Extracellular Matrix Patches for Endarterectomy Repair

Abstract

Patch repair is the preferred method for arteriotomy closure following femoral or carotid endarterectomy. Choosing among available patch options remains a clinical challenge, as current evidence suggests roughly comparable outcomes between autologous grafts and synthetic and biologic materials. Biologic patches have potential advantages over other materials, including reduced risk for infection, mitigation of an excessive foreign body response, and the potential to remodel into healthy, vascularized tissue. Here we review the use of decellularized extracellular matrix (ECM) for cardiovascular applications, particularly endarterectomy repair, and the capacity of these materials to remodel into native, site-appropriate tissues. Also presented are data from two post-market observational studies of patients undergoing iliofemoral and carotid endarterectomy patch repair as well as one histologic case report in a challenging iliofemoral endarterectomy repair, all with the use of small intestine submucosa (SIS)-ECM. In alignment with previously reported studies, high patency was maintained, and adverse event rates were comparable to previously reported rates of patch angioplasty. Histologic analysis from one case identified constructive remodeling of the SIS-ECM, consistent with the histologic characteristics of the endarterectomized vessel. These clinical and histologic results align with the biologic potential described in the academic ECM literature. To our knowledge, this is the first histologic demonstration of SIS-ECM remodeling into site-appropriate vascular tissues following endarterectomy. Together, these findings support the safety and efficacy of SIS-ECM for patch repair of femoral and carotid arteriotomy.

Keywords: atherosclerosis; biologic patch; cerebrovascular disease; endarterectomy; extracellular matrix; peripheral arterial disease; tissue integration; tissue regeneration.

Figure 1

Schematic representation of repeated iliofemoral endarterectomies in the histologic case study. At the initial surgery, a SIS-ECM patch was placed in the common femoral artery (CFA) following removal of the atheroma. The second surgery was conducted 16 months later due to progression of disease distal to the previous SIS-ECM repair. Following endarterectomy, a Y-shaped SIS-ECM patch was placed at the branching of the CFA, profunda femoral artery, and superficial femoral artery. The previous SIS-ECM patch remained widely patent. The final surgery, a femoral-to-above-knee popliteal artery bypass, was conducted at 20 months after the index procedure due to progression of distal disease. Both previously placed SIS-ECM patches remained widely patent. At this time, a biopsy of the original SIS-ECM patch, including the area of anastomosis between the patch and the native artery, was obtained for histologic analysis.

Figure 2

Initial patch angioplasty of the common femoral artery using an SIS-ECM patch (arrow) following endarterectomy.

Figure 3

After 16 months, the SIS-ECM patch previously placed in the right common femoral artery (CFA) (arrow) was found to be completely incorporated into native vascular tissue.

Figure 4

Following progression of distal disease 20 months after the index procedure, a third operation was performed with creation of a right femoral to above-knee popliteal artery bypass. At this time, the two previous SIS-ECM patches in the common femoral artery appeared to be completely incorporated into the native femoral system (arrows). A specimen, including the anastomosis between the patch and the endarterectomized artery, was removed for histologic evaluation (dashed outline).

Figure 5

Haematoxylin and eosin-stained sections (A–C) and Masson's trichrome stained section (D) from SIS-ECM graft explanted from the common femoral artery. (A) Full field of view; a black dashed box marks an area of remnant graft material, and asterisks (*) denote intact suture holes. An area of interest is highlighted with a white dashed box which represents remodeled graft. (B) Detailed view of a full thickness section of remnant graft material undergoing active remodeling (top of the image), surrounded by organized collagen (bottom of the image). (C) Detailed view of the area of interest; a full thickness section of the remodeled graft, with no evidence of the originally implanted ECM material remaining. The more luminal side of the graft (top of the image) shows well organized and aligned collagen, minimal cellularity, and no evidence of inflammation. The more abluminal surface (bottom of the image) shows slightly less organized collagenous connective tissue, moderate, and localized cellularity consistent with residual remodeling, and no evidence of active inflammation or necrosis. The collagenous tissue shows a population of morphologically normal spindle cells, which are most likely fibroblasts. (D) Detailed view of trichrome stained tissue representing a remodeled ECM area showing well organized, dense accumulation of collagen. The tissue was aligned in a circumferential fashion, as would be expected for a normal blood vessel. Small areas of red staining represent islets of smooth muscle.