Ultrasonic cavitation to prepare ECM hydrogels.,Acta Biomaterialia

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Ultrasonic cavitation to prepare ECM hydrogels.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-04-05 , DOI: 10.1016/j.actbio.2020.03.036
George S Hussey ₁ , David G Nascari ₂ , Lindsey T Saldin ₃ , Brian Kolich ₂ , Yoojin C Lee ₄ , Raphael J Crum ₂ , Salma O El-Mossier ₂ , William D'Angelo ₃ , Jenna L Dziki ₁ , Stephen F Badylak ₅

Affiliation

McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA; ECM Therapeutics, Inc., 118 Marshall Dr., Warrendale, PA 15086, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA; Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA 15261, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA 15261, USA; ECM Therapeutics, Inc., 118 Marshall Dr., Warrendale, PA 15086, USA.

Hydrogels composed of extracellular matrix (ECM) have been used as a substrate for 3D organoid culture, and in numerous preclinical and clinical applications to facilitate repair and reconstruction of a variety of tissues. However, these ECM hydrogel materials are fabricated using lengthy methods that have focused on enzymatic digestion of the ECM with an acid protease in an acidic solution; or the use of chaotropic extraction buffers and dialysis procedures which can affect native protein structure and function. Herein we report a method to prepare hydrogels from ECM bioscaffolds using ultrasonic cavitation. The solubilized ECM can be induced to rapidly self-assemble into a gel by adjusting temperature, and the material properties of the gel can be tailored by adjusting ECM concentration and sonication parameters. The present study shows that ECM bioscaffolds can be successfully solubilized without enzymatic digestion and induced to repolymerize into a gel form capable of supporting cell growth. STATEMENT OF SIGNIFICANCE: ECM hydrogels have been used in numerous preclinical studies to facilitate repair of tissue following injury. However, there has been relatively little advancement in manufacturing techniques, thereby impeding progress in advancing this technology toward the clinic. Laboratory techniques for producing ECM hydrogels have focused on protease digestion methods, which require lengthy incubation times. The significance of this work lies in the development of a fundamentally different approach whereby an ECM hydrogel is rapidly formed without the need for acidic solutions or protease digestion. The ultrasonic cavitation method described herein represents a marked improvement in rheological properties and processing time over traditional enzymatic methods, and may lend itself as a platform for large-scale manufacturing of ECM hydrogels.

中文翻译：

超声空化以制备ECM水凝胶。

由细胞外基质（ECM）组成的水凝胶已被用作3D类器官培养的底物，并已在许多临床前和临床应用中用于促进各种组织的修复和重建。但是，这些ECM水凝胶材料是使用冗长的方法制造的，这些方法的重点是在酸性溶液中用酸性蛋白酶对ECM进行酶消化。或使用离液提取缓冲液和渗析程序可能会影响天然蛋白质的结构和功能。本文中，我们报告了一种使用超声空化从ECM生物支架制备水凝胶的方法。通过调节温度，可以诱导溶解的ECM快速自组装成凝胶，并且可以通过调节ECM浓度和超声处理参数来定制凝胶的材料特性。本研究表明，ECM生物支架无需酶消化即可成功溶解，并诱导其重新聚合成能够支持细胞生长的凝胶形式。意义说明：ECM水凝胶已用于许多临床前研究中，以促进损伤后组织的修复。但是，制造技术的进步相对较少，从而阻碍了将该技术推向临床的进展。生产ECM水凝胶的实验室技术集中在蛋白酶消化方法上，这需要漫长的孵育时间。这项工作的意义在于开发出一种根本不同的方法，通过该方法可以快速形成ECM水凝胶，而无需酸性溶液或蛋白酶消化。

更新日期：2020-04-05

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