The persistent shortage of donor-organs for transplantation and accurate tissue models for disease study has resulted in a high demand for artificial tissues and organs. The field of biofabrication steers efforts into building 3D-tissue scaffolds by applying a combination of cells, biomaterials and engineering methods. Although researchers have successfully fabricated various tissue-like constructs in the past, these models often only comprise of a single cell type and are vastly oversimplified. In comparison, native tissues in the human body consist of a wide variety of cells that perform diverse functions and are housed in complex cell-specific microenvironments. Therefore, employing biofabrication techniques for systematically mimicking the complexity and heterogeneity of native tissues is a substantial challenge. This review introduces novel advanced biofabrication techniques that are classified as either top-down or bottom-up processes and reports comprehensive strategies for generating artificial heterogeneous tissues in vitro. Analogous to nanofabrication in practice, in biofabrication, top-down strategies seek to first develop 3D porous scaffolds via techniques such as multi-nozzle extrusion and hybrid bioprinting, followed by the seeding of cells for tissue growth. Conversely, bottom-up strategies involve the assembly of different building block units that include; droplets, microtubes and cell sheets, via molding, weaving, tunneling, stacking and rolling into complex 3D tissue structures. The review outlines the strengths and shortcomings of each of these approaches and provides the reader with an in-depth prospectus and overview of future opportunities in this rapidly progressing field.

供体器官的持续缺乏和用于疾病研究的精确组织模型导致对人造组织和器官的高需求。生物制造领域通过结合细胞，生物材料和工程方法，致力于构建3D组织支架。尽管研究人员过去已经成功地制造了各种组织样结构，但是这些模型通常仅包含单个细胞类型，并且大大简化了。相比之下，人体的天然组织由执行各种功能的各种细胞组成，并被容纳在复杂的特定于细胞的微环境中。因此，采用生物制造技术来系统地模拟天然组织的复杂性和异质性是一个巨大的挑战。自上而下或自下而上的过程，并报告了在体外生成人工异种组织的综合策略。与实践中的纳米加工类似，在生物加工中，自上而下的策略旨在首先通过多喷嘴挤出和混合生物印刷等技术开发3D多孔支架，然后为组织生长播种细胞。相反，自下而上的策略涉及组装不同的构建单元，包括：液滴，微管和细胞片，通过模制，编织，隧穿，堆叠和滚动成复杂的3D组织结构。这篇综述概述了每种方法的优点和缺点，并为读者提供了深入的招股说明书，并概述了这个快速发展领域中的未来机会。