Norris E G, Dalecki D, Hocking D C
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA.
Mater Today Bio. 2019 Jun;3. doi: 10.1016/j.mtbio.2019.100018. Epub 2019 Jul 22.
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/cm) 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.
开发具有空间保真度以重现天然细胞外基质（ECM）物理和生化特性的可调谐生物材料，对于各种生物医学、生物学和临床应用而言至关重要。多种因素使ECM蛋白——I型胶原蛋白成为一种有吸引力的生物材料，包括其易于分离、低抗原性和毒性以及可生物降解性。然而，目前的胶原蛋白凝胶配方无法重现天然组织中观察到的胶原蛋白结构范围，这在充分发挥基于胶原蛋白的生物材料的潜力方面构成了重大挑战。胶原蛋白纤维结构可在体外通过机械力、环境因素或热机制进行调控。在此，我们描述了一种基于超声的新型制造技术，该技术利用超声产生局部机械力的能力，以非侵入性方式控制胶原蛋白纤维微观结构。结果表明，在水凝胶形成过程中将可溶性胶原蛋白暴露于超声（7.8或8.8 MHz；3.2 - 10 W/cm）下，会导致胶原蛋白纤维结构和组织的局部变化，从而促进细胞迁移水平的提高。此外，多光子成像显示，超声处理而非假处理的水凝胶的细胞介导的胶原蛋白重塑增加，包括多细胞聚集体的形成、胶原纤维束收缩以及胶原杂交肽结合增加。从糖尿病小鼠获得的皮肤外植体培养物显示，超声处理而非假处理的胶原蛋白水凝胶的细胞介导重塑也有类似增强。利用与超声相关的机械力诱导胶原蛋白原纤维结构和组织的局部变化，从而使天然生物材料功能化，是一种用于组织工程和再生医学的有前景的非侵入性且无毒的技术。
