Bovine pericardium is widely used in surgery and is commonly used for a patch after arteriotomy during cardiovascular surgery. Bovine pericardial patches have several advantages compared to prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding and possibly reduced rates of infection. These advantages of bovine pericardium have led to its common use during carotid endarterectomy. However, long-term clinical results reported after carotid endarterectomy have suggested several issues that may be related to the patch including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification and thrombosis. These complications may diminish the long-term efficacy of carotid endarterectomy and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which bovine pericardium heals after patch angioplasty may lead to next generation tissue engineered patches.Bovine pericardium (BP) has come into common clinical use during the past 20 years, especially when used as a patch for arterial closure during vascular and cardiac surgery. Bovine pericardial patches possess many technical merits that have led to their widespread adoption in the operating room, including easy handling, less suture bleeding and the ability to immediately perform arterial duplex examination at the site of angioplasty. However, long-term results of this biomaterial are poorly documented and need cautious interpretation as to whether its long term performance is related to the material itself or to the operation in which it is used. For example, it is unclear whether restenosis after carotid endarterectomy is directly related to the patch itself or whether restenosis is an inevitable consequence of the arterial procedure. In addition, there are sporadic reports of unusual complications with BP patches, including patch rupture and cartilaginous metaplasia. Although these reports are Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. unusual, careful examination of these potential areas of improvement may lead to future generations of BP patches with superior performance. NIH Public AccessThe native structure of bovine pericardium has three layers: 1) the serosa, the inner thin layer consisting of mesothelial cells; 2) the fibrosa, the thicker layer formed by diversely oriented, wavy bundles of collagen and elastin; and 3) the epipericardial connective tissue layer, the outer layer that is partly continuous with the pericardiosternal ligaments. Commercially available patches are processed to be acellular, preventing transpl...

Introduction Several clinical trials are currently evaluating stem cell therapy for patients with critical limb ischemia that have no other surgical or endovascular options for revascularization. However, these trials are conducted with different protocols, including use of different stem cell populations and different injection protocols, providing little means to compare trials and guide therapy. Accordingly, we developed a murine model of severe ischemia to allow methodical testing of relevant clinical parameters. Methods High femoral artery ligation and total excision of the superficial femoral artery (SFA) was performed on C57BL/6 mice. MNC were isolated from the bone marrow of donor mice, characterized using FACS, and injected (5×105−2×106) into the semimembranosus (proximal) or gastrocnemius (distal) muscle. Vascular and functional outcomes were measured using invasive Doppler, laser Doppler perfusion imaging, and the Tarlov and ischemia scores. Histological analysis included quantification of muscle fiber area and number as well as capillary density. Results Blood flow and functional outcomes were improved in MNC-treated mice as compared to controls over 28 days (Flow: P < .0001; Tarlov: P = .0004; ischemia score: P = .0002). MNC-treated mice also showed greater gastrocnemius fiber area (P = .0053) and increased capillary density (P = .0004). Dose-response analysis showed increased angiogenesis and gastrocnemius fiber area but no changes in macroscopic vascular flow or functional scores. Mice injected proximally to the ischemic area had overall similar functional outcomes to mice injected more distally, but increased muscle flow, capillary density, and gastrocnemius fiber area (P < .05). Conclusions High femoral ligation with complete excision of the SFA is a reliable model of severe hind limb ischemia in C57BL/6 mice that shows a response to MNC-treatment for both functional and vascular outcomes. A dose response to MNC injection appears to be present, at least microscopically, suggesting that an optimal cell number for stem cell therapy exists and that preclinical testing needs to be performed to optimally guide human trials. Injection of MNC proximal to the site of ischemia may provide some different outcomes compared to distal injection and warrants additional study.

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