient and oxygen supply upon implantation. Presently, engineered pre-vascularized 3-D tissues are limited to only micro-scale hydrogels, which meet neither the anatomical scale needs nor the complexity of natural extracellular matrix (ECM) environments. Anatomical scale perfusable constructs are critically needed for translational applications. To overcome this challenge, we previously developed pre-vascularized ECM sheets with long and oriented dense microvascular networks. The present study further evaluated the patency, perfusability and innate immune response toward these pre-vascularized constructs. Macrophage-co-cultured pre-vascularized constructs were evaluated in vitro to confirm micro-vessel patency and perturbations in macrophage metabolism. Subcutaneously implanted pre-vascularized constructs remained viable and formed a functional anastomosis with host vasculature within 3 days of implantation. This completely biological pre-vascularized construct holds great potential as a building block to engineer perfusable anatomical scale tissues.

Anti-Inflammatory and Anti-Thrombogenic Properties of Arterial Elastic Laminae.

Elastic laminae, an elastin-based, layered extracellular matrix structure in the media of arteries, can inhibit leukocyte adhesion and vascular smooth muscle cell proliferation and migration, exhibiting anti-inflammatory and anti-thrombogenic properties. These properties prevent inflammatory and thrombogenic activities in the arterial media, constituting a mechanism for the maintenance of the structural integrity of the arterial wall in vascular disorders. The biological basis for these properties is the elastin-induced activation of inhibitory signaling pathways, involving the inhibitory cell receptor signal regulatory protein α (SIRPα) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1). The activation of these molecules causes deactivation of cell adhesion- and proliferation-regulatory signaling mechanisms. Given such anti-inflammatory and anti-thrombogenic properties, elastic laminae and elastin-based materials have potential for use in vascular reconstruction.

An Assessment of Blood Vessel Remodeling of Nanofibrous Poly(ε-Caprolactone) Vascular Grafts in a Rat Animal Model.

The development of an ideal vascular prosthesis represents an important challenge in terms of the treatment of cardiovascular diseases with respect to which new materials are being considered that have produced promising results following testing in animal models. This study focuses on nanofibrous polycaprolactone-based grafts assessed by means of histological techniques 10 days and 6 months following suturing as a replacement for the rat aorta. A novel stereological approach for the assessment of cellular distribution within the graft thickness was developed. The cellularization of the thickness of the graft was found to be homogeneous after 10 days and to have changed after 6 months, at which time the majority of cells was discovered in the inner layer where the regeneration of the vessel wall was found to have occurred. Six months following implantation, the endothelialization of the graft lumen was complete, and no vasa vasorum were found to be present. Newly formed tissue resembling native elastic arteries with concentric layers composed of smooth muscle cells, collagen, and elastin was found in the implanted polycaprolactone-based grafts. Moreover, the inner layer of the graft was seen to have developed structural similarities to the regular aortic wall. The grafts appeared to be well tolerated, and no severe adverse reaction was recorded with the exception of one case of cartilaginous metaplasia close to the junctional suture.

Fibroblast-Generated Extracellular Matrix Guides Anastomosis during Wound Healing in an Engineered Lymphatic Skin Flap.

A healthy lymphatic system is required to return excess interstitial fluid back to the venous circulation. However, up to 49% of breast cancer survivors eventually develop breast cancer-related lymphedema due to lymphatic injuries from lymph node dissections or biopsies performed to treat cancer. While early-stage lymphedema can be ameliorated by manual lymph drainage, no cure exists for late-stage lymphedema when lymph vessels become completely dysfunctional. A viable late-stage treatment is the autotransplantation of functional lymphatic vessels. Here we report on a novel engineered lymphatic flap that may eventually replace the skin flaps used in vascularized lymph vessel transfers. The engineered flap mimics the lymphatic and dermal compartments of the skin by guiding multi-layered tissue organization of mesenchymal stem cells and lymphatic endothelial cells with an aligned decellularized fibroblast matrix. The construct was tested in a novel bilayered wound healing model and implanted into athymic nude rats. The in vitro model demonstrated capillary invasion into the wound gaps and deposition of extracellular matrix fibers, which may guide anastomosis and vascular integration of the graft during wound healing. The construct successfully anastomosed in vivo, forming chimeric vessels of human and rat cells. Overall, our flap replacement has high potential for treating lymphedema.

Enhancement of Lymphangiogenesis by Human Mesenchymal Stem Cell Sheet.

Preparation of human mesenchymal stem cell (hMSC) suspension for lymphedema treatment relies on conventional enzymatic digestion methods, which severely disrupts cell-cell and cell-extracellular matrix (ECM) connections, and drastically impairs cell retention and engraftment after transplantation. The objective of the present study is to evaluate the ability of hMSC-secreted ECM to augment lymphangiogenesis by using an in vitro coculturing model of hMSC sheets with lymphatic endothelial cells (LECs) and an in vivo mouse tail lymphedema model. Results demonstrate that the hMSC-secreted ECM augments the formation of lymphatic capillary-like structure by a factor of 1.2-3.6 relative to the hMSC control group, by serving as a prolymphangiogenic growth factor reservoir and facilitating cell regenerative activities. hMSC-derived ECM enhances MMP-2 mediated matrix remodeling, increases the synthesis of collagen IV and laminin, and promotes lymphatic microvessel-like structure formation. The injection of rat MSC sheet fragments into a mouse tail lymphedema model confirms the benefits of the hMSC-derived ECM by stimulating lymphangiogenesis and wound closure.

Improved biocompatibility of Zn-Ag-based stent materials by microstructure refinement.

The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here we investigate the biocompatibility of three Zn-based silver (Ag)-containing alloys, ranging from binary to quinary alloy systems. Selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. This experimental design was intended to clarify the relationship between elemental profile/microstructure and biocompatibility for the Zn-Ag system. We found that the quinary alloy system (Zn-4Ag-0.8Cu-0.6Mn-0.15Zr) performed significantly better, in terms of histomorphometry, than any alloy system we have evaluated to date. Furthermore, when solution treated to increase strength and ductility and reduce the fraction of Ag-rich phases, the quinary alloy's biocompatibility further improved. In vitro corrosion testing and metallographic analysis of in vivo implants demonstrated a more uniform mode of corrosion for the solution treated alloy. We conclude that Zn-Ag alloys can be engineered through alloying to substantially reduce neointimal growth. The positive effect on neointimal growth can be further enhanced by dissolving the AgZn3 precipitates in the Zn matrix to improve the corrosion uniformity. These findings demonstrate that neointimal-forming cells can be regulated by elemental additions and microstructural changes in degradable Zn-based implant materials. STATEMENT OF SIGNIFICANCE: The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here, selected binary and quinary Zn-Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. We found that applying a thermal treatment restores mechanical strength and mitigates the strain rate sensitivity of Zn-Ag alloys by dissolving AgZn3 precipitates. Ag-rich nano-precipitates in Zn decrease biocompatibility, a phenomenon that can be counteracted by dissolving the AgZn3 precipitates in the bulk Zn matrix.

In-vivo evaluation of molybdenum as bioabsorbable stent candidate.

Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo. The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material. Moreover, Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis. There was minimal neointimal hyperplasia over 6 months, an absence of excessive smooth muscle cell (SMC) proliferation or inflammation near the implant, and avoidance of significant harm to regenerating endothelial cells (EC). Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman's capsule and glomeruli, indicative of impaired filtering function and development of kidney disease, although quantifications of these morphological changes were not statistically significant. Together, the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells, while exerting potentially toxic effects in the kidneys that warrant further investigation.

In vitro behavior of bioactive hybrid implant composed of additively manufactured titanium alloy lattice infiltrated with Mg-based alloy.

We have developed a novel bioactive hybrid metallic implant that integrates the beneficial characteristics of a permanent matrix and a biodegradable substance. Such a combination may generate a material system that evolves into a porous structure within weeks to months following implantation and can be used to form strong interfacial bonding and osseointegration for orthopedic and dental applications. Presently, traditional technologies such as casting, powder metallurgy and plastic forming have limited ability to produce the complex bioactive implant structures that are required in practical applications. The present study aimed to develop an innovative bioactive TiMg (BTiMg) hybrid system using a Ti-lattice (Ti-6Al-4 V) produced by an additive manufacturing (AM) process, in combination with a new Mg-based alloy (Mg-2.4%Nd -0.6%Y -0.3%Zr) as a biodegradable filling material. We evaluated the in-vitro behavior of the BTiMg system in a simulated physiological environment, along with cytotoxicity assessment. The microstructure was evaluated by scanning electron microscopy and X-ray diffraction, mechanical properties were examined in terms of compressive strength, environmental performance analysis was conducted by electrochemical testing using potentiodynamic polarization and impedance spectroscopy (EIS), and cytotoxicity characteristics were assessed by indirect cell viability analysis. The results demonstrated the feasibility to produce geometrically complex implants by AM technology, as well as the strength and non-cytotoxic effects of the BTiMg system. Benefits included a relatively high ultimate compressive strength (UCS) and a high yield point (YP), along with an adequate cell viability response in the range between 70 and 120%.

Engineering the Lymphatic Network: A Solution to Lymphedema.

Secondary lymphedema is a life-long disorder characterized by chronic tissue swelling and inflammation that obstruct interstitial fluid circulation and immune cell trafficking. Regenerating lymphatic vasculatures using various strategies represents a promising treatment for lymphedema. Growth factor injection and gene delivery have been developed to stimulate lymphangiogenesis and augment interstitial fluid resorption. Using bioengineered materials as growth factor delivery vehicles allows for a more precisely targeted lymphangiogenic activation within the injured site. The implantation of prevascularized lymphatic tissue also promotes in situ lymphatic capillary network formation. The engineering of larger scale lymphatic tissues, including lymphatic collecting vessels and lymph nodes constructed by bioengineered scaffolds or decellularized animal tissues, offers alternatives to reconnecting damaged lymphatic vessels and restoring lymph circulation. These approaches provide lymphatic vascular grafting materials to reimpose lymphatic continuity across the site of injury, without creating secondary injuries at donor sites. The present work reviews molecular mechanisms mediating lymphatic system development, approaches to promoting lymphatic network regeneration, and strategies for engineering lymphatic tissues, including lymphatic capillaries, collecting vessels, and nodes. Challenges of advanced translational applications are also discussed.

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells.

Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc's differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants.

Zn2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants.

Biodegradable arterial implants based on zinc have been found to suppress neointimal hyperplasia, suggesting that biodegradable materials containing zinc may be used to construct vascular implants with a reduced rate of restenosis. However, the molecular mechanism has remained unclear. In this report, we show that zinc-containing materials can be used to prevent neointimal formation when implanted into the rat aorta. Indeed, neointimal cells were significantly more TUNEL positive and alpha-actin negative at the interface of biodegradable zinc vs. biostable platinum implants, in association with greater caspase-3 activity. Although zinc stimulated extensive neointimal smooth muscle cell (SMC) death, macrophage and proinflammatory markers CD68 and iNOS were not increased in neointimal tissue relative to biostable platinum control implants. Using arterial explants, ionic zinc was confirmed to promote SMC apoptosis by activating the caspase apoptotic signaling pathway. These observations suggest that zinc-containing materials can be used to construct vascular implants such as stents with reduced neointimal hyperplasia.

Comparison of optical microscopy and optical coherence tomography as quality assurance methods for evaluating lubricious hydrophilic coatings surrounding catheter shafts.

Cardiac catheters are a vital tool in medicine due to their widespread use in many minimally invasive procedures. To aid in advancing the catheter within the patient's vasculature, many catheters are coated with a lubricious hydrophilic coating (HPC). Although HPCs benefit patients, their delamination during use is a serious safety concern. Adverse health effects associated with HPC delamination include pulmonary and myocardial embolism, embolic stroke, infarction, and death. In order to improve patient outcomes, more consistent manufacturing methods and improved quality assurance techniques are needed to evaluate HPC medical devices. The present work investigates the efficacy of two novel methods to image and evaluate HPCs post-manufacturing, relative to industry-standard scanning electron microscopy (SEM)-based methods. We have shown that novel evaluation approaches based on optical microscopy (OM) and optical coherence tomography (OCT) are capable of imaging HPC layers and quantifying HPC thickness, saving hours of time relative to SEM sample preparation and imaging. Additionally, the nondestructive nature of OCT avoids damage and alteration to the HPC prior to imaging, leading to more reliable HPC thickness measurements. Overall, the work demonstrated the feasibility and advantages of using OM and OCT to image and measure HPC thickness relative to industry-standard SEM methods.

Towards revealing key factors in mechanical instability of bioabsorbable Zn-based alloys for intended vascular stenting.

Zn-based alloys are recognized as promising bioabsorbable materials for cardiovascular stents, due to their biocompatibility and favorable degradability as compared to Mg. However, both low strength and intrinsic mechanical instability arising from a strong strain rate sensitivity and strain softening behavior make development of Zn alloys challenging for stent applications. In this study, we developed binary Zn-4.0Ag and ternary Zn-4.0Ag-xMn (where x = 0.2-0.6wt%) alloys. An experimental methodology was designed by cold working followed by a thermal treatment on extruded alloys, through which the effects of the grain size and precipitates could be thoroughly investigated. Microstructural observations revealed a significant grain refinement during wire drawing, leading to an ultrafine-grained (UFG) structure with a size of 700 nm and 200 nm for the Zn-4.0Ag and Zn-4.0Ag-0.6Mn, respectively. Mn showed a powerful grain refining effect, as it promoted the dynamic recrystallization. Furthermore, cold working resulted in dynamic precipitation of AgZn3 particles, distributing throughout the Zn matrix. Such precipitates triggered mechanical degradation through an activation of Zn/AgZn3 boundary sliding, reducing the tensile strength by 74% and 57% for Zn-4.0Ag and Zn-4.0Ag-0.6Mn, respectively. The observed precipitation softening caused a strong strain rate sensitivity in cold drawn alloys. Short-time annealing significantly mitigated the mechanical instability by reducing the AgZn3 fraction. The ternary alloy wire showed superior microstructural stability relative to its Mn-free counterpart due to the pinning effect of Mn-rich particles on the grain boundaries. Eventually, a shift of the corrosion regime from localized to more uniform was observed after the heat treatment, mainly due to the dissolution of AgZn3 precipitates. STATEMENT OF SIGNIFICANCE: Owing to its promising biodegradability, zinc has been recognized as a potential biodegradable material for stenting applications. However, Zn's poor strength alongside intrinsic mechanical instability have propelled researchers to search for Zn alloys with improved mechanical properties. Although extensive researches have been conducted to satisfy the mentioned concerns, no Zn-based alloys with stabilized mechanical properties have yet been reported. In this work, the mechanical properties and stability of the Zn-Ag-based alloys were systematically evaluated as a function of microstructural features. We found that the microstructure design in Zn alloys can be used to find an effective strategy to not only improve the strength and suppress the mechanical instability but also to minimize any damage by augmenting the corrosion uniformity.

Analysis of vascular inflammation against bioresorbable Zn-Ag based alloys.

Zinc (Zn) has emerged as a promising bioresorbable stent material due to its satisfactory corrosion behavior and excellent biocompatibility. However, for load bearing implant applications, alloying is required to boost its mechanical properties as pure Zn exhibits poor strength. Unfortunately, an increase in inflammation relative to pure Zn is a commonly observed side-effect of Zn alloys. Consequently, the development of a Zn-based alloy that can simultaneously feature improved mechanical properties and suppress inflammatory responses is a big challenge. Here, a bioresorbable, biocompatible Zn-Ag-based quinary alloy was comprehensively evaluated in vivo, in comparison to reference materials. The inflammatory and smooth muscle cellular response was characterized and correlated to metrics of neointimal growth. We found that implantation of the quinary alloy was associated with significantly improved inflammatory activities relative to the reference materials. Additionally, we found that inflammation, but not smooth muscle cell hyperplasia, significantly correlates to neointimal growth for Zn alloys. The results suggest that inflammation is the main driver of neointimal growth for Zn-based alloys and that the quinary Zn-Ag-Mn-Zr-Cu alloy may impart inflammation-resistance properties to arterial implants.

In Vitro Corrosion and in Vivo Response to Zinc Implants with Electropolished and Anodized Surfaces.

Zinc (Zn)-based biodegradable metals have been widely investigated for cardiovascular stent and orthopedic applications. However, the effect of Zn surface features on adverse biological responses has not been well established. Here, we hypothesized that a metallic zinc implant's surface oxide film character may critically influence early neointimal growth and development. Electropolishing of surfaces has become the industry standard for metallic stents, while anodization of surfaces, although not practiced on stents at present, could increase the thickness of the stable oxide film and delay early-stage implant degradation. In this study, pure zinc samples were electropolished (EP) and anodized (AD) to engineer oxide films with distinctive physical and degradation characteristics, as determined by potentiodynamic polarization, electrochemical impedance spectroscopy, and static immersion tests. The samples were then implanted within the aortic lumen of adult Sprague-Dawley rats to determine the influence of surface engineering on biocompatibility responses to Zn implants. It was found that in vitro corrosion produced a porous corrosion layer for the EP samples and a densified layer on the AD samples. The AD material was more resistant to corrosion, while localized corrosion and pitting was seen on the EP surface. Interestingly, the increased variability from localized corrosion due to the surface film character translated directly to the in vivo performance, where 100% of the AD implants but only 44% of the EP implants met the biocompatibility benchmarks. Overall, the results suggest that oxide films on degradable zinc critically affect early neointimal progression and overall success of degradable Zn materials.

Magnetoelastic galfenol as a stent material for wirelessly controlled degradation rates.

The gold standard of care for coronary artery disease, a leading cause of death for in the world, is balloon angioplasty in conjunction with stent deployment. However, implantation injuries and long-term presence of foreign material often promotes significant luminal tissue growth, leading to a narrowing of the artery and severely restricted blood flow. A promising method to mitigate this process is the use of biodegradable metallic stents, but thus far they have either degraded too slowly (iron) or disappeared prematurely (magnesium). The present work investigates the use of a unique type of magnetic material, galfenol (iron-gallium), for postoperative wireless control of stent degradation rates. Due to its magnetoelastic property, galfenol experiences longitudinal micron-level elongations when exposed to applied magnetic fields, allowing generation of a microstirring effect that affect its degradation behavior. In vitro indirect cytotoxicity tests on primary rat aortic smooth muscle cells indicated that galfenol byproducts must be concentrated approximately seven times from collected 60 day degradation medium to cause ∼15% of death from all cells. Surface and cross-sectional characterization of the material indicate that galfenol (Fe80 Ga20 ) degradation rates (∼0.55% per month) are insufficient for stenting applications. While this material may not be ideal for comprising the entire stent, there is potential for use in combination with other materials. Furthermore, the ability to control degradation rates postimplantation opens new possibilities for biodegradable stents; additional magnetoelastic materials should be investigated for use in stenting applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 232-241, 2019.

Preclinical In-Vivo Evaluation and Screening of Zinc Based Degradable Metals for Endovascular Stents.

Zinc alloy development and characterization for vascular stent application has been facilitated by many standardized and inexpensive methods. In contrast, overly simplistic in vitro approaches dominate the preliminary biological testing of materials. In 2012, our group introduced a metal wire implantation model in rats as a cost effective and realistic approach for the biocompatibility evaluation of degradable materials in the vascular environment. Here, we have adapted metrics routinely used for evaluating stents to quantitatively characterize the long-term progression of the neointima that forms around zinc based wire implants. Histological cross-sections were used to measure the length of neointimal protrusion from the wire into the lumen (denoted wire to lumen thickness), the base neointimal length (describing the breadth of neointimal activation), and the neointimal area. These metrics were used to provide in depth characterization details for neointimal responses to Zn-Mg and Zn-Li alloys and may be used to compare different materials.

Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.

Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin.

Novel high-strength, low-alloys Zn-Mg (<0.1wt% Mg) and their arterial biodegradation.

It is still an open challenge to find a biodegradable metallic material exhibiting sufficient mechanical properties and degradation behavior to serve as an arterial stent. In this study, Zn-Mg alloys of 0.002 (Zn-002Mg), 0.005 (Zn-005Mg) and 0.08wt% Mg (Zn-08Mg) content were cast, extruded and drawn to 0.25mm diameter, and evaluated as potential biodegradable stent materials. Structural analysis confirmed formation of Mg2Zn11 intermetallic in all three alloys with the average grain size decreasing with increasing Mg content. Tensile testing, fractography analysis and micro hardness measurements showed the best integration of strength, ductility and hardness for the Zn-08Mg alloy. Yield strength, tensile strength, and elongation to failure values of >200-300MPa, >300-400MPa, and >30% respectively, were recorded for Zn-08Mg. This metal appears to be the first formulated biodegradable material that satisfies benchmark values desirable for endovascular stenting. Unfortunately, the alloy reveals signs of age hardening and strain rate sensitivity, which need to be addressed before using this metal for stenting. The explants of Zn-08Mg alloy residing in the abdominal aorta of adult male Sprague-Dawley rats for 1.5, 3, 4.5, 6 and 11months demonstrated similar, yet slightly elevated inflammation and neointimal activation for the alloy relative to what was recently reported for pure zinc.