Development of a fibrin composite-coated poly(epsilon-caprolactone) scaffold for potential vascular tissue engineering applications.

Poor cell adhesion, cytotoxicity of degradation products and lack of biological signals for cell growth, survival, and tissue generation are the limitations in the use of a biodegradable polymer scaffold for vascular tissue engineering. We have fabricated a hybrid scaffold by integrating physicochemical characteristics of poly(epsilon-caprolactone) (PCL) and biomimetic property of a composite of fibrin, fibronectin, gelatin, growth factors, and proteoglycans to improve EC growth on the scaffold. Solvent cast porous films of poly(epsilon-caprolactone) was prepared using PEG as a porogen. Porosity varied between 5 and 200 microm, and FTIR spectroscopy confirmed structural aspects of PCL. Films kept in PBS for 60 days showed tensile strength and elongation matching native blood vessel. Slow degradation of the scaffold was demonstrated by gravimetric analysis and molecular weight determination. Human umbilical vein endothelial cell (HUVEC) adhesion and proliferation on bare films were minimal. FTIR spectroscopy and environmental scanning electron microscopy (ESEM) of PCL-fibrin hybrid scaffold confirmed the presence of fibrin composite on PCL film. HUVEC was subsequently cultured on hybrid scaffold, and continuous EC lining was observed in 15 and 30 days of culture using ESEM. Results suggest that the new hybrid scaffold can be a suitable candidate for cardiovascular tissue engineering.

[1]  Chrysanthi Williams,et al.  Small-diameter artificial arteries engineered in vitro. , 2005, Circulation research.

[2]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[3]  C. M. Agrawal,et al.  Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. , 2001, Journal of biomedical materials research.

[4]  J. West,et al.  Endothelialization of microporous YIGSR/PEG-modified polyurethaneurea. , 2005, Tissue engineering.

[5]  Chirathodi Vayalappil Muraleedharan,et al.  Bio-mimetic composite matrix that promotes endothelial cell growth for modification of biomaterial surface. , 2007, Journal of biomedical materials research. Part A.

[6]  Makoto Kodama,et al.  Pore size, tissue ingrowth, and endothelialization of small-diameter microporous polyurethane vascular prostheses. , 2004, Biomaterials.

[7]  Mingyan Yang,et al.  Enhancing growth human endothelial cells on Arg-Gly-Asp (RGD) embedded poly (epsilon-caprolactone) (PCL) surface with nanometer scale of surface disturbance. , 2005, Journal of biomedical materials research. Part A.

[8]  L. Krishnan,et al.  Growth factors upregulate deposition and remodeling of ECM by endothelial cells cultured for tissue-engineering applications. , 2007, Biomolecular engineering.

[9]  Lissy K Krishnan,et al.  Vascular tissue generation in response to signaling molecules integrated with a novel poly(ε‐caprolactone)–fibrin hybrid scaffold , 2007, Journal of tissue engineering and regenerative medicine.

[10]  S. Ramakrishna,et al.  Fabrication of modified and functionalized polycaprolactone nanofibre scaffolds for vascular tissue engineering , 2005, Nanotechnology.

[11]  R. Adhikari,et al.  Biodegradable synthetic polymers for tissue engineering. , 2003, European cells & materials.

[12]  Stephen F Badylak,et al.  The basement membrane component of biologic scaffolds derived from extracellular matrix. , 2006, Tissue engineering.

[13]  D. Williams,et al.  Surface properties and biocompatibility of solvent-cast poly[-caprolactone] films. , 2004, Biomaterials.

[14]  Elazer R Edelman,et al.  Effect of pre‐adsorbed proteins on attachment, proliferation, and function of endothelial cells , 2002, Journal of cellular physiology.

[15]  K. R. Resmi,et al.  Protease action and generation of beta-thromboglobulin-like protein followed by platelet activation. , 2002, Thrombosis research.

[16]  J. Schwarzbauer,et al.  Changes in cell spreading and cytoskeletal organization are induced by adhesion to a fibronectin-fibrin matrix. , 1996, Blood.

[17]  T. Maciag,et al.  An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Shalaby,et al.  Absorbable and Biodegradable Polymers , 2003 .

[19]  Haiyan Xu,et al.  Characterizing the modification of surface proteins with poly(ethylene glycol) to interrupt platelet adhesion. , 2006, Biomaterials.

[20]  E. Jaffe,et al.  Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. , 1973, The Journal of clinical investigation.

[21]  Elazer R Edelman,et al.  Tissue Engineering Therapy for Cardiovascular Disease , 2003, Circulation research.

[22]  A. Shafferman,et al.  Effect of chemical modification of recombinant human acetylcholinesterase by polyethylene glycol on its circulatory longevity. , 2001, The Biochemical journal.

[23]  L. Krishnan,et al.  A stable matrix for generation of tissue-engineered nonthrombogenic vascular grafts. , 2002, Tissue engineering.

[24]  Amy L Lerner,et al.  Fibronectin matrix polymerization increases tensile strength of model tissue. , 2004, American journal of physiology. Heart and circulatory physiology.