Abstract
The fabrication of functional tissues is essential for clinical applications such as disease treatment and drug discovery. Recent studies have revealed that the mechanical environments of tissues, determined by geometric cell patterns, material composition, or mechanical properties, play critical roles in ensuring proper tissue function. Here, we propose an acoustophoretic technique using surface acoustic waves to fabricate therapeutic vascular tissue containing a three-dimensional collateral distribution of vessels. Co-aligned human umbilical vein endothelial cells and human adipose stem cells that are arranged in a biodegradable catechol-conjugated hyaluronic acid hydrogel exhibit enhanced cell-cell contacts, gene expression, and secretion of angiogenic and anti-inflammatory paracrine factors. The therapeutic effects of the fabricated vessel constructs are demonstrated in experiments using an ischemia mouse model by exhibiting the remarkable recovery of damaged tissue. Our study can be referenced to fabricate various types of artificial tissues that mimic the original functions as well as structures.
Highlights
The fabrication of functional tissues is essential for clinical applications such as disease treatment and drug discovery
The vasculatures in the skeletal muscle primarily consist of endothelial cells (ECs) and mural cells such as pericytes or vascular smooth muscle cells
Human adipose-derived stem cell can be acquired in large numbers from human adipose tissue and expanded, which is more adequate for clinical approach
Summary
The fabrication of functional tissues is essential for clinical applications such as disease treatment and drug discovery. To overcome the limitations of existing methods and fabricate vasculatures for disease treatment, it is necessary to develop a technique that comprehensively meets the following requirements: (i) 3D cellular arrangement akin to native tissue[5], (ii) extracellular matrix (ECM) environment[3] with clinically relevant size[16], (iii) coculture of multiple cell types[17], (iv) integrated cell–cell junctions[18], and (v) composed of biocompatible, biodegradable[19], and tissue-adhesive[20] biomaterials. SSAW techniques exhibit the potential to selectively manipulate various types of microparticles[21], regulate cell–cell distances[22], and engineer cellular aggregates such as spheroids[25] Such high-resolution cell engineering is essential to replicate complex and highly ordered tissues in vivo because obtaining such tissues by current methods, including bioprinting, is difficult. Our methods and results can be applied to fabricate various types of functional tissue constructs mimicking native tissue with improved regenerative efficacy
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