Center for Control of Inflammation and Tissue Repair

Investigators:

Margaret Allen, MD, FACS, Dr. Sc., Research Member, Program Director
Thomas Wight, PhD, Member and Director, Hope Heart Program
Robert Vernon, PhD, Research Associate Member
Gerald Nepom, MD, PhD, Member and Director, BRI

Laboratories:

Allen Laboratory
Wight Laboratory
Vernon Laboratory
Nepom Laboratory

The Center for Control of Inflammation and Tissue Repair (CITR) at the Benaroya Research Institute is comprised of immunologists, extracellular matrix biologists, tissue engineers, and transplant surgeons working together to develop new therapies for conservation, repair, and reconstruction of traumatically-injured tissues, with the goal of maximizing recovery of tissue function. The CITR research team is developing new therapies to improve cell survival in the first hours after injury and new, engineered tissues to repair or replace tendons, ligaments, muscles, and blood vessels. Uniquely, these engineered tissues will be constructed from natural biological materials and, ultimately, will incorporate the patient’s own cells to avert tissue rejection.

CITR researchers are working in the new, exciting field of ‘tissue engineering’, which combines structurally supportive materials (referred to as ‘scaffolds’) with cells to create tissue replacements that have the form and function of the body’s natural tissue. In contrast to the plastics and metals used in traditional prostheses, the central focus of CITR research is the use of extracellular matrix – the natural substance that holds cells together in every tissue – as scaffolds for tissue replacements. The CITR team is developing engineered tissues that incorporate special forms of extracellular matrix that provide natural elasticity, help cells organize properly, control tissue rejection, and limit scar formation. In addition to creating replacements for lost tissue, the CITR is developing techniques to conserve tissue that remains at the site of traumatic injury. For example, methods that promote the vitality of transplanted organs and the survival of heart muscle after heart attack are being adapted by CITR researchers to preserve skeletal muscle at the site of major limb injuries.

The goal of the CITR program is not limited to basic research, but rather is focused on deliverable medical devices and therapies to provide new solutions for patients and loved ones who are faced with the prospect of losing a limb or life-sustaining tissue. To this end, Benaroya Research Institute is positioned to move advances from the laboratory toward therapies for patients through an approach referred to as translational research. This ‘bench to bedside’ method is accomplished in partnership with physicians and staff at the Virginia Mason Medical Center, who are experienced in applying breakthroughs in basic science to patient care through controlled clinical trials.

Figure 1. Production of engineered tissue prototypes. A) An engineered prototype of a blood vessel wall (arrow) is comprised of a natural collagen scaffold populated with vascular smooth muscle cells. B) An engineered ligament prototype (arrow) is viewed from above. Like the blood vessel prototype shown in panel A, the ligament prototype is comprised of a collagen scaffold populated with cells, which are fibroblasts in this specimen.

Figure 2. Production of elastic material in an engineered blood vessel prototype. A cross-section of the wall of a typical engineered blood vessel (A) has only sparse, scattered elastic material (black stain). In contrast, the wall of an engineered blood vessel made with technologies developed within the CITR (B) contains layers rich in elastic material (arrows). In mechanical tests, this vessel was substantially stronger and more elastic than the vessel shown in A.

Figure 3. Using growth factor signals in a natural collagen matrix scaffold to grow new vessels in an area without a blood supply – the first step to a “smart bandage.” A collagen gel scaffold incorporating a natural stimulant for blood vessel growth was implanted into a model. After 7 days, blood vessels began to sprout within the implant (A – arrows). After 14 days, a well-formed network of new blood vessels had formed (B – arrow). Similar approaches can be applied to improve the vascularization of wounds and engineered tissue implants.