Creation Of Grafts Research Articles

Understanding the Structure-Function Relationship through 3D Imaging and Biomechanical Analysis: A Novel Methodological Approach Applied to Anterior Cruciate Ligaments.

Understanding the microstructure of fibrous tissues, like ligaments, is crucial due to their nonlinear stress-strain behavior from unique fiber arrangements. This study introduces a new method to analyze the relationship between the microstructure and function of anterior cruciate ligaments (ACL). We tested the procedure on two ACL samples, one from a healthy individual and one from an osteoarthritis patient, using a custom tensioning device within a micro-CT scanner. The samples were stretched and scanned at various strain levels (namely 0%, 1%, 2%, 3%, 4%, 6%, 8%) to observe the effects of mechanical stress on the microstructure. The micro-CT images were processed to identify and map fibers, assessing their orientations and volume fractions. A probabilistic mathematical model was then proposed to relate the geometric and structural characteristics of the ACL to its mechanical properties, considering fiber orientation and thickness. Our feasibility test indicated differences in mechanical behavior, fiber orientation, and volume distribution between ligaments of different origins. These indicative results align with existing literature, validating the proposed methodology. However, further research is needed to confirm these preliminary observations. Overall, our comprehensive methodology shows promise for improving ACL diagnosis and treatment and for guiding the creation of tissue-engineered grafts that mimic the natural properties and microstructure of healthy tissue, thereby enhancing integration and performance in biomedical applications.

Platelet-rich fibrin in rhinoplasty: A precise and standardized approach

Rhinoplasty is a complex procedure. To achieve the expected aesthetic result, surgeons often use grafts both for structural and camouflage purposes. The perfect camouflage graft should be soft, malleable and precisely tailored to the patient's needs, with as few donor sites as possible. The use of diced cartilage has been widely described, but it cannot be used as a free graft in all cases. Platelet-rich fibrin is an interesting matrix for the creation of soft grafts with great precision and high reproducibility while promoting biocellular regeneration via growth factors. This article describes the use of platelet-rich fibrin in liquid and solid forms for the creation of standardized soft grafts with diced cartilage. We detail the procedure, and present the different grafts created by the author for dorsal camouflage and augmentation, tip management, and revision rhinoplasty.

Design and testing of a humanized porcine donor for xenotransplantation

Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts.

Роль клеток стромы в ангиогенезе кожных ран: обзор литературы

INTRODUCTION: The study of skin wound regeneration has not lost its relevance, especially among surgeons. Angiogenesis is a key factor in wound healing. It is known that the optimal blood supply provides the tissue with nutrients, growth factors, immune cells necessary for the complete repair of skin defect. Insufficient ability to restore functional blood supply to the wound area can lead to chronic non-healing wounds. Therefore, the identification and validation of various factors influencing angiogenesis in the wound bed is of great interest for the development of potential therapeutic agents. The aim of this review is to highlight the current understanding of the mechanisms and morphological manifestations of skin wound angiogenesis, as well as the functional significance of stromal cells involved in this process. The contribution of macrophages, pericytes, mast cells, telocytes to the mechanisms of formation of microcirculatory vessels is shown. The search for literary sources was carried out in the electronic systems eLIBRARY.RU and PubMed by the main keywords of the topic: histology, skin wound regeneration, angiogenesis, stromal cells, macrophages, mast cells, pericytes, telocytes. The publications were analyzed over the last 12 years. The criteria for including a research in the review were the simultaneous mention of several keywords in the article. CONCLUSION: Analysis of the literature demonstrates the relevance of the study of angiogenesis. Modern morphological methods permitted to describe complex intercellular interactions providing the growth of the vascular network. Despite the large number of studies in this area, morphological data are constantly being supplemented to expand the potentials of histological and immunohistochemical studies. Cellular interactions during wound healing are being actively studied and confirmed to be used in the study of the mechanisms of action of drugs and in the development of new methods for treating wounds of various origin. This is of great importance, for example, in search for new reconstructive technologies, for creation of blood vessel grafts, and for development of endothelial prostheses based on non-degradable synthetic materials.

Template for Diced Cartilage with Platelet-Rich Fibrin (PRF) in Rhinoplasty: An Easy Solution for Millimetric Camouflage of the Full Dorsal Esthetic Unit.

Dorsal irregularities are one of the most common issues in modern rhinoplasty. Rhinoplasty surgeons propose placing interface grafts lining the hole dorsum to ensure a natural unoperated look. Diced cartilage embedded in Choukroun's platelet-rich fibrin (PRF) scaffold being one of the most recent innovations in the field. However, no method has been described to help with the creation of thin, malleable, and reproductive graft with millimetric precision using that technique. The senior author details his protocol and his experience with a newly developed template for the creation of reproductive grafts with standard size and thickness, using diced cartilage, injectable PRF (iPRF), and advanced PRF (aPRF), for full dorsal camouflage and lining in rhinoplasty. This retrospective case series was conducted to evaluate the results looking at the dorsal esthetic unit at a minimum of 6 months for patients who beneficiated from a millimetric dorsal augmentation from 1 to 2mm using diced cartilage with iPRF and aPRF. The author reports his experience with 54 cases operated from April 2018 to May 2022 using his newly developed template.The template is an innovative technique to allow faster and more reliable fabrication of soft grafts using diced cartilage with both iPRF and aPRF. This novel approach allows for millimetric dorsal augmentation from 1 to 2mm with great precision and high reproductivity with good esthetic outcome.

Surgical creation of upper extremity arteriovenous fistula and grafts: a narrative review.

Surgical creation of arteriovenous fistulas (AVF) and grafts (AVG) continues to be the mainstay access for hemodialysis (HD). Avoidance of dependence on dialysis catheters continues to be a worldwide mission in dialysis access. Importantly, there is no one-size-fits-all approach to hemodialysis access and each patient should undergo access creation that is patient-centered. The aim of this paper is to review the literature, current guidelines, and discuss the common types of upper extremity hemodialysis access and their reported outcomes. We will also share our institutional experience regarding the surgical creation of upper extremity hemodialysis access. The literature review incorporates twenty-seven relevant articles from 1997 to present and one case report series from 1966. Sources were gathered from electronic databases including PubMed, EMBASE, Medline, and Google Scholar. Only articles written in the English language were considered and study designs varied from current clinical guidelines, systematic and meta-analyses, randomized controlled trials, observational studies, and two main vascular surgery textbooks. This review exclusively focuses on the surgical creation of upper extremity hemodialysis accesses. Creating a graft versus fistula ultimately is decided by the existing anatomy, and is centered around the need of the patient. Preoperatively, the patient should undergo a thorough history and physical exam, with special attention to any previous central venous access, as well as, delineating the vascular anatomy with ultrasound imaging. The major tenets of access creation are choosing the most distal site of the non-dominant upper extremity whenever possible; and ideally creation of an autogenous access is preferred over a prosthetic graft. Described in this review are multiple surgical approaches for upper extremity hemodialysis access creation and associated institutional practices performed by the surgeon author. In the postoperative period, follow up care and surveillance are imperative to preserve a functioning access. The most recent guidelines regarding hemodialysis access still favor arteriovenous fistula as the primary goal for patients with suitable anatomy. Preoperative evaluation including patient education, intraoperative ultrasound assessment, meticulous technique, and careful postoperative management are all paramount for successful access surgery. Dialysis access remains quite challenging, but with diligence the great majority of patients can be dialyzed without catheter dependence.

Surgical creation of lower extremity fistula and grafts.

Lower limb vascular access (LLVA) should be considered for patients in whom upper extremity access has been exhausted. The decisional process around vascular access (VA) site selection should incorporate a patient centered approach that aligns with End Stage Kidney Disease life-plan as recently described in proffered in 2019 Vascular Access Guidelines. The current surgical approaches to LLVA can be divided into two main groups: (A) autologous arteriovenous fistulas (AVFs); (B) synthetic arteriovenous grafts (AVGs). The autologous AVFs include both the femoral vein (FV) and great saphenous vein (GSV) transpositions, while prosthetic AVGs in the thigh position are appropriate for certain patient subtypes. Good durability has been described for autogenous FV transposition as well as AVGs with both demonstrating acceptable primary and secondary patency rates. Major complications such as steal syndrome, limb edema, and bleeding and minor complications such as wound-related infection, hematoma and delayed wound healing have been noted. LLVA is commonly reserved for the patient in whom the only alternative VA may be a tunneled catheter with its attendant morbidity. In this clinical circumstance, successful LLVA has the opportunity to be a life-saving surgical therapy when successfully performed. We describe a thoughtful approach that focuses on patient selection to optimize success and mitigate complications associated with LLVA.

Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ.

Transfer of regenerative approaches into clinical practice is limited by strict legal regulation of in vitro expanded cells and risks associated with substantial manipulations. Isolation of cells for the enrichment of bone grafts directly in the Operating Room appears to be a promising solution for the translation of biomedical technologies into clinical practice. These intraoperative approaches could be generally characterized as a joint concept of tissue engineering in situ. Our review covers techniques of intraoperative cell isolation and seeding for the creation of tissue-engineered grafts in situ, that is, directly in the Operating Room. Up-to-date, the clinical use of tissue-engineered grafts created in vitro remains a highly inaccessible option. Fortunately, intraoperative tissue engineering in situ is already available for patients who need advanced treatment modalities.

3D Bioprinting of Prevascularized Full-Thickness Gelatin-Alginate Structures with Embedded Co-Cultures.

The use of bioprinting allows the creation of complex three-dimensional cell laden grafts with spatial placements of different cell lines. However, a major challenge is insufficient nutrient transfer, especially with the increased size of the graft causing necrosis and reduced proliferation. A possibility to improve nutrient support is the integration of tubular structures for reducing diffusion paths. In this study the influence of prevascularization in full-thickness grafts on cell growth with a variation of cultivation style and cellular composition was investigated. To perform this, the rheological properties of the used gelatin-alginate hydrogel as well as possibilities to improve growth conditions in the hydrogel were assessed. Prevascularized grafts were manufactured using a pneumatic extrusion-based bioprinter with a coaxial extrusion tool. The prevascularized grafts were statically and dynamically cultured with a monoculture of HepG2 cells. Additionally, a co-culture of HepG2 cells, fibroblasts and HUVEC-TERT2 was created while HUVEC-TERT2s were concentrically placed around the hollow channels. A static culture of prevascularized grafts showed short-term improvements in cell proliferation compared to avascular grafts, while a perfusion-based culture showed improvements in mid-term cultivation times. The cultivation of the co-culture indicated the formation of vascular structures from the hollow channels toward avascular areas. According to these results, the integration of prevascular structures show beneficial effects for the in vitro cultivation of bioprinted grafts for which its impact can be increased in larger grafts.

Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique

There is great interest in the development of techniques to bioengineer pulsatile myocardial tissue as a next-generation regenerative therapy for severe heart failure. However, creation of thick myocardial grafts for regenerative medicine requires the incorporation of blood vessels. In this study, we describe a new method of constructing a vascular network in vivo that allows the construction of thick human myocardial tissue from multi-layered cell sheets. A gelatin sheet pre-loaded with growth factors was transplanted onto the superficial femoral artery and vein of the rat. These structures were encapsulated together within an ethylene vinyl alcohol membrane and incubated in vivo for 3 weeks (with distal superficial femoral artery ligation after 2 weeks to promote blood flow to the vascular bed). Subsequently, six cardiomyocyte sheets were transplanted onto the vascular bed in two stages (three sheets, two times). Incubation of this construct for a further week generated vascularized human myocardial tissue with an independent circulation supplied by an artery and vein suitable for anastomosis to host vessels. Notably, laminating six cell sheets on the vascular bed in two stages rather than one allowed the creation of thicker myocardial tissue while suppressing tissue remodeling and fibrosis. Finally, the pulsatile myocardial tissue was shown to generate auxiliary pressure when wrapped around the common iliac artery of a rat. Further development of this technique might facilitate the generation of circulatory assist devices for patients with heart failure.

1-year outcomes results of coronary artery bypass grafting in patients with target artery distal calcinosis

Aim. Comparative assessment of the surgical strategies and one-year results of coronary artery bypass grafting (CABG) in patients with and without target artery distal calcinosis.Methods. A prospective study from January 2017 to October 2018 included 462 patients with coronary artery disease. All patients underwent CABG. Groups were formed according to coronary angiography data. Group 1 — patients with target artery distal calcinosis (n = 108). Group 2 — patients without any marks of coronary calcification (n = 354). To minimize systematic errors and maximize their comparability, computer correction was performed using propensity score matching (group 1, n = 106, group 2, n = 106). Intraoperative data and one-year outcomes were analyzed and compared.Results. Following the strategy for complete revascularization, we had to form a greater number of distal anastomosis in group 1 due to severe coronary atherosclerosis. The index of revascularization was higher in group 1 (4.4 ± 0.7 and 3.9 ± 0.8, p = 0.001). We registered a higher frequency of using prolonged patch-angioplasty (21.7 versus 1.8 %, p < 0.001), anastomosis with artery diameter < 1.5 mm (33.9 versus 16 %, p < 0.003), coronary artery endarterectomy (13.2 versus 0.9%, p < 0.001) in patients with coronary artery calcinosis. As well as the creation of composite grafts, such as Y-graft (33 versus 8.5 %, p < 0.001) and sequential graft (13.9 versus 5.7 %, p = 0.03) were higher in group 1. The use of adjunctive surgical techniques in the main group significantly increased the duration of cardio-pulmonary bypass and aortic cross-clamp time. The primary endpoints – coronary ischemic events – angina recurrence (10.3 versus 6.3 %, p = 0.307), myocardial infarction (3.1 versus 2.1 %, p = 0.654), the need for re-revascularization (3.1 versus 1 %, p = 0.318) were comparable in 1 year after surgery. Overall mortality was relatively low in both groups.Conclusion. CABG in patients with target artery distal calcinosis is associated with similar one-year outcomes compared to CABG in patients without coronary artery calcification. The positive results of CABG in patients with target artery distal calcinosis indicate the benefits of complete myocardial revascularization, despite the long duration and complexity of interventions. Received 29 September 2021. Revised 20 October 2021. Accepted 22 October 2021. Funding: The work was carried out within the framework of the state assignment (No. AAAA-A18-118022290040-7). Conflict of interest: Authors declare no conflict of interest. Contribution of the authors:Conception and study design: A.A. Shiryaev, G.B. Mayorov, D.M. GalayutdinovData collection and analysis: G.B. Mayorov, S.K. Kurbanov, V.Yu. ZaikovkiiStatistical analysis: S.K. Kurbanov, G.B. MayorovDrafting the article: G.B. Mayorov, A.V. Andreev, S.K. KurbanovCritical revision of the article: R.S. Akchurin, A.A. Shiryaev, D.M. Galayutdinov, V.P. VasilievFinal approval of the version to be published: R.S. Akchurin, A.A. Shiryaev, D.M. Galayutdinov, V.P. Vasiliev, S.K. Kurbanov, A.V. Andreev, V.Yu. Zaikovkii, G.B. Mayorov

Aspects of Lyophilization of Cardiac Bioimplant

The use of implants of biological origin in clinical practice has led to the search for methods of long-term storage of tissues without damaging their functional and structural characteristics. Xenografts (extracted from pericardium of pigs, horses, bulls) are drawing more and more interest. The bovine pericardium is exposed to chemical and physical factors providing complete purification of tissue from cells and their components. Such scaffolds are protein (collagen) complexes that fully replicate the microstructure of the pericardial tissue. Lyophilisation ensures long-term preservation of the extracellular matrix properties. The principle of the method is in drying pre-frozen tissue, in which water is sublimated. The method is intended for storage, transportation, and the subsequent use of the bioimplant in clinical practice. However, the lyophilization process may be accompanied by various undesirable factors that can lead to denaturation of the matrix protein or loss of its functionality and structure. To preserve the natural microstructure, stabilizers or various modifications (slow/fast freezing, reducing the degree of supercooling, etc.) of the lyophilization process are applied to biological prostheses. In this review, the main processes of lyophilization of biological tissue are described, which can affect the operation of a cardiac implant. A deep understanding of the parameters of the lyophilization process is crucial for creation of stable tissue grafts and their subsequent long-term storage.

Evaluation of the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer composition with atrombogenic and antimicrobial drug coating

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p < 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p < 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p < 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications.

Quo vadimus? Fundamental problems of developing hybrid prostheses of thoracic aorta

This article is a review briefly characterizing the state of the art of hybrid surgery of the thoracic aorta using the frozen elephant trunk technique worldwide and in Russia, also discussing unsolved problems of fundamental science, being key issues in creation of new models of hybrid prostheses of the thoracic aorta. The main attention is paid to the problem of radial stiffness of the stent-graft portion of the prosthesis. Performed is a detailed analysis of the factors influencing this characteristic of the sent graft: shape, size and number of cells of the stent element, thickness of the nitinol wire it is made of, method of edge connection, nitinol properties depending on the alloy grade and methods of thermoforming. It is shown that excessive stiffness leads to the development of d-SINE syndrome. This is followed by discussing the problem of optimal stiffness of stent grafts, based on the design of stent graft elements and elastic properties of the wall of the true channel of a dissecting aortic aneurysm. Also proposed is an approach to solving the problem of d-SINE, consisting in creation of conical stent grafts and/or a gradual decrease of radial stiffness of stent elements in the direction of the distal portion. Comprehensively addressed are disadvantages of the graft portion of the prosthesis, in 95% of items made of polyethylene terephthalate fiber: susceptibility to degradation associated with manufacturing defects and intraoperative microdamages, abrasive effect in the zone of contact with stent elements, partial postoperative hydrolysis and an inflammatory reaction to a foreign body, often being clinically pronounced. Also touched upon are certain aspects of creating hermetic coatings of the graft portion, with the use of vancomycin possessing low cytotoxicity as part of an antibacterial component being promising. As a whole, it is demonstrated that advances in creating a novel generation of hybrid prostheses should be associated with new approaches and materials, to be obtained at the junction of medicine and fundamental sciences.

A Randomized Trial of Liposomal Prednisolone (LIPMAT) to Enhance Radiocephalic Fistula Maturation: A Pilot Study

Patients on maintenance hemodialysis (HD) require a reliable vascular access; however, only half of newly created radiocephalic arteriovenous fistulas (RCAVF) can be used for HD without additional procedures to promote maturation and up 25% fail to provide adequate vascular access for HD.1 The need for subsequent creation of upper arm arteriovenous fistulas (AVFs) and arteriovenous grafts may decrease if maturation can be improved. Currently, no pharmacological treatments have been proven to improve clinical maturation of AVFs.

Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds.

Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bioengineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we developed laryngeal scaffolds which were generated by detergent perfusion-decellularization over 9 days and preserved their glycosaminoglycan content and biomechanical properties of a native larynx. After subcutaneous implantations in rats for 14 days, the scaffolds did not elicit a CD3 lymphocyte response. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated reendothelialized arterial and venous vascular beds. Under the same culture medium, we bioengineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in an intramuscular transplantation model in immunodeficient mice. We supported formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing complex, multicellular, ready-to-transplant tissue grafts. Impact Statement For patients undergoing laryngectomy, no reconstruction methods are available to restore the complex functions of the human larynx. The first promising preclinical results have been achieved with the use of biological scaffolds fabricated from decellularized tissue. However, the complexity of laryngeal tissue composition remains a hurdle to create functional viable grafts, since previously each cell type requires tailored culture conditions. In this study, we report the de novo formation of three humanized laryngeal tissue compartments under one uniform culture condition, a possible keystone in creating vital composite tissue grafts for laryngeal regeneration.

Tumor Cell Behavior in Porous Hydrogels: Effect of Application Technique and Doxorubicin Treatment.

The effect of porosity on diffusion characteristics of scaffolds and invasive capacity of MCF-7 and PC-3 tumor cells was studied for gelatin hydrogels. According to MTS test results, the efficiency of population of a macroporous cryogel by cells applied by different techniques increased in the following order: migration from the monolayer<surface adhesion<<injection. Tumor cells in the cryogel differed by the migration and aggregation activity; injection route ensured a more uniform and dense population. In the cryogel-based culture, the cytotoxic effect of doxorubicin was 3-lower than in monolayer culture, which can be explained by supporting effect of the scaffold on cell growth and clustering. The results are of interest for the creation of tumor models and grafts with controlled properties.

Creation of Arteriovenous Fistulas and Grafts Concomitantly with Endovascular Correction of Outflow Veins: A Hybrid Procedure

Achieving well-functioning dialysis fistulas is a common problem in dialyzed patients, and it is mainly caused by the pathologies of vessels used for fistula creation. Hybrid therapies, combining surgical and endovascular procedures, potentially enable the creation of functional dialysis fistulas in patients with vessels that are otherwise unsuitable for vascular access. Between January 1, 2014 and June 30, 2018, we created dialysis fistulas simultaneously with endovascular correction of outflow pathologies in 15 patients. The included patients had a long history of dialysis (median 10.5years, range 3-22) and many previous dialysis access procedures (mean 5.3 procedures, range 2-9). In 13 patients (86.7%), the fistula was created on the upper arm; in 5 patients (33.3%), it was arteriovenous graft done with polytetrafluoroethylene (PTFE) prosthesis (in an additional 3 patients, a PTFE prosthesis was used to extend the vein), and 7 patients had native vessel fistulas (46.7%). Endovascular procedures, in some cases performed on more than 1 vein, were applied for correction of the subclavian vein (8 patients, 53.3%); brachiocephalic vein (6 patients, 40.0%); cephalic, basilic, and axillary veins (2 patients each, 13.3%); and superior cava vein (1 patient, 6.7%). Access for the endovascular procedure was achieved through a dissected vein used for arteriovenous anastomosis. The fistula function was monitored, and all complications of dialysis access were noted. The median follow-up in the observed group was 18months. We compared the patency of dialysis fistula creation combined with endovascular correction of outflow vein pathology to our results of standard dialysis fistula operations: radiocephalic dialysis fistula creation (RCAVF group, 65 patients) and dialysis fistula stenosis angioplasty (PTA group, 30 patients). The 12- and 24-month primary patency rates of dialysis fistulas created in hybrid procedures with simultaneous outflow vein pathology correction were 72.7% and 63.6%, respectively. No early complications related to endovascular or open procedures were observed. A hybrid procedure for the creation of a dialysis fistula with the simultaneous correction of outflow pathologies enables a properly functioning dialysis fistula to be obtained. This procedure can be performed in patients with complicated vascular situations, enabling the creation of dialysis fistulas. Our results of hybrid procedures, involving simultaneous endovascular correction of the outflow vein with dialysis fistula creation, showed the efficiency and good results.

Investigational growth factors utilized in animal models of spinal fusion: Systematic review.

BACKGROUNDOver 400000 Americans annually undergo spinal fusion surgeries, yet up to 40% of these procedures result in pseudoarthrosis even with iliac crest autograft, the current “gold standard” treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors (e.g., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal fusion.AIMTo review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for translation.METHODSWe conducted a systematic review of the literature using PubMed, Embase, Cochrane Library, and Web of Science databases with searches run on May 29th, 2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion, animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates, and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic review.RESULTSTwenty-six articles were included in this study, comprising 14 experimental growth factors: AB204 (n = 1); angiopoietin 1 (n = 1); calcitonin (n = 3); erythropoietin (n = 1); basic fibroblast growth factor (n = 1); growth differentiation factor 5 (n = 4), combined insulin-like growth factor 1 + transforming growth factor beta (n = 4); insulin (n = 1); NELL-1 (n = 5); noggin (n = 1); P-15 (n = 1); peptide B2A (n = 2); and secreted phosphoprotein 24 (n = 1). The fusion rates of the current gold standard treatment (autologous iliac crest bone graft, ICBG) and the leading clinically used growth factor (BMP-2) ranged widely in the included studies, from 0-100% for ICBG and from 13%-100% for BMP-2. Among the identified growth factors, calcitonin, GDF-5, NELL-1, and P-15 resulted in fusion rates of 100% in some cases. In addition, six growth factors - AB204, angiopoietin 1, GDF-5, insulin, NELL-1, and peptide B2A - resulted in significantly enhanced fusion rates compared to ICBG, BMP-2, or other internal control in some studies. Large heterogeneity in animal species, fusion method, and experimental groups and time points was observed across the included studies, limiting the direct comparison of the growth factors identified herein.CONCLUSIONSeveral promising investigational growth factors for spinal fusion have been identified herein; directly comparing the fusion efficacy and safety of these agents may inform clinical translation.