Acoustic modification of collagen hydrogels facilitates cellular remodeling.
Acoustic modification of collagen hydrogels facilitates cellular remodeling.
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胶原水凝胶的声学改性促进细胞重塑。
DOI：
10.1016/j.mtbio.2019.100018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hocking,DC
中科院分区：
文献类型：
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作者：
Norris,EG;Dalecki,D;Hocking,DC
开发能够以空间保真度再现天然细胞外基质(ECM)的物理和生化特性的可调生物材料对于各种生物医学、生物和临床应用具有重要意义。几个因素使细胞外基质蛋白-I型胶原成为一种有吸引力的生物材料，包括它易于分离，低抗原性和毒性，以及生物降解性。然而，目前的胶原凝胶配方未能概括天然组织中观察到的胶原蛋白结构范围，这对充分发挥胶原蛋白生物材料的潜力提出了巨大的挑战。胶原纤维的结构可以在体外通过机械力、环境因素或热机制来操纵。在这里，我们描述了一种新的基于超声波的制造技术，它利用超声波产生局部机械力的能力来非侵入性地控制胶原纤维的微结构。结果表明，在水凝胶形成过程中，将可溶性胶原暴露在超声波(7.8或8.8 MHz；3.2-10W/cm2)下会导致胶原纤维结构和组织的局部变化，从而支持细胞迁移水平的增加。此外，多光子成像显示，超声暴露而不是假暴露的水凝胶细胞介导的胶原重构增加，包括多细胞聚集体的形成，胶原纤维束的收缩，以及胶原杂交肽的结合增加。从糖尿病小鼠获得的皮肤外植体培养显示出类似的促进超声暴露但不暴露于假暴露的胶原水凝胶的细胞介导性重塑。利用超声产生的机械力改变局部胶原纤维的结构和组织，使天然生物材料功能化，是一种很有前途的非侵入性、无毒的组织工程和再生医学技术。
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.