A newly published article from Dr. Hocking’s Lab used F-CHPs to image collagen remodeling due to acoustic disturbance. They found that exposing the collagen hydrogels to ultrasound waves revealed areas of cell-mediated collagen fiber remodeling. These areas of collagen remodeling were corroborated with SHG imaging. These results indicate that ultrasound exposure does not directly alter triple-helical conformation of collagen, but sensitizes the collagen to cellular remodeling. In the accompanying figure, they saw that hydrogels polymerized with cells and under ultrasound exposure resulted in higher levels of collagen remodeling (A, +cells) compared to an acellular environment (A, -cells). They also evaluated collagen remodeling in a sham model without ultrasound and saw that the collagen remodeling was similar with or without cells (B).

Abstract: Developing tunable biomaterials that have the capacity to recreate the physical and biochemical characteristics of native extracellular matrices (ECMs) with spatial fidelity is important for a variety of biomedical, biological, and clinical applications. Several factors have made the ECM protein, collagen I, an attractive biomaterial, including its ease of isolation, low antigenicity and toxicity, and biodegradability. However, current collagen gel formulations fail to recapitulate the range of collagen structures observed in native tissues, presenting a significant challenge in achieving the full potential of collagen-based biomaterials. Collagen fiber structure can be manipulated in vitro through mechanical forces, environmental factors, or thermal mechanisms. Here, we describe a new ultrasound-based fabrication technology that exploits the ability of ultrasound to generate localized mechanical forces to control the collagen fiber microstructure non-invasively. The results indicate that exposing soluble collagen to ultrasound (7.8 or 8.8 ​MHz; 3.2–10 ​W/cm2) during hydrogel formation leads to local variations in collagen fiber structure and organization that support increased levels of cell migration. Furthermore, multiphoton imaging revealed increased cell-mediated collagen remodeling of ultrasound-exposed but not sham-exposed hydrogels, including formation of multicellular aggregates, collagen fiber bundle contraction, and increased binding of collagen hybridizing peptides. Skin explant ​cultures obtained from diabetic mice showed similar enhancement of cell-mediated remodeling of ultrasound-exposed but not sham-exposed collagen hydrogels. Using the mechanical forces associated with ultrasound to induce local changes in collagen fibril structure and organization ​to functionalize native biomaterials is a promising non-invasive and non-toxic technology for tissue engineering and regenerative medicine.


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