3D and 4D bioprinting of the heart are exciting notions in the modern era. However, myocardial bioprinting has proven to be challenging. This review outlines the methods, materials, cell types, ...issues, challenges, and future prospects in myocardial bioprinting. Advances in 3D bioprinting technology have significantly improved the manufacturing process. While scaffolds have traditionally been utilized, 3D bioprinters, which do not require scaffolds, are increasingly being employed. Improved understanding of the cardiac cellular composition and multiple strategies to tackle the issues of vascularization and viability had led to progress in this field. In vivo studies utilizing small animal models have been promising. 4D bioprinting is a new concept that has potential to advance the field of 3D bioprinting further by incorporating the fourth dimension of time. Clinical translation will require multidisciplinary collaboration to tackle the pertinent issues facing this field.
Conventional synthetic vascular grafts are limited by the inability to remodel, as well as issues of patency at smaller diameters. Tissue-engineered vascular grafts (TEVGs), constructed from ...biologically active cells and biodegradable scaffolds have the potential to overcome these limitations, and provide growth capacity and self-repair. Areas covered: This article outlines the TEVG design, biodegradable scaffolds, TEVG fabrication methods, cell seeding, drug delivery, strategies to reduce wait times, clinical trials, as well as a 5-year view with expert commentary. Expert commentary: TEVG technology has progressed significantly with advances in scaffold material and design, graft design, cell seeding and drug delivery. Strategies have been put in place to reduce wait times and improve 'off-the-shelf' capability of TEVGs. More recently, clinical trials have been conducted to investigate the clinical applications of TEVGs.
One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have ...recently developed 3D‐bioprinted biomaterial‐free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D‐bioprinted cardiac patches. The cardiac patches were generated using 3D‐bioprinting technology in conjunction with cellular spheroids created from a coculture of human‐induced pluripotent stem cell‐derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D‐bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.
Introduction and importance: Elderly and frail patients with thoracic aortic aneurysms (TAAs) near to origins of cervical arteries present facing challenges with aortic arch replacement with ...cardiopulmonary bypass, and traditional tube-type stent-grafts are also inadequate for transcatheter endovascular aortic repair (TEVAR). Thus, necessitating precise treatment with fenestrated stent-grafts from zone 0. This approach is crucial for achieving favorable postoperative outcomes without compromising activities of daily living (ADL). Case presentations: An 85-year-old-man admitted to the hospital for treatment of a large TAA. While arch replacement is a definitive procedure, it is highly invasive, and the postoperative ADL are expected to be significantly lower than preoperative levels. Therefore, we performed a debranching TEVAR from Zone 0 with fenestrated stent-graft. The patient was discharged from the hospital on the 11th postoperative day. Clinical discussion: In frail and elderly patients for whom conventional surgery may not be viable, TEVAR emerges as a preferred alternative. However, TEVAR of TAA proximal to the aortic arch continues to pose challenges, necessitating meticulous attention to the cervical branches in the intervention strategy. While surgical intervention in these patients necessitates careful consideration of its suitability, including the potential for postoperative enhancement in ADL, the use of fenestrated stent-grafts from Zone 0 emerges as one of the treatment modalities. Conclusion: We present a very elderly case in which fenestrated stent-grafts were used to avoid aortic arch replacement for a large aortic arch aneurysm, resulting in a good postoperative course with no decline in ADL.
Tissue-engineered vascular grafts (TEVGs) require adequate extracellular matrix (ECM) to withstand arterial pressure. Tissue transglutaminase (TG2) and lysyl oxidase (LOX) are enzymes that cross-link ...ECM proteins and play a pivotal role in the development of vascular stiffness associated with aging. The purpose of this study is to investigate the expression of ECM cross-linking enzymes and mechanisms of scaffold degeneration leading to vascular stiffness in TEVG remodeling. Fast- and slow-degrading electrospun TEVGs were fabricated using polydioxanone (PDO) and poly(L-lactide-co-caprolactone) (PLCL) copolymer, with a PDO/PLCL ratio of 9:1 for fast-degrading and 1:1 for slow-degrading graft. These grafts were implanted in rats (
= 5/group) as abdominal aortic interposition conduits. The grafts were harvested at 1 month to evaluate patency, mechanical properties, vascular neotissue formation, and the expression of ECM cross-linking enzymes. All TEVGs were patent without any aneurysmal formation at 1 month. ECM area, TG2-positive area, and LOX-positive area were significantly greater in fast-degrading TEVGs compared to slow-degrading TEVGs, with significantly less remaining scaffold. The mechanical properties of fast-degrading TEVGs were similar to that of native aorta, as demonstrated by strain-stress curve. In conclusion, at 1 month, fast-degrading TEVGs had rapid and well-organized ECM with greater TG2 and LOX expression and native-like mechanical properties, compared to slow-degrading TEVGs. Impact statement Around 1.4 million patients in the United States require arterial prostheses each year due to cardiovascular diseases. Current synthetic vascular grafts suffer from increased risk of infection, thrombosis, a lack of endothelialization, and compliance mismatch to the native vasculature. Tissue-engineered vascular graft (TEVGs) presented in this study exhibited tunable biodegradation profiles by controlling the polymer ratio of polydioxanone/poly(L-lactide-co-caprolactone). One month after implantation, the fast-degrading TEVGs exhibited mechanical properties similar to that of native aorta, formation of endothelium, and well-organized extracellular matrix (ECM) with increased expression of tissue transglutaminase and lysyl oxidases, which are critical to the ECM remodeling process.
Background: Unstable sternal fixation following sternotomy is one of the risk factors that affects postoperative outcomes in cardio-thoracic surgery and is associated with increased risk of ...infection, bleeding and delayed rehabilitation due to pain associated with sternal movement. Sternal plate systems, which help stabilize fixation, has been limited in use due to patients' comorbidities, such as diabetes mellitus (DM) and obesity. The conventional wire sternal-fixation procedure, which depend on years of physician' experience, raise concerns such as unstable sternal fixation due to uncompleted wire twisting. Therefore, a novel sternal-fixation procedure using both titanium cable and a PLA mesh plate was investigated as a potential improvement for sternal closure. We compared the ability of this new sternum fixation procedure (group N) against the conventional sternal fixation procedure using only a wire (group O) to achieve more stable postoperative sternal fixation. Methods and Results: Among adult open-heart surgeries performed between August 2020 and April 2023, 155 patients who underwent postoperative CT were included, with group N being the combined group and group O being the group using conventional metal wires: group N (86 patients: M 65, F 21) and group O (69 patients: M 50, F 19). Preoperative factors included age at surgery (group N: group O)=68.4±10.6 : 69.6±11.5 years (p=0.25)), BMI (group N: group O=23.0±3.7 : 24.1±7.7 (p=0.16)) and HbA1c (group N: group O=6.3±1.1 : 8.0±10.3% (p=0.10), and no factors were significantly different between the two groups. The CT analysis at the point of hospital discharge after surgery measured postoperative sternal deviation in the third rib position. Transverse displacement was significantly reduced (group N: group O=0.22±0.73: 0.83±1.08 mm (p=0.005)), and longitudinal displacement also showed an improvement but the difference was not statistically significant (group N: group O=0.53±0.86: 0.72±1.14 mm (p=0.13). Conclusion: A novel sternum closing technique using a tension-anchored titanium cable and a PLA mesh plate demonstrated improved postoperative sternal fixation in a controlled study with 155 patients. This new procedure also enables standardized stable sternal closure with a constant force without relying on conventional empirical sensation and without suppressing sternal cutting, thus contributing to the improvement of postoperative quality of life and prevention of complications.
In the ongoing search for the optimal biomaterial for tissue engineered vascular grafts (TEVGs), poly (glycerol sebacate) (PGS) has emerged as a new potential candidate. We have utilized a novel ...method to create unique, pore‐free, extruded PGS grafts with and without a supportive exterior layer of polyglycolic acid (PGA). The 1 mm diameter by 5 mm length TEVGs were implanted in a rat model of infrarenal abdominal aorta interposition grafting. Three months after implantation, TEVGs comprised of extruded PGS with an external PGA braid demonstrated a patency rate of 9/10 (90%) with no signs of dilatation, dehiscence, or rupture. The PGS/PGA graft was remodeled into a neoartery with complete endothelialization of the neoartery lumen and formation of smooth muscle actinin multilayers as demonstrated via immunohistochemistry. Formation and maturation of extracellular matrix material were also observed, with amounts of elastin and collagen comparable to native rat aorta. No significant host inflammatory response was observed. These findings suggest the combination of an extruded PGS tube with an external reinforcing PGA braid is a promising material for small diameter TEVGs.
Electrospinning is a promising technology that provides biodegradable nanofiber scaffolds for cardiovascular tissue engineering. However, success with these materials has been limited, and the ...optimal combination of scaffold parameters for a tissue-engineered vascular graft (TEVG) remains elusive. The purpose of the present study is to evaluate the effect of bone marrow mononuclear cell (BM-MNC) seeding in electrospun scaffolds to support the rational design of optimized TEVGs.
Nanofiber scaffolds were fabricated from co-electrospinning a solution of polyglycolic acid and a solution of poly(ι-lactide-co-ɛ-caprolactone) and characterized with scanning electron microscopy. Platelet activation and cell seeding efficiency were assessed by ATP secretion and DNA assays, respectively. Cell-free and BM-MNC seeded scaffolds were implanted in C57BL/6 mice (n = 15/group) as infrarenal inferior vena cava (IVC) interposition conduits. Animals were followed with serial ultrasonography for 6 months, after which grafts were harvested for evaluation of patency and neotissue formation by histology and immunohistochemistry (n = 10/group) and PCR (n = 5/group) analyses.
BM-MNC seeding of electrospun scaffolds prevented stenosis compared with unseeded scaffolds (seeded: 9/10 patent vs. unseeded: 1/10 patent, p = 0.0003). Seeded vascular grafts demonstrated concentric laminated smooth muscle cells, a confluent endothelial monolayer, and a collagen-rich extracellular matrix. Platelet-derived ATP, a marker of platelet activation, was significantly reduced after incubating thrombin-activated platelets in the presence of seeded scaffolds compared with unseeded scaffolds (p < 0.0001). In addition, reduced macrophage infiltration and a higher M2 macrophage percentage were observed in seeded grafts.
The beneficial effects of BM-MNC seeding apply to electrospun TEVG scaffolds by attenuating stenosis through the regulation of platelet activation and inflammatory macrophage function, leading to well-organized neotissue formation. BM-MNC seeding is a valuable technique that can be used in the rational design of optimal TEVG scaffolds.
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