Over the past years, the fabrication of adequate vascular networks has remained the main challenge in engineering tissues due to technical difficulties, while the ultimate objective of tissue engineering is to create fully functional and sustainable organs and tissues to transplant in the human body. There have been a number of studies performed to overcome this limitation, and as a result, 3D printing has become an emerging technique to serve in a variety of applications in constructing vascular networks within tissues and organs. 3D printing incorporated technical approaches allow researchers to fabricate complex and systematic architecture of vascular networks and offer various selections for fabrication materials and printing techniques. In this review, we will discuss materials and strategies for 3D printed vascular networks as well as specific applications for certain vascularized tissue and organ regeneration. We will also address the current limitations of vascular tissue engineering and make suggestions for future directions research may take.Copyright © 2019 Elsevier Inc. All rights reserved.

One of the pivotal factors that limits the clinical applications of tissue engineering is the inability to create complex three-dimensional (3D) tissues due to the lack of a long-range mass transport capability. Here we present a simple versatile strategy to fabricate perfusable and permeable hierarchical microchannel-networks (PHMs) via the combination of one-pot 3D printed sacrificial caramel templates and polymer coating with integrated phase separation. The patterned PHMs possess a biomimetic three level vascular structure including a custom-made scalable 3D framework, interconnected microchannels and permeable walls with controllable micropores. The fabrication process can be adapted to various polymers and integrated with diverse matrices including hydrogels, particle leached porous scaffolds, electrospun nanofibers, and bacterial cellulose. We demonstrated the power of PHMs to facilitate mass exchange in tissue engineering constructs by showing that the PHMs could maintain the metabolic functions of heart cells in vitro, facilitate in vivo angiogenesis and tissue integration, and efficiently treat myocardial infarction.

Though in vivo models provide the most physiologically relevant environment for studying tissue function, in vitro studies provide researchers with explicit control over experimental conditions and the potential to develop high throughput testing methods. In recent years, advancements in developmental biology research and imaging techniques have significantly improved our understanding of the processes involved in vascular development. However, the task of recreating the complex, multi-scale vasculature seen in in vivo systems remains elusive.3D bioprinting offers a potential method to generate controlled vascular networks with hierarchical structure approaching that of in vivo networks. Bioprinting is an interdisciplinary field that relies on advances in 3D printing technology along with advances in imaging and computational modeling, which allow researchers to monitor cellular function and to better understand cellular environment within the printed tissue.As bioprinting technologies improve with regards to resolution, printing speed, available materials, and automation, 3D printing could be used to generate highly controlled vascularized tissues in a high throughput manner for use in regenerative medicine and the development of in vitro tissue models for research in developmental biology and vascular diseases.© 2015 Wiley Periodicals, Inc.

Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.Published by Elsevier Ltd.

Until recent, there are no ideal small diameter vascular grafts available on the market. Most of the commercialized vascular grafts are used for medium to large-sized blood vessels. As a solution, vascular tissue engineering has been introduced and shown promising outcomes. Despite these optimistic results, there are limitations to commercialization. This review will cover the need for extrusion-based 3D cell-printing technique capable of mimicking the natural structure of the blood vessel. First, we will highlight the physiological structure of the blood vessel as well as the requirements for an ideal vascular graft. Then, the essential factors of 3D cell-printing including bioink, and cell-printing system will be discussed. Afterwards, we will mention their applications in the fabrication of tissue engineered vascular grafts. Finally, conclusions and future perspectives will be discussed.© 2022. The Author(s).

Joint replacements have proved a medical success providing symptomatic relief and return to mobility in many patients with arthritis. However, multiple revision surgeries due to joint failure can result in complex revision scenarios with significant bone tissue loss, in an elderly population, which poses a significant clinical challenge. Computer-aided design-computer-assisted manufacturing (CAD-CAM) prototyped bespoke implants are currently being used as an alternative and innovative approach for joint restoration in salvage cases, while the incorporation of autologous skeletal stem cells to optimize regenerative capacity can enhance implant osseointegration. We present a case series of 11 patients with severe disability and significant bone loss due to failed joint replacements. The choice of CAD-CAM prototyped joint implants enhanced with autologous skeletal stem cells resulted in significant patient-reported clinical and radiological improvements.

Biomanufacturing of tissues/organs is our big dream, driven by two needs: organ transplantation and accurate tissue models. Over the last decades, 3D bioprinting has been widely applied in the construction of many tissues/organs such as skins, vessels, hearts,, which can not only lay a foundation for the grand goal of organ replacement, but also be served as models committed to pharmacokinetics, drug screening and so on. As organs are so complicated, many bioprinting methods are exploited to figure out the challenges of different applications. So the question is how to choose the suitable bioprinting method? Herein, we systematically review the evolution, process and classification of 3D bioprinting with an emphasis on the fundamental printing principles and commercialized bioprinters. We summarize and classify extrusion-based, droplet-based, and photocuring-based bioprinting methods and give some advices for applications. Among them, coaxial and multi-material bioprinting are highlighted and basic principles of designing bioinks are also discussed.© 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V.

Electrospun nanofibrous scaffolds show great application potentials for wound healing owing to their effective simulation of extracellular matrix (ECM). Three-dimensional (3D) nanofibrous dressings exhibit relatively high specific surface areas, better mimicry of native ECM, adjustable hydrophilicity and breathability, good histocompatibility, enhanced wound healing, and reduced inflammation. In the present work, we designed the 3D polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) nanofibrous scaffolds by an electrospinning and gas foaming process. Then, gelatin and heparin (Gel/Hep) were assembled onto the surface of PCL/PCS nanofibers by electrostatic adsorption, and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into Gel/Hep layer to form a multifunctional 3D nanofibrous scaffold (PCL/PCS@Gel/Hep+VEGF) for accelerating wound healing. The as-fabricated 3D PCL/PCS@GEL/Hep+VEGF nanofibrous scaffold showed excellent antibacterial ability, hemocompatibility and biocompatibility in vitro and wound healing ability in vivo. Immunological analysis showed that the as-fabricated nanofibrous scaffold inhibited inflammation at the wound sites while promoting angiogenesis during the wound healing process. STATEMENT OF SIGNIFICANCE: The electrospun 3D fibrous scaffolds using polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) have been fabricated as backbone for mimicking the extracellular matrix (ECM). Gelatin and heparin (Gel/Hep) were wrapped onto the surface of PCL/PCS fibers by electrostatic adsorption and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into surface Gel/Hep layer to form multifunctional 3D fibrous scaffolds. The as-fabricated multifunctional 3D fibrous scaffolds with good antibacterial ability and biocompatibility have been used as dressings for accelerating wound healing by inhibiting inflammation at the wound sites while promoting angiogenesis during the wound healing process.Copyright © 2022. Published by Elsevier Ltd.

Angiogenesis is touted as a fundamental procedure in the regeneration and restoration of different tissues. The induction of de novo blood vessels seems to be vital to yield a successful cell transplantation rate loaded on various scaffolds. Scaffolds are natural or artificial substances that are considered as one of the means for delivering, aligning, maintaining cell connection in a favor of angiogenesis. In addition to the potential role of distinct scaffold type on vascularization, the application of some strategies such as genetic manipulation, and conjugation of pro-angiogenic factors could intensify angiogenesis potential. In the current review, we focused on the status of numerous scaffolds applicable in the field of vascular biology. Also, different strategies and priming approaches useful for the induction of pro-angiogenic signaling pathways were highlighted.

This paper aims to evaluate the mechanical behaviour of a bioresorbable polymeric coronary scaffold using finite element method, focusing on scaffold-artery interaction during degradation and vessel remodelling. A series of nonlinear stress-strain responses was constructed to match the experimental measurement of radial stiffness and strength for polymeric scaffolds over 2-year in-vitro degradation times. Degradation process was modelled by incorporating the change of material property as a function of time. Vessel remodelling was realised by changing the size of artery-plaque system manually, according to the clinical data in literature. Over degradation times, stress on the scaffold tended to increase firstly and then decreased gradually, corresponding to the changing yield stress of the scaffold material; whereas the stress on the plaque and arterial layers showed a continuous decrease. In addition, stress reduction was also observed for scaffold, plaque and artery in the simulations with the consideration of vessel remodelling. For the first time, the work offered insights into mechanical interaction between a bioresorbable scaffold and blood vessel during two-year in-vitro degradation, which has significance in assisting with further development of bioresorbable implants for treating cardiovascular diseases.Copyright © 2017 Elsevier Ltd. All rights reserved.

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O generated by CaO nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation, as well as angiogenesis and osteogenic differentiation with the assistance of Zn. More significantly, the synergy of O and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.© 2024 The Authors.

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.

Cranial defects usually occur after trauma, neurosurgical procedures like decompressive craniotomy, tumour resections, infection and congenital defects. The purpose of cranial vault repair is to protect the underlying brain tissue, to reduce any localized pain and patient anxiety, and improve cranial aesthetics. Cranioplasty is a frequent neurosurgical procedure achieved with the aid of cranial prosthesis made from materials such as: titanium, autologous bone, ceramics and polymers. Prosthesis production is often costly and requires complex intraoperative processes. Implant customized manufacturing for craniopathies allows for a precise and anatomical reconstruction in a shorter operating time compared to other conventional techniques. We present a simple, low-cost method for prosthesis manufacturing that ensures surgical success.Two patients with cranial defects are presented to describe the three-dimensional (3D) printing technique for cranial reconstruction. A digital prosthesis model is designed and manufactured with the aid of a 3D computed tomography. Both the data of large sized cranial defects and the prosthesis are transferred to a 3D printer to obtain a physical model in poly-lactic acid which is then used in a laboratory to cast the final customised prosthesis in polymethyl methacrylate (PMMA).A precise compliance of the prosthesis to the osseous defect was achieved. At the 6 month postoperative follow-up no complications were observed i.e. rejection, toxicity, local or systemic infection, and the aesthetic change was very significant and satisfactory. Customized 3D PMMA prosthesis offers cost advantages, a great aesthetic result, reduced operating time and good biocompatibility.

Current techniques for tissue engineering blood vessels are not customizable for vascular size variation and vessel wall thickness. These critical parameters vary widely between the different arteries in the human body, and the ability to engineer vessels of varying sizes could increase capabilities for disease modeling and treatment options. We present an innovative method for producing customizable, tissue engineered, self-organizing vascular constructs by replicating a major structural component of blood vessels - the smooth muscle layer, or tunica media. We utilize a unique system combining 3D printed plate inserts to control construct size and shape, and cell sheets supported by a temporary fibrin hydrogel to encourage cellular self-organization into a tubular form resembling a natural artery. To form the vascular construct, 3D printed inserts are adhered to tissue culture plates, fibrin hydrogel is deposited around the inserts, and human aortic smooth muscle cells are then seeded atop the fibrin hydrogel. The gel, aided by the innate contractile properties of the smooth muscle cells, aggregates towards the center post insert, creating a tissue ring of smooth muscle cells. These rings are then stacked into the final tubular construct. Our methodology is robust, easily repeatable and allows for customization of cellular composition, vessel wall thickness, and length of the vessel construct merely by varying the size of the 3D printed inserts. This platform has potential for facilitating more accurate modeling of vascular pathology, serving as a drug discovery tool, or for vessel repair in disease treatment.Copyright © 2015 Elsevier Inc. All rights reserved.

3D打印技术是一种快速兴起的新型数字化制造技术，因具有设计自由、大规模定制以及快速原型制造等优点，在医学、航天、汽车、食品等领域应用前景广阔。随着精准化、个性化医疗需求的增长，3D打印技术逐渐被应用到医疗领域，如植入物制造、诊断平台和药物输送系统等，并成为目前较为前沿的研究领域之一，其个性化定制的特点使得3D打印技术能够根据患者的病情制备相应的医疗产品以帮助患者康复。因此，本文概述了3D打印技术的发展，分类介绍了可用于3D打印的医用材料，以及3D打印技术在医疗领域的应用。但是3D打印的植入物是静态的，无生命的，不能随着内环境的变化进行适应性调整，4D打印可以制造出具有"活性"且结构更为复杂的、与天然组织结构非常相似的工程化组织结构，其继承了3D打印技术优点的同时，弥补了现有3D打印的一些缺陷，未来在医学领域会有更广阔的应用前景。

Bioprinting is the assembly of three-dimensional (3D) tissue constructs by layering cell-laden biomaterials using additive manufacturing techniques, offering great potential for tissue engineering and regenerative medicine. Such a process can be performed with high resolution and control by personalized or commercially available inkjet printers. However, bioprinting's clinical translation is significantly limited due to process engineering challenges. Upstream challenges include synthesis, cellular incorporation, and functionalization of "bioinks," and extrusion of print geometries. Downstream challenges address sterilization, culture, implantation, and degradation. In the long run, bioinks must provide a microenvironment to support cell growth, development, and maturation and must interact and integrate with the surrounding tissues after implantation. Additionally, a robust, scaleable manufacturing process must pass regulatory scrutiny from regulatory bodies such as U.S. Food and Drug Administration, European Medicines Agency, or Australian Therapeutic Goods Administration for bioprinting to have a real clinical impact. In this review, recent advances in inkjet-based 3D bioprinting will be presented, emphasizing on biomaterials available, their properties, and the process to generate bioprinted constructs with application in medicine. Current challenges and the future path of bioprinting and bioinks will be addressed, with emphasis in mass production aspects and the regulatory framework bioink-based products must comply to translate this technology from the bench to the clinic.© 2019 Wiley Periodicals, Inc.

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.).