Bulk Acoustic Wave Bioassembly for Precision Biofabrication of Functional Tissue Constructs

Bulk acoustic wave (BAW) bioassembly enables label‑free, contactless cell patterning, but conventional approaches are confined to simple symmetric patterns, limiting their ability to recapitulate native tissue complexity. Here we present two BAW‑based strategies to overcome this limitation. First, we rationally designed acoustic pressure fields to assemble human iPSC‑derived neural progenitors and neurons into cerebral cortex‑like microtissues with six concentric neuronal layers (~400 µm spacing), recapitulating cortical lamination. These constructs exhibited spontaneous electrophysiological activity with significantly higher firing rates and burst counts than non‑assembled controls; upon HSV‑1 infection, they developed Alzheimer’s disease‑associated pathology (Aβ deposition and neuron loss). Second, we developed soft‑lithographically defined acoustic bioassembly (SLAB), which uses a PDMS amplitude modulation template to generate arbitrary pressure distributions, enabling fabrication of both symmetric (stripes, lattices) and asymmetric bionic structures, including hepatic lobule‑like, muscle fiber, osteon, and microvessel patterns. Using SLAB, we constructed liver tissue mimics with radially arranged sinusoid‑like architectures, which showed enhanced albumin secretion, urea synthesis, glycogen storage, and lipid accumulation compared to non‑assembled controls. Our strategies are compatible with various cell types and hydrogel materials, offering flexibility for diverse tissue engineering needs. Collectively, these BAW approaches provide a versatile precision biofabrication platform for creating functional tissue constructs with native‑like geometries and improved functionality, holding promise for disease modeling, drug screening, and regenerative medicine.

Pu Chen is Professor and Chair of the Department of Biomedical Engineering, and Associate Dean of Taikang Medical School (School of Basic Medical Sciences) at Wuhan University. He serves as Principal Investigator at the Taikang Center for Life and Medical Sciences and the Cell Therapy Center of Zhongnan Hospital. He founded the Tissue Engineering and Organ Manufacturing (TEOM) Laboratory. His research focuses on innovative strategies for tissue engineering and organ manufacturing. He pioneered Faraday wave‑based bioassembly technology and developed China’s first commercial bioassembly device (CB101); he also advanced bulk acoustic wave bioassembly as a parallel biofabrication tool to bioprinting. He established multiple engineered pluripotent stem cell‑derived organoid platforms, including TGCO‑Chip, AIOMP, and 3D‑TOCP, addressing vascularization and inter‑organ crosstalk challenges. He has published over 60 papers in journals such as Advanced Materials, Advanced Science, and Engineering, with >3,000 citations, and holds >20 patents with 14 licensed for commercialization.