Abstract

Ultrasound can influence biological systems through several distinct acoustic mechanisms that can be manipulated by varying reaction conditions and acoustic exposure parameters. We recently reported a new ultrasound-based fabrication technology that exploits the ability of ultrasound to generate localized mechanical forces and thermal effects to control collagen fiber microstructure non-invasively. Exposing solutions of type I collagen to ultrasound during the period of microfibril assembly produced changes in collagen fiber structure and alignment, and increased the biological activity of the resultant collagen hydrogels. In the extracellular matrix, interactions between fibronectin and collagen fibrils influence the biological activity of both proteins. Thus, in the present study, we examined how addition of fibronectin to collagen solutions prior to ultrasound exposure affects protein organization and the biological activity of the composite hydrogels. Results indicate that ultrasound can alter the distribution of fibronectin within 3D hydrogels via thermal and non-thermal mechanisms to produce composite hydrogels that support accelerated microtissue formation. The use of acoustic energy to drive changes in protein conformation to functionalize biomaterials has much potential as a unique, non-invasive technology for tissue engineering and regenerative medicine.

Highlights

  • The development of biocompatible scaffolds that can coordinate complex, multicellular behaviors within artificial environments is essential for the development of tissue-engineered materials for a variety of research applications and clinical needs, including cutaneous healing in patients affected by chronic and hard-to-heal wounds [1,2]

  • We investigated effects of ultrasound on the structure and function of collagen and fibronectin co-polymerized within 3D hydrogels

  • The results of this study indicate that ultrasound can influence the distribution of fibronectin within 3D hydrogels via both thermal and non-thermal mechanisms to produce acoustically modified composite hydrogels that support accelerated microtissue formation

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Summary

Introduction

The development of biocompatible scaffolds that can coordinate complex, multicellular behaviors within artificial environments is essential for the development of tissue-engineered materials for a variety of research applications and clinical needs, including cutaneous healing in patients affected by chronic and hard-to-heal wounds [1,2]. A critical event during wound healing is the remodeling of the extracellular matrix (ECM) which occurs through processes of matrix proteolysis, deposition, and contraction [3,4]. Dysregulation of these tightly controlled processes occurs in many chronic illnesses including diabetes and vascular disease, and results in the failure. As many as 40–50% of patients who are treated for chronic wounds annually fail to achieve complete wound closure [6,7]

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