Cardiothoracic
Repair of the Thoracic Wall With an Extracellular Matrix Scaffold in a Canine Model

https://doi.org/10.1016/j.jss.2007.04.035Get rights and content

Naturally derived extracellular matrix (ECM) scaffolds have been successfully used to promote constructive remodeling of injured or missing tissue in a variety of anatomical locations, including abdominal wall repair. Furthermore, ECM scaffolds have shown the ability to resist infection and adhesion formation. The present study investigated the utility of an ECM scaffold, specifically, porcine urinary bladder matrix (UBM), for repair of a 5 × 5 cm full-thickness lateral thoracic wall defect in a canine model (n = 6) including 5-cm segments of the 6th and 7th rib. The resected portion of the 7th rib was replaced as an interpositional graft along with the UBM scaffold. As a control, a Gore-Tex patch was used to repair the same defect (n = 2). The control animals healed by encapsulation of the Gore-Tex patch by dense collagenous tissue. The remodeled UBM grafts showed the presence of site-specific tissue, including organized fibrous connective tissue, muscle tissue, adipose tissue, and bone. Upon fluoroscopic examination, it was shown that both bony defects were replaced with new calcified bone. In the 6th rib space, new bone bridged the entire span. In the 7th rib space, there was evidence of bone formation between the interpositional graft and the existing bone, as well as de novo formation of organized bone in the shape of the missing rib segment parallel to the interpositional graft. This study shows that a naturally occurring ECM scaffold promotes site-specific constructive remodeling in a large thoracic wall defect.

Introduction

Reconstruction of the thoracic wall can be challenging when extensive resections are needed to treat primary chest wall tumors, for lung or breast tumors invading the thoracic wall, and for extensive debridements or tissue loss after traumatic injuries [1, 2, 3]. Management of the pleural space, skeletal support, and soft-tissue coverage are all required for large reconstructive efforts [4]. Current alternatives that are clinically available include autogenous grafts, vascularized muscle or omental flaps, and synthetic materials [5]. Polypropylene and polytetrafluorethylene (PTFE) meshes have been widely used to repair the chest wall in the last two decades. Composite materials including methylmethacrylate, stainless steel, and titanium with polypropylene and PTFE to provide greater stiffness have yielded composite prosthetic devices that have enabled successful reconstruction of larger defects. However, complications are common and are reported to occur in 37 to 46% of patients [5]. Morbidity can be associated with graft infection or general complications such as respiratory failure due to flail segments. Thoracic cage reconstruction in pediatric patients for congenital defects involves the additional need for sequential replacement of the prosthesis due to its inability to grow with the patient [6].

Regenerative medicine approaches using extracellular matrix (ECM) scaffolds derived from the porcine small intestinal submucosa and from human dermis (AlloDerm) have recently been reported to be effective in the treatment of patients with increased risk for mesh-related complications and for pediatric populations [6, 7, 8]. Urinary bladder matrix (UBM)-ECM scaffolds have been shown to possess antimicrobial activity [9] and promote site-specific constructive tissue remodeling in several preclinical studies, including studies of soft-tissue repair, lower urinary tract repair, and cardiovascular repair [10, 11, 12, 13, 14]. The present study evaluated the use of a UBM-ECM surgical mesh for reconstruction of a full-thickness thoracic wall defect in a canine model. It was hypothesized that the use of a degradable UBM-ECM scaffold would promote a constructive, site-appropriate tissue remodeling response with less scarring and adhesion than seen with synthetic graft materials.

Section snippets

Study Design

A 5 × 5 cm defect was created in the right thorax of 17- to 22-kg mongrel dogs (n = 8) at the level of the 6th and 7th ribs. A 5-cm length of the 6th rib was removed as part of the procedure. Similarly, a 5-cm segment of the 7th rib was resected but then sutured back in place. A small portion of the adjacent lung lobe (approximately 3 cm3) was also resected to create an intrathoracic tissue injury component to this animal model. In six dogs, the thoracic wall defect was repaired with a single

Clinical Outcomes

All dogs recovered well from the surgical procedure and had a favorable clinical outcome immediately after surgery. There was no evidence of pneumothorax, flailing, herniation, or infection. None of the dogs exhibited complications related to surgery or remodeling of the ECM scaffold prior to euthanasia at the predetermined time point.

Macroscopic Appearance

In the control animals, the Gore-Tex was encapsulated with dense fibrous tissue without adhesions at both time points. There was no evidence of bony callus

Discussion

The present study showed that a surgical mesh consisting entirely of xenogeneic ECM was able to seal an experimentally created lung injury and effectively close a large thoracic wall defect (5 × 5 cm). Constructive tissue remodeling response was facilitated and the remodeled tissue consisted of organized, site-appropriate layers of collagen, skeletal muscle, adipose tissue, and mature bone. This study showed that new bone formation can occur over the span of 5 cm when UBM-ECM is used even in

Acknowledgments

A.R.S. is employed by Acell, Inc. and has patent rights to urinary bladder matrix material, which was used in this study. Funding for the study was provided by the Department of Defense with S.F.B. as the PI. No other authors have conflicts of interest, real or apparent.

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