Freeform 3D printing of vascularized tissues: Challenges and strategies

Abstract

In recent years, freeform three-dimensional (3D) printing has led to significant advances in the fabrication of artificial tissues with vascularized structures. This technique utilizes a supporting matrix that holds the extruded printing ink and ensures shape maintenance of the printed 3D constructs within the prescribed spatial precision. Since the printing nozzle can be translated omnidirectionally within the supporting matrix, freeform 3D printing is potentially applicable for the fabrication of complex 3D objects, incorporating curved, and irregular shaped vascular networks. To optimize freeform 3D printing quality and performance, the rheological properties of the printing ink and supporting matrix, and the material matching between them are of paramount importance. In this review, we shall compare conventional 3D printing and freeform 3D printing technologies for the fabrication of vascular constructs, and critically discuss their working principles and their advantages and disadvantages. We also provide the detailed material information of emerging printing inks and supporting matrices in recent freeform 3D printing studies. The accompanying challenges are further discussed, aiming to guide freeform 3D printing by the effective design and selection of the most appropriate materials/processes for the development of full-scale functional vascularized artificial tissues.

Expanding tubular microvessels on stiff substrates with endothelial cells and pericytes from the same adult tissue

“…It can be used in tissue vascularization, which is a core question in tissue engineering. 57 For example, intensive efforts have been made to fabricate vascularized tissue and organ models, such as the vascularized pancreas, 58 , 59 adipose tissue, 60 bladder, 61 islet, 62 skin, 63 and so on. The model presented in this study can be further improved and applied in these ex vivo settings in the future.…”

“… 67 More advanced microvascular models can be made based on our method in combination with other engineering technologies, such as microfluidics, 66 electrospinning, 68 microspheres, 69 and 3D printing. 57 …”

Primary MSCs for Personalized Medicine: Ethical Challenges, Isolation and Biocompatibility Evaluation of 3D Electrospun and Printed Scaffolds

“…Complex investigations of biomimetic scaffolds for orthopedic applications are needed to finally deliver personalized cell carrying autografts to patients. Furthermore, by combining several 3D manufacturing strategies, the artificial vascularization of the constructed scaffolds could be achieved for the simultaneous reconstruction of both osseous and endothelial tissues [ 55 ].…”

Implantable Sandwich-like Scaffold/Fiber Composite Spatiotemporally Releasing Combretastatin A4 and Doxorubicin for Efficient Inhibition of Postoperative Tumor Recurrence

“…Recently, in clinical trials, mechanical and thermal means, such as the vascular clamping technique and electrotomy, have been frequently applied to prevent severe intraoperative bleeding. , Nevertheless, the bleeding in the inaccessible margins of the resection location and the long-term bleeding prevention in the postoperative process remain requesting advanced effective materials or methods. Emerging three-dimensional (3D) materials, consisting of gelatin, chitosan, sodium alginate, collagen, and so forth, with a rich porous structure, have been reported with fantastic achievements in biomedical applications. − Noteworthy, the 3D printing technique, enabling production of implantable materials, nowadays is grabbing our attention not only due to the designable shape of the personalized implant − but also because of the excellent bleeding prevention upon lyophilizing and the superior drug loading capacity. − Consequently, on the one hand, the adsorbed disseminated tumor cells confined in the pores of the 3D-printed materials diminish the high risk of distant tumor metastasis . On the other hand, the loaded chemotherapeutic drugs can further facilitate the inhibition of the tumor recurrence by eliciting the necrosis of the trapped tumor cells and the microscopic residual tumor cells in the resection margin difficult to access.…”