Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, PR China; Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, PR China; "Biomanufacturing and Engineering Living Systems" Innovation International Talents Base (111 Base), Beijing, 100084, PR China.
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, PR China; Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, PR China; "Biomanufacturing and Engineering Living Systems" Innovation International Talents Base (111 Base), Beijing, 100084, PR China; Department of Mechanical Engineering, Drexel University, Philadelphia, PA, 19104, USA.
Biomaterials. 2022 Jan;280:121298. doi: 10.1016/j.biomaterials.2021.121298. Epub 2021 Nov 30.
The field of cardiac tissue engineering has advanced over the past decades; however, most research progress has been limited to engineered cardiac tissues (ECTs) at the microscale with minimal geometrical complexities such as 3D strips and patches. Although microscale ECTs are advantageous for drug screening applications because of their high-throughput and standardization characteristics, they have limited translational applications in heart repair and the in vitro modeling of cardiac function and diseases. Recently, researchers have made various attempts to construct engineered cardiac pumps (ECPs) such as chambered ventricles, recapitulating the geometrical complexity of the native heart. The transition from microscale ECTs to ECPs at a translatable scale would greatly accelerate their translational applications; however, researchers are confronted with several major hurdles, including geometrical reconstruction, vascularization, and functional maturation. Therefore, the objective of this paper is to review the recent advances on bioengineering approaches for fabrication of functional engineered cardiac pumps. We first review the bioengineering approaches to fabricate ECPs, and then emphasize the unmatched potential of 3D bioprinting techniques. We highlight key advances in bioprinting strategies with high cell density as researchers have begun to realize the critical role that the cell density of non-proliferative cardiomyocytes plays in the cell-cell interaction and functional contracting performance. We summarize the current approaches to engineering vasculatures both at micro- and meso-scales, crucial for the survival of thick cardiac tissues and ECPs. We showcase a variety of strategies developed to enable the functional maturation of cardiac tissues, mimicking the in vivo environment during cardiac development. By highlighting state-of-the-art research, this review offers personal perspectives on future opportunities and trends that may bring us closer to the promise of functional ECPs.
在过去的几十年中，心脏组织工程领域取得了进展；然而，大多数研究进展仅限于具有最小几何复杂性（如 3D 条带和贴片）的微观工程心脏组织（ECT）。尽管微尺度 ECT 由于高通量和标准化的特点，在药物筛选应用中具有优势，但它们在心修复和心脏功能及疾病的体外建模方面的转化应用有限。最近，研究人员已经尝试构建各种工程心脏泵（ECP），如腔室心室，以再现天然心脏的几何复杂性。从可转化规模的微尺度 ECT 过渡到 ECP 将极大地加速其转化应用；然而，研究人员面临着几个主要障碍，包括几何重建、血管化和功能成熟。因此，本文的目的是综述用于制造功能性工程心脏泵的生物工程方法的最新进展。我们首先回顾了制造 ECP 的生物工程方法，然后强调了 3D 生物打印技术的无与伦比的潜力。我们强调了高细胞密度的生物打印策略的关键进展，因为研究人员开始意识到非增殖性心肌细胞的细胞密度在细胞-细胞相互作用和功能收缩性能中起着关键作用。我们总结了目前在微尺度和中尺度上工程化脉管系统的方法，这对厚的心脏组织和 ECP 的存活至关重要。我们展示了各种旨在实现心脏组织功能成熟的策略，这些策略模拟了心脏发育过程中的体内环境。通过强调最先进的研究，本综述提供了对未来机遇和趋势的个人看法，这些机遇和趋势可能使我们更接近功能性 ECP 的承诺。
