establishment-robust-reproducible-model-radiation-induced-skin-muscle

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. ...

University of Pittsburgh

Tissue decellularization for generating extracellular matrices has become a staple of regenerative medicine in the recent decades, extending from the research setting to clinical usage. Although methods and protocols for tissue decellularization are abundant throughout the literature, they can be time intensive and typically require specific overhead in terms of equipment. To reduce these barriers to entry, a functional and reproducible prototype of a tissue infusion/perfusion device (TIPD) has been designed and fabricated using three-dimensional printed parts in conjunction with commercially available components. This TIPD forms a system composed of two peristaltic pumps, two 3-way valves, and a chamber in which tissue is contained, and is controlled by user-customizable software. To increase repeatability among decellularization protocols, an automation function has been integrated into the software, which is able to specify fluid flow rates and define specific valve locations enabling selection of solutions to be introduced into a scaffold over the course of a decellularization process. The prototype has been tested for proof of concept through infusion and perfusion decellularization of skeletal muscle and intact kidneys, respectively, and has shown successful removal of cellular content while maintaining an intact ultrastructure. In an effort to increase the reproducibility of experimental designs and to promote an open source hardware initiative in the field of tissue engineering, a novel device was conceptualized and prototyped with printable part files made available for its fabrication in tandem with instructions for assembly. Impact Statement Repeatable methods for decellularization are essential for achieving consistent substrates between batches, laboratories, and facilities. To meet this end, an automatable tissue infusion/perfusion device composed of three-dimensional printed parts and commercially available components has been prototyped and tested. Materials and instructions for its assembly have been made available in an effort to reduce variability among equipment as well as to provide a platform on which to iterate open-source hardware in tissue engineering.

Design and Fabrication of an Automatable, 3D Printed Perfusion Device for Tissue Infusion and Perfusion Engineering.

Peripheral nerve injury and the associated muscle atrophy has an estimated annual healthcare burden of $150 billion dollars in the United States. When considering the total annual health-related spending of $3.5 trillion, these pathologies alone occupy about 4.3%. The prevalence of these ailments is rooted, at least in part, in the lack of specific preventative therapies that can be administered to muscle while it remains in the denervated state. To address this, skeletal muscle-derived ECM (skECM) was injected directly in denervated muscle with postoperative analysis performed at 20 weeks, including gait analysis, force production, cytokine quantification, and histological analysis. skECM was shown to be superior against non-injected muscle controls showing no difference in contraction force to uninjured muscle at 20 weeks. Cytokines IL-1β, IL-18, and IFNγ appeared to mediate regeneration with statistical regression implicating these cytokines as strong predictors of muscle contraction, showing significant linear correlation.

Jocelyn S. Baker

Department of Plastic Surgery

University of Pittsburgh

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Jocelyn S. Baker

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Plastic Surgery

University of Pittsburgh

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis

Department of Plastic Surgery