2013 IR&D Annual Report

Develop Transplantable Vascularized Cell Constructs to Accelerate Wound Healing, 01-R8214

Principal Investigator
Jian Ling

Inclusive Dates: 04/01/11 – 12/01/12

Background — One of the most promising treatments for both chronic and combat wounds is tissue transplantation, especially the microsurgical free-flap reconstruction. This procedure completely detaches skin and fat, including arteries and veins, called the flap, from one part of the body and moves them to the wound sites. This procedure has shown to be 95 percent successful in many wound treatments. However, free-flap reconstruction is limited by the availability of the tissue flaps from either autograft or allograft due to donor-site morbidity. The objective of this project was to develop engineered "tissue flaps" to accelerate the wound healing process.

Approach — A hybrid scaffold was developed to mimic a free flap. The hybrid scaffold was composed of a three-dimensional, cylindrical porous scaffold wrapped around a membrane material in tubular shape. The cylindrical porous scaffold is made of composite materials including polycaprolactone (PCL), collagen and fibrin. While PCL enhanced the mechanical properties of the overall scaffold for in vivo implantation, the collagen and fibrin can promote cell growth and vascular formation. The tubular-shaped membrane material formed a flexible perfusion chamber that allows the 3D scaffold to be perfused in vitro, as well as in vivo, through connections to host blood vessels. A dynamic perfusion system (see illustration) was developed to perfuse the hybrid scaffold to supply nutrition and oxygen to cells cultured on the hybrid scaffold. Traditional static culture through diffusion makes it difficult to deliver nutrition and oxygen to cells residing inside a scaffold greater than 3mm in thickness. Human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem cells (hMSCs), were co-cultured on the hybrid scaffold to convert the scaffold into a cell construct with initial vascular system.

diagram of an in vitro perfusion system
 An in vitro perfusion system to mimic blood flow to convert the hybrid scaffold to a cell contruct that mimics an engineering flap with initial vascular system before in vivo implantation.

Accomplishments — This project proposed a new idea of a tissue-engineered composite scaffold to mimic free flaps used in reconstruction surgery. The composite scaffold is expected to be implanted in vivo and directly anastomosed with host blood vessels like a free flap for wound healing. Based on preliminary data, two patent applications were submitted: "Engineered Tissue Implants and Methods of Use Thereof" and "Hybrid Tissue Scaffold For Tissue Engineering."

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Southwest Research Institute® (SwRI®), headquartered in San Antonio, Texas, is a multidisciplinary, independent, nonprofit, applied engineering and physical sciences research and development organization with 9 technical divisions.