Bioengineered Acellular Vessel Implantation in a Patient with Chronic Limb-Threatening Ischemia: A Case Report and Discussion of Implications for Trauma

The ideal conduit for vascular reconstruction is one that can be obtained “off the shelf” and demonstrates long-term patency, tissue incorporation and resistance to infection. Currently available conduits, such as autologous vein and synthetic grafts, are limited in one or more of these areas. The Human Acellular Vessel (HAV), a bioengineered, acellular blood vessel, can be obtained “off the shelf” and has shown promise in each of these properties. We describe a case in which the HAV was utilized for open bypass reconstruction in a patient with chronic limb-threatening ischemia who lacked alternative reconstructive options. The case is followed by a discussion of potential broader applications of this novel implant, specifically in the management of vascular trauma.

Electrospun fibre diameter and its effects on vascular smooth muscle cells

Bypass grafting is a technique used in the treatment of vascular disease, which is currently the leading cause of mortality worldwide. While technology has moved forward over the years, synthetic grafts still show significantly lower rates of patency in small diameter bypass operations compared to the gold standard (autologous vessel grafts). Scaffold morphology plays an important role in vascular smooth muscle cell (VSMC) performance, with studies showing how fibre alignment and surface roughness can modulate phenotypic and genotypic changes. Herein, this study has looked at how the fibre diameter of electrospun polymer scaffolds can affect the performance of seeded VSMCs. Four different scaffolds were electrospun with increasing fibre sizes ranging from 0.75 to 6 µm. Culturing VSMCs on the smallest fibre diameter (0.75 µm) lead to a significant increase in cell viability after 12 days of culture. Furthermore, interesting trends were noted in the expression of two key phenotypic genes associated with mature smooth muscle cell contractility (myocardin and smooth muscle alpha-actin 1), whereby reducing the fibre diameter lead to relative upregulations compared to the larger fibre diameters. These results showed that the smallest (0.75 µm) fibre diameter may be best suited for the culture of VSMCs with the aim of increasing cell proliferation and aiding cell maturity.

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane

Coronary artery disease is one of the major diseases that plagues today’s modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5–8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young’s modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering

Materials used for knee ligament grafting

The authors have presented the review of scientific literature on producing grafts intended for surgical reconstruction of ligament ruptures. The treatment of ligament ruptures in reconstructive plastic surgery could be performed by using synthetic grafts, autologous and allogenic grafts from tissue donors. Advantages of synthetic grafts include the possibility of their regular manufacturing under sterile conditions, and providing mechanical properties, high biocompatibility. However, synthetic implants significantly increase the risk of synovitis and other complications, they can not be replaced by the native tissue, and have no ability to regeneration. Autologous grafts have ideal tissue compatibility and quick biointegration, could be harvested from different anatomical sites, but commonly the graft harvesting is followed by donor site morbidity and potential risk of injury nerves, elongates operation time, bad cosmetic results. The use of autografts may be also limited by anatomical features of the patient. Allogenic ligament biomaterial could provide wide range of grafts, but in our days there is no standardized methods for ligament graft sterilization and long storage. Wellknown sterilization methods, such as ionized radiation and chemical treatment, gave controversial results. One could conclude that estimation of ligament graft viability must include a complex study of biomechanical properties, cell and fibers integrity.

Inflammasomes in the Pathophysiology of Aortic Disease

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

Bioengineering silk into blood vessels

The rising incidence of cardiovascular disease has increased the demand for small diameter (<6 mm) synthetic vascular grafts for use in bypass surgery. Clinically available synthetic grafts (polyethylene terephthalate and expanded polytetrafluorethylene) are incredibly strong, but also highly hydrophobic and inelastic, leading to high rates of failure when used for small diameter bypass. The poor clinical outcomes of commercial synthetic grafts in this setting have driven significant research in search of new materials that retain favourable mechanical properties but offer improved biocompatibility. Over the last several decades, silk fibroin derived from Bombyx mori silkworms has emerged as a promising biomaterial for use in vascular applications. Progress has been driven by advances in silk manufacturing practices which have allowed unprecedented control over silk strength, architecture, and the ensuing biological response. Silk can now be manufactured to mimic the mechanical properties of native arteries, rapidly recover the native endothelial cell layer lining vessels, and direct positive vascular remodelling through the regulation of local inflammatory responses. This review summarises the advances in silk purification, processing and functionalisation which have allowed the production of robust vascular grafts with promise for future clinical application.

Patellar tendon versus artificial grafts in anterior cruciate ligament reconstruction: a systematic review and meta-analysis

Background The aim of anterior cruciate ligament reconstruction (ACLR) is to restore the function of the knee joint, protect the cartilage, and reduce the occurrence of osteoarthritis. However, due to the structural limitations of the human body, it is not possible to perform ACLR with conventional sutures. To restore normal functioning of the anterior cruciate ligament (ACL), a new ligament must be reconstructed in the position of the previous ACL. Objective To compare autografts and synthetic grafts in terms of postoperative knee stability and function Search methods The protocol for this study was registered with PROSPERO (CRD42021243451). Two reviewers independently searched the PubMed, Embase, and the Cochrane Library databases from database inception though February 10, 2021. The following search method was used: ((Autograft) OR (Autologous) OR (Autotransplant)) OR Artificial Ligament AND (Anterior Cruciate Ligament Injury [MeSH Terms]) AND (Randomized controlled trial [MeSH Terms]). Methodological quality was assessed by the Cochrane risk of bias tool. Selection criteria We only included randomized controlled trials (level I) that compared autograft and synthetic graft interventions in participants with ACL injury. We included trials that evaluated ACLR using at least one outcome (Lachman test, pivot shift test, IKDC grades, or complications). Results A total of 748 studies were identified in the initial literature search, and seven studies that examined only bone-patellar tendon-bone (BPTB) grafts compared with artificial grafts met the predetermined inclusion criteria. The results showed that BPTB grafts were associated with significantly better pivot shift test and Lachman test results and better IKDC grades and lower complication rates than synthetic grafts. Conclusions This review indicates that for adults, BPTB grafts perform more favorably than synthetic grafts in ACLR in terms of knee stability, function, and complication. More research is needed to compare autologous tendons and allogeneic tendons with artificial ligaments, especially in elderly individuals. Level of evidence Level I, systematic review and meta-analysis

Massive Chondrolysis and Joint Destruction after Artificial Anterior Cruciate Ligament Repair

The Ligament Augmentation Reconstruction System (LARS) is an artificial ligament made of polyethylene terephthalate (PET) used for anterior cruciate ligament (ACL) reconstruction in Australia. Poor results with previous generations of synthetic grafts causing synovitis, graft failure, and premature osteoarthritis have encouraged the production of the newer LARS ligament with good results. We present a case of massive chondrolysis and joint destruction after LARS implantation requiring total knee replacement in a 23-year-old male. This case documents a rare and severe complication to the LARS ligament as caution for the implementation of this device in young athlete.