HHS Public Access Author manuscript Author Manuscript
Ann Thorac Surg. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: Ann Thorac Surg. 2016 September ; 102(3): 720–727. doi:10.1016/j.athoracsur.2016.01.110.
Novel Bioresorbable Vascular Graft with Sponge Type Scaffold as a Small-Diameter Arterial Graft Tadahisa Sugiura, MD, PhDa, Shuhei Tara, MD, PhDa, Hidetaka Nakayama, PhDc, Hirotsugu Kurobe, MD, PhDa, Tai Yi, MDa, Yong-Ung Lee, PhDa, Avione Y. Lee, PhDa, Christopher K. Breuer, MDa, and Toshiharu Shinoka, MD, PhDa,b aCenter
Author Manuscript
for Cardiovascular & Pulmonary Research, Nationwide Children’s Hospital, Columbus, OH, USA bDepartment
of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA
cQOL
Research Center Laboratory, Gunze Limited, Ayabe-shi, Kyoto, Japan
Abstract Background—Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The purpose of the present study is to evaluate the feasibility of arterial bioresorbable vascular graft, which has a porous sponge type scaffold, as a small-diameter arterial conduit.
Author Manuscript
Methods—The grafts were constructed by a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (l-lactic acid) (PLA) nano-fiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 μm) or a large size (28.5 ± 5.25 μm). We compared the difference in cellular infiltration followed by tissue remodeling between the groups. The grafts were implanted in 8–10 week old female mice (n = 15 in each group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks and sacrificed to evaluate neotissue formation. Results—No aneurysmal change or graft rupture was observed in both groups. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization
Author Manuscript
*
Corresponding Author: Toshiharu Shinoka, MD, PhD, Director, Cardiovascular Tissue Engineering Program, Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, 700 Children’s Drive, T2294, Columbus, OH 43205, Phone: 614-722-3103, Fax: 614-722-3111, [email protected]. Drs Sugiura and Tara contributed equally to this work.
Drs Breuer and Shinoka discloses a financial relationship with Gunze Ltd. (Kyoto, Japan). Disclosure Statement: C.K.B and T.S receive grant support from Gunze Ltd. (Kyoto, Japan). Presented at the Fifty-second Annual Meeting of the Society of Thoracic Surgeons, Phoenix, AZ, Jan 23–27, 2016. 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.
Sugiura et al.
Page 2
Author Manuscript
with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups. Conclusions—Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high pressure arterial circulation environment. Whereas the large pore size scaffold did not improve cellular infiltration and neotissue formation when compared to the small pore scaffold. Keywords Tissue engineering; Bioresorbable vascular grafts; Small-diameter arterial grafts; Pore size; Electrospinning technique
Author Manuscript
The most pressing limitation in using autografts for cardiovascular surgeries is insufficient availability of viable tissue in patients, especially patients with widespread atherosclerotic vascular disease. For patients with viable tissue, there is often a lack of harvestable vessels due to previous cardiovascular surgical procedures [1]. If the patient has viable tissue, they must be subjected to additional surgical procedures for harvesting and preparing the tissue grafts. To alleviate these issues, prosthetic arterial grafts have arisen as a viable alternative to autologous arterial or venous substitutes required for patients with cardiovascular diseases.
Author Manuscript
Current commercialized prosthetic grafts composed of expanded-polytetrafluoroethylene or polyethylene terephthalate have arisen as a substitute and have shown promise in large blood vessels (>6mm). However, they have not yet shown clinical effectiveness for small-diameter arteries (< 6 mm) due to their poor patency rates [2]. To address this challenge, small diameter bioresorbable vascular grafts have arisen as an alternative to non-bioresorbable prosthetic grafts [3]. These bioresorbable vascular grafts are created to restore function and, over time, transform into biologically active blood vessels [4].
Author Manuscript
Bioresorbable vascular grafts are biologically active grafts which are entirely reconstituted by host-derived cells over the course of an inflammation-mediated degradation process [5]. The application of bioresorbable vascular grafts has several advantages such as growth potential, favorable biocompatibility, and low risk of infection or rejection. Clinical evidence has now shown that bioresorbable vascular grafts have had some success in limited clinical trials to use for pediatric patients undergoing extracardiac total cavopulmonary connection procedures [6, 7]. In those studies, a porous, bioresorbable sponge type scaffold composed of poly(l-lactide-co-ε-caprolactone) (PLCL) and reinforced by a mesh of poly(glycolic acid) (PGA) was successfully applied to venous circulation in a low pressure environment (
Ann Thorac Surg. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: Ann Thorac Surg. 2016 September ; 102(3): 720–727. doi:10.1016/j.athoracsur.2016.01.110.
Novel Bioresorbable Vascular Graft with Sponge Type Scaffold as a Small-Diameter Arterial Graft Tadahisa Sugiura, MD, PhDa, Shuhei Tara, MD, PhDa, Hidetaka Nakayama, PhDc, Hirotsugu Kurobe, MD, PhDa, Tai Yi, MDa, Yong-Ung Lee, PhDa, Avione Y. Lee, PhDa, Christopher K. Breuer, MDa, and Toshiharu Shinoka, MD, PhDa,b aCenter
Author Manuscript
for Cardiovascular & Pulmonary Research, Nationwide Children’s Hospital, Columbus, OH, USA bDepartment
of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA
cQOL
Research Center Laboratory, Gunze Limited, Ayabe-shi, Kyoto, Japan
Abstract Background—Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The purpose of the present study is to evaluate the feasibility of arterial bioresorbable vascular graft, which has a porous sponge type scaffold, as a small-diameter arterial conduit.
Author Manuscript
Methods—The grafts were constructed by a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (l-lactic acid) (PLA) nano-fiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 μm) or a large size (28.5 ± 5.25 μm). We compared the difference in cellular infiltration followed by tissue remodeling between the groups. The grafts were implanted in 8–10 week old female mice (n = 15 in each group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks and sacrificed to evaluate neotissue formation. Results—No aneurysmal change or graft rupture was observed in both groups. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization
Author Manuscript
*
Corresponding Author: Toshiharu Shinoka, MD, PhD, Director, Cardiovascular Tissue Engineering Program, Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, 700 Children’s Drive, T2294, Columbus, OH 43205, Phone: 614-722-3103, Fax: 614-722-3111, [email protected]. Drs Sugiura and Tara contributed equally to this work.
Drs Breuer and Shinoka discloses a financial relationship with Gunze Ltd. (Kyoto, Japan). Disclosure Statement: C.K.B and T.S receive grant support from Gunze Ltd. (Kyoto, Japan). Presented at the Fifty-second Annual Meeting of the Society of Thoracic Surgeons, Phoenix, AZ, Jan 23–27, 2016. 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.
Sugiura et al.
Page 2
Author Manuscript
with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups. Conclusions—Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high pressure arterial circulation environment. Whereas the large pore size scaffold did not improve cellular infiltration and neotissue formation when compared to the small pore scaffold. Keywords Tissue engineering; Bioresorbable vascular grafts; Small-diameter arterial grafts; Pore size; Electrospinning technique
Author Manuscript
The most pressing limitation in using autografts for cardiovascular surgeries is insufficient availability of viable tissue in patients, especially patients with widespread atherosclerotic vascular disease. For patients with viable tissue, there is often a lack of harvestable vessels due to previous cardiovascular surgical procedures [1]. If the patient has viable tissue, they must be subjected to additional surgical procedures for harvesting and preparing the tissue grafts. To alleviate these issues, prosthetic arterial grafts have arisen as a viable alternative to autologous arterial or venous substitutes required for patients with cardiovascular diseases.
Author Manuscript
Current commercialized prosthetic grafts composed of expanded-polytetrafluoroethylene or polyethylene terephthalate have arisen as a substitute and have shown promise in large blood vessels (>6mm). However, they have not yet shown clinical effectiveness for small-diameter arteries (< 6 mm) due to their poor patency rates [2]. To address this challenge, small diameter bioresorbable vascular grafts have arisen as an alternative to non-bioresorbable prosthetic grafts [3]. These bioresorbable vascular grafts are created to restore function and, over time, transform into biologically active blood vessels [4].
Author Manuscript
Bioresorbable vascular grafts are biologically active grafts which are entirely reconstituted by host-derived cells over the course of an inflammation-mediated degradation process [5]. The application of bioresorbable vascular grafts has several advantages such as growth potential, favorable biocompatibility, and low risk of infection or rejection. Clinical evidence has now shown that bioresorbable vascular grafts have had some success in limited clinical trials to use for pediatric patients undergoing extracardiac total cavopulmonary connection procedures [6, 7]. In those studies, a porous, bioresorbable sponge type scaffold composed of poly(l-lactide-co-ε-caprolactone) (PLCL) and reinforced by a mesh of poly(glycolic acid) (PGA) was successfully applied to venous circulation in a low pressure environment (
