Vascular Transplantation Research Articles

Outcomes and Incidence of Vascular Complications Postmultivisceral Transplant

Outcomes and Incidence of Vascular Complications Postmultivisceral Transplant

Anti-thrombotic poly(AAm-co-NaAMPS)-xanthan hydrogel-expanded polytetrafluoroethylene (ePTFE) vascular grafts with enhanced endothelialization and hemocompatibility properties

Cardiovascular diseases (CVDs) are the leading cause of death among all non-communicable diseases globally. Although expanded polytetrafluoroethylene (ePTFE) has been widely used for larger-diameter vascular graft transplantation, the persistent thrombus formation and intimal hyperplasia of small-diameter vascular grafts (SDVGs) made of ePTFE to treat severe CVDs remain the biggest challenges due to lack of biocompatibility and endothelium. In this study, bi-layered poly(acrylamide-co-2-Acrylamido-2-methyl-1-propanesulfonic acid sodium)-xanthan hydrogel-ePTFE (poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE) vascular grafts capable of promoting endothelialization and prohibiting thrombosis were synthesized and fabricated. While the external ePTFE layer of the vascular grafts provided the mechanical stability, the inner hydrogel layer offered much-needed cytocompatibility, hemocompatibility, and endothelialization functions. The interface morphology between the inner hydrogel layer and the outer ePTFE layer was observed by scanning electron microscope (SEM), which revealed that the hydrogel was well attached to the porous ePTFE through mechanical interlocking. Among all the hydrogel compositions tested with cell culture using human umbilical vein endothelial cells (HUVECs), the hydrogel with the molar ratio of 40:60 (NaAMPS/AAm) composition (i.e., Hydrogel 40:60) exhibited the best endothelialization function, as it produced the largest endothelialization area that was three times more than of that of plain ePTFE on day 14, maintained the highest average cell viability, and had the best cell morphology. Hydrogel 40:60 also showed excellent hemocompatibility, prolonged activated partial thromboplastin time (aPTT), and good mechanical properties. Overall, bi-layered poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE vascular grafts with the Hydrogel 40:60 composition could potentially solve the critical challenge of thrombus formation in vascular graft transplantation applications.

Successful repair of transplant renal artery aneurysm (TRAA)

BackgroundTransplant renal artery aneurysm (TRAA) is rare. TRAA that develops post transplantation consists of 0.10% of the vascular complications post renal transplant (Transplant Proc 41:1609-1614, 2009; Indian J Urol 29:42-47, 2013).Case presentationWe report a case of TRAA in an asymptomatic young female. CT angiogram with detailed 3D reconstruction showed a 2.6 × 2.2 cm wide neck saccular TRAA arising from the anterior segmental branch of the graft renal artery (Figs. 2 and 3). A multidisciplinary team of interventional radiologists, vascular and urologist was involved for preoperative surgical planning and unique repair methods. Endovascular and percutaneous approaches were deemed not feasible, and an open in vivo approach with a saphenous vein graft was taken.ConclusionTRAA, albeit rare, is a complication that can occur post renal transplant. In-vivo surgical repair of TRAA is feasible with a multidisciplinary approach and careful preoperative planning. Saphenous vein graft is still a versatile graft and can be used as a conduit successfully.

Human Tracheal Transplantation.

Long-segment tracheal airway defects may be congenital or result from burns, trauma, iatrogenic intubation damage, or tumor invasion. Although airway defects <6 cm in length may be reconstructed using existing end-to-end reconstructive techniques, defects >6 cm continue to challenge surgeons worldwide. The reconstruction of long-segment tracheal defects has long been a reconstructive dilemma, and these defects are associated with significant morbidity and mortality. Many of these defects are not compatible with life or require a permanent extended-length tracheostomy that is fraught with complications including mucus plugging and tracheoesophageal fistula. Extensive circumferential tracheal defects require a reconstructive technique that provides a rigid structure able to withstand the inspiratory pressures, a structure that will biologically integrate, and contain functional ciliated epithelium to allow for normal mucociliary clearance. Tracheal transplantation has been considered the reconstructive "Holy Grail;" however, there has been a long-held scientific dogma that revascularization of the trachea was not possible. This dogma stifled research to achieve single-staged vascularized tracheal transplantation and prompted the introduction of many creative and inventive alternatives. Throughout history, alloplastic material, nonvascularized allografts, and homografts have been used to address this dilemma. However, these techniques have largely been unsuccessful. The recent introduction of a technique for single-staged vascularized tracheal transplantation may offer a solution to this dilemma and potentially a solution to management of the fatal tracheoesophageal fistula.

The Influence of Textile Structure Characteristics on the Performance of Artificial Blood Vessels.

Cardiovascular disease is a major threat to human health worldwide, and vascular transplantation surgery is a treatment method for this disease. Often, autologous blood vessels cannot meet the needs of surgery. However, allogeneic blood vessels have limited availability or may cause rejection reactions. Therefore, the development of biocompatible artificial blood vessels is needed to solve the problem of donor shortage. Tubular fabrics prepared by textile structures have flexible compliance, which cannot be matched by other structural blood vessels. Therefore, biomedical artificial blood vessels have been widely studied in recent decades up to the present. This article focuses on reviewing four textile methods used, at present, in the manufacture of artificial blood vessels: knitting, weaving, braiding, and electrospinning. The article mainly introduces the particular effects of different structural characteristics possessed by various textile methods on the production of artificial blood vessels, such as compliance, mechanical properties, and pore size. It was concluded that woven blood vessels possess superior mechanical properties and dimensional stability, while the knitted fabrication method facilitates excellent compliance, elasticity, and porosity of blood vessels. Additionally, the study prominently showcases the ease of rebound and compression of braided tubes, as well as the significant biological benefits of electrospinning. Moreover, moderate porosity and good mechanical strength can be achieved by changing the original structural parameters; increasing the floating warp, enlarging the braiding angle, and reducing the fiber fineness and diameter can achieve greater compliance. Furthermore, physical, chemical, or biological methods can be used to further improve the biocompatibility, antibacterial, anti-inflammatory, and endothelialization of blood vessels, thereby improving their functionality. The aim is to provide some guidance for the further development of artificial blood vessels.

Biomimetic Antithrombotic Tissue-Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Here, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.

Sulfasalazine induces autophagy inhibiting neointimal hyperplasia following carotid artery injuries in mice.

Background: Neointimal hyperplasia (NH) is a crucial pathophysiological feature in vascular transplant and in-stent restenosis. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in neointimal hyperplasia. This study aims to explore the potentialities and mechanism of sulfasalazine (SSZ) in the prevention of restenosis. Methods: Sulfasalazine was encapsulated in nanoparticles made of poly (lactic-co-glycolic acid) (PLGA). In vivo, carotid ligation injury was induced in mice to induce Neointimal hyperplasia, with or without sulfasalazine containing nanoparticles (NP-SSZ) treatment. After 4weeks, the arteries were collected for histology, immunofluorescence, Western blotting (WB) and qRT-PCR. In vitro, vascular smooth muscle cells were treated with TNF-α to induce cell proliferation and migration, followed by SSZ or vehicle treatment. WB was performed to further explore its mechanism. Results: The ratio of intima to media thickness (I/M) was increased after ligation injury on day 28, while the ratio was significantly reduced in the NP-SSZ treatment group. The dual positive nuclei of Ki-67 and α-SMA were 47.83% ± 9.15%, whereas only 29.83% ± 5.98% in the NP-SSZ-treated group (p < 0.05). Both MMP-2 and MMP-9 were decreased in the NP-SSZ treatment group (p < 0.05, p < 0.05, respectively) compared to the control group. The levels of the targeted inflammatory genes (TNF-α, VCAM-1, ICAM-1, MCP-1) were lower in the NP-SSZ treatment group compared with the control group. In vitro, the proliferating cell nuclear antigen (PCNA) expression was significantly decreased in the SSZ treatment group. The cell viability of VSMCs was markedly increased in the TNF-α treatment group, whereas sulfasalazine treatment inhibited this effect. LC3 II and P62 protein expression were higher in the SSZ group than in the vehicle group both in vitro and in vivo. The phosphorylation of NF-kB (p-NF-kB) and the phosphorylation of mTOR (p-mTOR) were decreased in the TNF-α+ SSZ group, whereas the P62 and LC3 II expression levels were increased. However, the expression level of p-mTOR, P62, and LC3 II was reversed after co-treatment with the agonist of mTOR MHY1485, whereas the p-NF-kB expression level was unchanged. Conclusion: sulfasalazine inhibited vascular smooth muscle cells proliferation and migration in vitro and Neointimal hyperplasia in vivo through NF-kB/mTOR-mediated autophagy.

Reply to "Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome".

We thank Agrawal et al for their interest in our recent publication1 in the Transplantation journal; we agree with them that there are still many questions, much more than the ones pointed out in this letter, to be answered in relation to porto-sinusoidal vascular liver disorder (PSVD) and liver transplant (LT). However, we would like to emphasize that it is clearly stated in our article that the aim of our study was to identify features associated with post-LT outcome in, up to now, the largest group of PSVD patients, focusing on potential recurrence of the disease and post-LT survival.1 Therefore, answering the points mentioned by Agrawal et al was completely out of the scope of our article. Indeed, we are now evaluating the natural history of a large cohort of PSVD patients, trying to answer points raised by Agrawal et al, and also evaluating many other aspects of the disease. We completely agree with Agrawal et al about the relevance of one very important message of our work. There is a subgroup of PSVD patients who have quite high mortality despite LT, and in most of these cases, death is more related to the underlying associated disorder than to the liver disease itself. Therefore, when considering LT in this subgroup of PSVD patients, the potential risk and benefit of being transplanted must be discussed in an individualized way.

A Biomimetic Approach Utilizing Pulsatile Perfusion Generates Contractile Vascular Grafts.

Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ cardiovascular progenitor cells (CPCs) have demonstrated the capacity for differentiation into all cell types of the heart and outflow tracts. We hypothesize that CPC seeding of decellularized pulmonary arteries and bioreactor culture under physiologic flow conditions will drive vascular differentiation of CPCs and result in a conduit more suitable for implantation and long-term growth. We began by decellularizing ovine pulmonary arteries and characterizing the composition of the extracellular matrix (ECM). Hemodynamic testing of decellularized vessels in a custom bioreactor was used to define the scaffold mechanical properties over a range of pressures and flow rates. Next, our expanded ovine CPCs were suspended in growth media and injected intramurally into decellularized pulmonary arteries that were subsequently cultured in either static or pulsatile cultures. A combination of immunohistochemistry, real-time polymerase chain reaction (PCR), and tissue bath contraction studies were used to evaluate the bioengineered arteries before transplantation. Pulmonary artery patches from the most favorable culture conditions were then implanted into juvenile sheep to provide proof of concept. Hematoxylin and eosin staining indicated complete removal of cell nuclei (n = 9), whereas double-stranded DNA isolation from tissue homogenates showed 99.1% DNA removal (p < 0.01, n = 4). Furthermore, trichrome and elastin staining verified maintenance of collagen and elastin. Immunohistochemistry and PCR analyses (n = 4 per group) confirmed contractile smooth muscle presence on only our 3-week pulsatile scaffolds via presence of calponin 1 and myosin heavy chain 11. Tissue bath studies demonstrated that smooth muscle contraction generated by our 3-week pulsatile scaffolds (2.23 ± 0.19 g, n = 4) is comparable with native tissue contraction strength (2.78 ± 0.06 g, n = 4). Ovine transplantation confirmed that our graft can be safely implanted, retains contractile smooth muscle cells, and recruits native endothelium. Longer duration of physiologic pulsatile culture drives differentiation of CPCs seeded on ECM conduits toward a mature, contractile phenotype that is maintained for several weeks in vivo. Longer term studies to assess somatic growth potential are needed. Impact statement The current field of vascular transplantation relies on cadaveric and synthetic grafts to treat right-sided congenital cardiac lesions. These grafts do not grow somatically with our patients. This results in multiple reoperations throughout childhood to increase the size of the graft. Our bioengineered alternative demonstrates successful implantation, contractile smooth muscle cells, and a native endothelial layer. This research demonstrates a pilot study confirming the viability of a bioengineered alternative to the current standard of care in the field of vascular transplantation.

Follow-up of biological reconstruction of epiphysis preserving osteosarcoma around the knee in children: A retrospective cohort study.

Limb salvage treatment for malignant bone tumors in children includes prosthetic and biological reconstruction. Early function following prosthesis reconstruction is satisfactory; however, there are several complications. Biological reconstruction is another way to treat bone defects. We evaluated the effectiveness of reconstruction of bone defects by liquid nitrogen inactivation of autologous bone with preserving epiphysis in 5 cases of periarticular osteosarcoma of the knee. We retrospectively selected 5 patients with articular osteosarcoma of the knee who underwent epiphyseal-preserving biological reconstruction in our department between January 2019 and January 2020. Femur involvement occurred in 2 cases and tibia involvement occurred in 3 cases, with an average defect of 18 cm (12-30 cm). The 2 patients with femur involvement were treated with inactivated autologous bone by liquid nitrogen with vascularized fibula transplantation. Among the patients with tibia involvement, 2 were treated with inactivated autologous bone with ipsilateral vascularized fibula transplantation and 1 was treated with autologous inactivated bone with contralateral vascularized fibula transplantation. Bone healing was evaluated by regular X-ray examination. At the end of the follow-up, lower limb length, knee flexion, and extension function were evaluated. Patients were followed up for 24 to 36 months. Average bone-healing time was 5.2 months (3-8 months). All patients achieved bone healing with no tumor recurrence and no distant metastasis and all patients survived. The lengths of both lower limbs were equal in 2 cases, with shortening by ≤1 cm in 1 case and shortening by 2 cm in 1 case. Knee flexion was >90° in 4 cases and between 50 and 60° in 1 case. The Muscle and Skeletal Tumor Society score was 24.2 (range 20-26). Inactivation of autogenous bone with the epiphysis preserved by liquid nitrogen combined with vascularized fibula reconstruction for periarticular osteosarcoma of the knee in children is safe and effective. This technique supports bone healing. Postoperative limb length and function, and short-term effects were satisfactory.

Decellularized Scaffold-Based Artificial Vascular Patch for Porcine Vascular Repair.

Vascular transplantation is an effective strategy against cardiovascular diseases (CVD), and artificial vascular patches are of urgent need across the world. In this work, we designed a multifunctional decellularized scaffolds (DCS)-based vascular patch for porcine vascular repair. Ammonium phosphate zwitter-ion (APZI) and poly(vinyl alcohol) (PVA) hydrogel were coated on the surface of DCS to improve the mechanical properties and biocompatibility of an artificial vascular patch. Then a heparin (Hep)-loaded metal-organic framework (MOF) further decorated the artificial vascular patches to inhibit blood coagulation and promote vascular endothelialization. The obtained artificial vascular patch showed suitable mechanical properties, good biocompatibility, and blood compatibility. In addition, the proliferation and adhesion of endothelial progenitor cells (EPCs) on the surface of artificial vascular patch improved a lot when compared with unmodified PVA/DCS. According to the results of B-ultrasound and CT images, the artificial vascular patch could maintain the patency of the implant site after implanting into the pig carotid artery. The current results solidly support that a MOF-Hep/APZI-PVA/DCS vascular patch would be an excellent vascular replacement material.

Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor.

Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular graft (SDVG) products available. The design of SDVGs is promising in the future, and SDVG preparation using an in vitro bioreactor is a favorable method, but it faces the problem of long-term culture of >8 weeks. Herein, we used different oxygen (O2) concentrations and mechanical stimulation to induce greater secretion of extracellular matrix (ECM) from cells in vitro to rapidly prepare SDVGs. Culturing with 2% O2 significantly increased the production of the ECM components and growth factors of human dermal fibroblasts (hDFs). To accelerate the formation of ECM, hDFs were seeded on a polycaprolactone (PCL) scaffold and cultured in a flow culture bioreactor with 2% O2 for only 3 weeks. After orthotopic transplantation in rat abdominal aorta, the cultured SDVGs (PCL-decellularized ECM) showed excellent endothelialization and smooth muscle regeneration. The vascular grafts cultured with hypoxia and mechanical stimulation could accelerate the reconstruction speed and obtain an improved therapeutic effect and thereby provide a new research direction for improving the production and supply of SDVGs.

Developing small-diameter vascular grafts with human amniotic membrane: long-term evaluation of transplantation outcomes in a small animal model

While current clinical utilization of large vascular grafts for vascular transplantation is encouraging, tissue engineering of small grafts still faces numerous challenges. This study aims to investigate the feasibility of constructing a small vascular graft from decellularized amniotic membranes (DAMs). DAMs were rolled around a catheter and each of the resulting grafts was crosslinked with (a) 0.1% glutaraldehyde; (b) 1-ethyl-3-(3-dimethylaminopropyl) crbodiimidehydro-chloride (20 mM)-N-hydroxy-succinimide (10 mM); (c) 0.5% genipin; and (d) no-crosslinking, respectively. Our results demonstrated the feasibility of using a rolling technique followed by lyophilization to transform DAM into a vessel-like structure. The genipin-crosslinked DAM graft showed an improved integrated structure, prolonged stability, proper mechanical property, and superior biocompatibility. After transplantation in rat abdominal aorta, the genipin-crosslinked DAM graft remained patent up to 16 months, with both endothelial and smooth muscle cell regeneration, which suggests that the genipin-crosslinked DAM graft has great potential to be implemented as a small tissue engineered graft for future vascular transplantation.

Poly(ferulic acid)-hybrid nanofibers for reducing thrombosis and restraining intimal hyperplasia in vascular tissue engineering

Small-diameter blood vascular transplantation failure is mainly caused by the vascular materials' unreliable hemocompatibility and histocompatibility and the unmatched mechanical properties, which will cause unstable blood flow. How to solve the problems of coagulation and intimal hyperplasia caused by the above factors is formidable in vascular replacement. In this work, we have synthesized poly(ferulic acid) (PFA) and prepared poly(ester-urethane)urea (PEUU)/silk fibroin (SF)/poly(ferulic acid) (PFA) hybrid nanofibers vascular graft (PSPG) by random electrospinning and post-double network bond crosslinking for process optimization. The results in vitro demonstrated that the graft is of significant anti-oxidation, matched mechanical properties, reliable cytocompatibility, and blood compatibility. Replacing resected rat abdominal aorta and rabbit carotid artery models with PSPG vascular grafts indicated that the grafts are capable of homogeneous hybrid PFA significantly promoted the stabilization of endothelial cells and the ingrowth of smooth muscle cells, meanwhile stabilizing the immune microenvironment. This research demonstrates the PSPG vascular graft with substantial patency, indicating their potential for injured vascular healing.

Vascular reconstructions and transplant technologies in liver surgery (part I)

To systematize technical aspects of liver resections with reconstruction of afferent and efferent liver blood supply and/or inferior vena cava, as well as to analyze the results of surgical treatment in patients with focal liver lesions. The study included 413 patients with parasitic lesions, primary and secondary liver tumors with great vessel invasion (portal vein, hepatic artery, hepatic veins, inferior vena cava, right atrium). These features excluded radical liver resections without vascular resection and reconstruction, as well as liver autotransplantation in vivo, liver autotransplantation ante situ (ex situ in vivo), extracorporeal liver resections with autotransplantation (ex vivo). Surgical interventions were systematized depending of surgical tactics and techniques, technical complexity, type and number of reconstructed vessels, the use of total vascular isolation and cold preservation techniques, resection and reconstruction of great vessels. Thus, 4 gradations were allocated (Grade I-IV). The definition of transplantation technologies in liver surgery was proposed. Transplantation technologies in liver surgery include liver resections supplemented with vascular reconstruction of afferent and efferent liver blood supply, inferior vena cava including total vascular isolation of liver under normo- or hypothermia. These measures can significantly extend the possibilities of resection.

The Effect of Lymphangiogenesis in Transplant Arteriosclerosis.

Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown. Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1-CreERT2;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2KO, Foxn1KO, and lghm/lghdKO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis. Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts. Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

The Value of Upper Extremity, face, and uterus transplantation: A Summit Conference

A panel of over 60 experts in the field of vascular composite allotransplantation from around the United States gathered on November 8, 2019 at the Uniformed Services University of the Health Sciences, in Bethesda MD. Experts in the field were recruited and invited through a collaborative effort of the American Society for Reconstructive Transplantation, the American Society of Transplantation, the American Society for Reproductive Medicine, and the American Society of Transplant Surgeons in order to discuss The Value of Upper Extremity, Face, and Uterus Transplantation: A Summit Conference . All sessions were directed by a moderator and focused on indications and contraindications, outcomes and costs of vascular composite allotransplantations in order to evaluate and discuss the state of the art science in the field. Representatives of major vascular composite allotransplantation centers in North America (Cleveland Clinic, University of Pennsylvania, Brigham and Women’s Health, New York University, the Mayo Clinic, Baylor, John Hopkins University, the University of Louisville) collaborated in order to present the combined experience of the major transplant centers in the United States. The panel members developed consensus guidelines for publication demonstrating success and unity amongst the vascular composite allotransplantation and solid organ transplantation communities. • A panel of 60 vascular composite allotransplantation experts from around the United States met in Bethesda, MD on November 8, 2019. • Indications, contraindication, outcomes and complications of face, hand and uterus transplantation were discussed. • This consensus meeting served to propel the field of vascular allograft transplantation through unity.

The proteins derived from platelet-rich plasma improve the endothelialization and vascularization of small diameter vascular grafts

Vascular transplantation has become an ideal substitute for heart and peripheral vascular bypass therapy and tissue-engineered vascular grafts (TEVGs) present an attractive potential solution for vascular surgery. However, small diameter (Ф < 6 mm) vascular do not have ideal TEVGs for clinical use. Platelet-rich plasma (PRP), a key source of bioactive molecules, has been confirmed to promote tissue repair and regeneration. In this study, we prepared PRP-loaded TEVGs (PRP-TEVGs) by electrospinning, investigated the characterization of TEVGs, and verified the effect of PRP-TEVGs in vivo and in vitro experiments. The results suggested that PRP-TEVGs had good biocompatibility, released growth factors stably, promoted cell proliferation and migration significantly, up-regulated the expression of endothelial NO synthase (eNOS) in functional vascular endothelial cells (VECs), and maintained the stability of the endothelial structure. In vivo experiments suggest that PRP can promote rapid endothelialization and reconstruction of TEVGs. Overall, this finding indicated that PRP could promote the rapid vascular endothelialization of small-diameter TEVGs by improving contractile vascular smooth muscle cells (VSMCs) regeneration, and maintaining the integrity and functionality of VECs.

Construction of functional magnetic scaffold with temperature control switch for long-distance vascular injury

Fusion of endothelial monolayer for rapid reendothelialization is the key to vascular transplantation, which is crucial for remodeling long-distance (≥10 mm) vascular injury (LDVJ) and reducing the long-term repair period. Although silk fibroin (SF) has been widely prepared as a scaffold to repair vascular injuries, it is still challenging to remodel LDVJs. The design and manufacture of functional scaffolds with a rapid reendothelialization enhancement effect are helpful to solve this problem. Here, we developed a well-designed functional magnetic scaffold (MDP) with a temperature-controlled switch, intelligently regulating the release of magnetic nanoparticles (MNPs) to induce macrophages migration and M2 polarization. The results show that the radial support force of MDP is appropriately five times higher than that of pure silk fibroin scaffold (SFC), and the degradation of MDP is delayed, which is beneficial to maintaining the integrity of the scaffold. MDP induces the migration of macrophages, upregulates the expression of repair cytokines such as TGF-β, IL-10 and VEGF, and promotes the proliferation of mouse aortic vascular smooth muscle (MOVAS) cells. More importantly, the enhanced migration of macrophages at the phase transition temperature is more conducive to the proliferation and accumulation of vascular repair-related cells, which is conducive to rapid reendothelialization. In addition, MDP also significantly regulates the polarization of macrophages to M2 type, which is conducive to the secretion of repair cytokines to further promote vascular recovery. The evaluation of endothelial cells' adhesion and function also proved that MDP could increase the expression of vascular endothelial cadherin (VE-Cad) and collagen IV (COL IV) and has the potential for rapid reendothelialization. The replacement model in vivo animal experiments further proved that MDP exhibited a better repair effect than SFC, providing a new option for the repair of LDVJ in the future.