Three dimensional (bio)printing of blood vessels: from vascularized tissues to functional arteries.

Tissue engineering has emerged as a strategy for producing functional tissues and organs to treat diseases and injuries. Many chronic conditions directly or indirectly affect normal blood vessel functioning, necessary for material exchange and transport through the body and within tissue-engineered constructs. The interest in vascular tissue engineering is due to two reasons: (1) functional grafts can be used to replace diseased blood vessels, and (2) engineering effective vasculature within other engineered tissues enables connection with the host's circulatory system, supporting their survival. Among various practices, (bio)printing has emerged as a powerful tool to engineer biomimetic constructs. This has been made possible with precise control of cell deposition and matrix environment along with the advancements in biomaterials. (Bio)printing has been used for both engineering stand-alone vascular grafts as well as vasculature within engineered tissues for regenerative applications. In this review article, we discuss various conditions associated with blood vessels, the need for artificial blood vessels, the anatomy and physiology of different blood vessels, available 3D (bio)printing techniques to fabricate tissue-engineered vascular grafts and vasculature in scaffolds, and the comparison among the different techniques. We conclude our review with a brief discussion about future opportunities in the area of blood vessel tissue engineering.

Customizable Composite Fibers for Engineering Skeletal Muscle Models.

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multicompartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components. Textile technologies also allow control of the distribution of different cell types and the microstructure of fabricated constructs and the direction of cellular growth within the 3D microenvironment. Here, we engineered composite fibers from biocompatible cores and biologically relevant hydrogel sheaths. The fibers are mechanically robust to being assembled using textile processes and could support adhesion, proliferation, and maturation of cell populations important for the engineering of skeletal muscles. We also demonstrated that the changes in the coating of the multicompartment fibers could potentially enhance myogenesis in vitro.

3D-Printed Sugar-Based Stents Facilitating Vascular Anastomosis.

Microvascular anastomosis is a common part of many reconstructive and transplant surgical procedures. While venous anastomosis can be achieved using microvascular anastomotic coupling devices, surgical suturing is the main method for arterial anastomosis. Suture-based microanastomosis is time-consuming and challenging. Here, dissolvable sugar-based stents are fabricated as an assistive tool for facilitating surgical anastomosis. The nonbrittle sugar-based stent holds the vessels together during the procedure and are dissolved upon the restoration of the blood flow. The incorporation of sodium citrate minimizes the chance of thrombosis. The dissolution rate and the mechanical properties of the sugar-based stent can be tailored between 4 and 8 min. To enable the fabrication of stents with desirable geometries and dimensions, 3D printing is utilized to fabricate the stents. The effectiveness of the printed sugar-based stent is assessed ex vivo. The fabrication procedure is fast and can be performed in the operating room.

A Complex Cardiac Mass Originating from Interatrial Septum in a Patient with History of Kidney Cancer: A Case Report and Literature Review.

Cardiac tumors are a rare phenomenon, and most cases are secondary to metastatic cancers rather than primary tumors. Renal cell carcinoma (RCC) is notorious for metastasis to cardiac tissue. Tumor thrombus migration to the renal vein and inferior vena cava happens in up to 10% of patients with RCC. Transitional cell carcinomas are another form of renal cancer, which may metastasize to the heart and are associated with widespread metastasis. Here, we report a patient with a past medical history of metastatic transitional cell cancer of renal pelvis under treatment with checkpoint inhibitor therapy presenting with shortness of breath. He had disseminated metastasis to bones, pleural space, lungs, and muscles. A large mass was found in the interatrial septum with invasion to the right and left atrium. The mass had a cystic component protruding into the left atrium. He passed away a few days after presentation.

A Patient Presenting with Cardiac Tamponade and the Challenges of Finding Its Cause: A Cardiac Angiosarcoma.

Primary malignancies of the heart are so rare that most of the available data come from case reports or large single-center-based studies, with the overall incidence of 0.02% in the United States. Diagnosis in case of an isolated pericardial effusion as presentation is challenging, and determining that an angiosarcoma is even more challenging. Here, we presented a rare case of pericardial angiosarcoma which presented to us with tamponade. The patient eventually was diagnosed through pericardiectomy. A multimodality approach was attempted to treat the cancer. The clinical details of such a unique disease entity inspired us to present it as a case report.

Patient-Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds.

Bioprinting has emerged as a promising tool in tissue engineering and regenerative medicine. Various 3D printing strategies have been developed to enable bioprinting of various biopolymers and hydrogels. However, the incorporation of biological factors has not been well explored. As the importance of personalized medicine is becoming more clear, the need for the development of bioinks containing autologous/patient-specific biological factors for tissue engineering applications becomes more evident. Platelet-rich plasma (PRP) is used as a patient-specific source of autologous growth factors that can be easily incorporated to hydrogels and printed into 3D constructs. PRP contains a cocktail of growth factors enhancing angiogenesis, stem cell recruitment, and tissue regeneration. Here, the development of an alginate-based bioink that can be printed and crosslinked upon implantation through exposure to native calcium ions is reported. This platform can be used for the controlled release of PRP-associated growth factors which may ultimately enhance vascularization and stem cell migration.

Fas Receptor Activation by Endogenous Opioids Is A New Mechanism for Cardiomyopathy in Cirrhotic Rats.

BACKGROUND: Cirrhosis, a common consequence of chronic liver inflammation is associated with various cardiovascular dysfunctions which are called cirrhotic cardiomyopathy (CC). Among the various possible causes of CC, apoptosis is considered to have a pivotal role. OBJECTIVES: To explore the contribution of endogenous opioids in the apoptosis process in a rat model of CC. MATERIAL AND METHODS: Four genes were selected to cover both intrinsic and extrinsic pathways of apoptosis. Cardiac samples from 4 groups of rats were evaluated. Two groups were cirrhotic through bile duct ligation (BDL) receiving either naltrexone (BDL-naltrexone) or saline (BDL-saline), two others were normal rats as sham groups receiving either naltrexone (sham-naltrexone) or saline (sham-saline). Expression level of BCL2, Caspase3, Fas and FasL was explored in all groups using reverse transcriptase real-time PCR. RESULTS: BDL-saline group showed significant over-expression of BCL2, caspase3 and Fas. BCL2 expression was 1.44 (P < 0.001) and caspasse3 was 1.35 (P < 0.001) times higher than sham-saline group, Fas was also overexpressed 1.3 (P < 0.001) times higher than BDL-naltrexone group and 1.91 (P < 0.001) compared to sham-naltrexone group. Caspase3 expression was 1.35 (P < 0.001) folds higher than sham-naltrexone group. The expression pattern of FasL revealed no statistically significant change among study groups. CONCLUSION: Fas molecule enrollment during CC is a novel finding. Fas molecule is activated during cirrhosis through elevated levels of endogenous opioids. This pathway is one of the leading causes of CC. Our findings also demonstrated the protective role of naltrexone as opioids antagonist on cardiomyocytes in a rat model of CC.

Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted.

Opioid receptors blockade modulates apoptosis in a rat model of cirrhotic cardiomyopathy.

BACKGROUND: Cirrhosis is a common consequence of chronic liver inflammation is known to be associated with various manifestation of cardiovascular dysfunction, which has been introduced as a cirrhotic cardiomyopathy. Some possible pathogenic mechanisms has been reported and still more details should be explored. AIM: The present study is the first study to explore the contribution of endogenous opioids in the apoptosis process in a rat model of cirrhotic cardiomyopathy. MATERIALS AND METHODS: Cirrhosis was induced in rats by bile duct ligation (BDL) and resection. Cardiomyopathy was confirmed using trichrome staining for fibrosis. Naltrexone, an opioid antagonist was administered for 29(1) days. Apoptosis was detected using terminal transferase deoxyuridine triphosphate nick end labeling assay with some modification. Statistical evaluation of data was performed using analysis of variance test. P < 0.05 was considered to be statistically significant. RESULTS: Left ventricular (LV) wall thickness was significantly (P < 0.001) lower in the BDL group than the sham group, either receiving naltrexone or saline. No significant difference was seen in LV wall thickness or LV end diastolic diameter in BDL group receiving either saline or naltrexone. The apoptosis density of cardiac specimens of sham operated and BDL rats were dramatically different from each other. The cardiac specimens of BDL rats contained multiple apoptotic cells. In saline treated samples (BDL-saline vs. sham-saline), apoptosis density was significantly increased in BDL-saline group (P < 0.001). Cardiomyocyte apoptosis was significantly decreased in the BDL-naltrexone group compared to BDL-saline group (P < 0.001). There was no significant change in apoptosis density in sham groups receiving either naltrexone or saline. CONCLUSION: Apoptosis occurs during cirrhotic cardiomyopathy and endogenous opioid receptors blockade using naltrexone decreases its amount, but cardiac function may not be improved.

Mid-Term Follow-Up of Drug-Eluting Stenting for In-Stent Restenosis: Bare-Metal Stents versus Drug-Eluting Stents.

BACKGROUND: Despite major advances in percutaneous coronary intervention (PCI), in-stent restenosis (ISR) remains a therapeutic challenge. We sought to compare the mid-term clinical outcomes after treatment with repeat drug-eluting stent (DES) implantation ("DES sandwich" technique) with DES placement in the bare-metal stent (DES-in-BMS) in a "real world" setting. METHODS: We retrospectively identified and analyzed clinical and angiographic data on 194 patients previously treated with the DES who underwent repeat PCI for ISR with a DES or a BMS. ISR was defined, by visual assessment, as a luminal stenosis greater than 50% within the stent or within 5 mm of its edges. We recorded the occurrence of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction, and the need for target vessel revascularization (TVR). RESULTS: Of the 194 study participants, 130 were men (67.0%) and the mean ± SD of age was 57.0 ± 10.4 years, ranging from 37 to 80 years. In-hospital events (death and Q-wave myocardial infarction) occurred at a similar frequency in both groups. Outcomes at twelve months were also similar between the groups with cumulative clinical MACE at one-year follow-up of 9.6% and 11.3% in the DES-in-BMS and the DES-in-DES groups, respectively (p value = 0.702). Although not significant, there was a trend toward a higher TVR rate in the intra-DES ISR group as compared to the intra-BMS ISR group (0.9% BMS vs. 5.2% DES; p value = 0.16). CONCLUSION: Our study suggests that the outcome of the patients presenting with ISR did not seem to be different between the two groups of DES-in-DES and DES-in-BMS at one-year follow-up, except for a trend toward more frequent TVR in the DES-in-DES group. Repeat DES implantation for DES restenosis could be feasible and safe with a relatively low incidence of MACE at mid-term follow-up.

Opioid receptor antagonist promotes angiogenesis in bile duct ligated rats.

BACKGROUND AND AIM: Angiogenesis, formation of new capillaries from existing vasculature, plays a pivotal role in different pathological states such as many chronic inflammatory diseases including the chronic liver diseases. There is increasing evidence demonstrating accumulation of endogenous opioids and their role in the pathophysiology and manifestations of cholestasis, the main feature of a number of chronic progressive liver diseases. Hence, we investigated the significance of endogenous opioids in angiogenesis in an experimental model of cholestasis. METHODS: Cholestasis was induced in male Sprague-Dawley rats by bile duct ligation and resection. Naltrexone, an opioid antagonist (20 mg/kg/day) was administered to cholestatic animals for 22 +/- 1 days. The serial sections from liver tissue were stained with von Willebrand Factor antibody and micro-vessel density was assessed by calculating mean micro-vessel number in three hot spots high power microscopic fields. RESULTS: Naltrexone treatment in bile duct ligated rats led to a marked increase in the micro-vessel number (6.34 +/- 0.21 vs 5.61 +/- 0.22) (P < 0.05), which had already increased during cholestasis. CONCLUSION: In order to clarify the impacts of opioid system blockade in cirrhosis, our findings demonstrate the promoting role of opioid antagonist in angiogenesis in a rat model of cholestasis.