Prediction of extracellular matrix stiffness in engineered heart valve tissues based on nonwoven scaffolds
Tóm tắt
The in vitro development of tissue engineered heart valves (TEHV) exhibiting appropriate structural and mechanical characteristics remains a significant challenge. An important step yet to be addressed is establishing the relationship between scaffold and extracellular matrix (ECM) mechanical properties. In the present study, a composite beam model accounting for nonwoven scaffold–ECM coupling and the transmural collagen concentration distribution was developed, and utilized to retrospectively estimate the ECM effective stiffness in TEHV specimens incubated under static and cyclic flexure conditions (Engelmayr Jr et~al. in Biomaterials 26(2):175–87 2005). The ECM effective stiffness was expressed as the product of the local collagen concentration and the collagen specific stiffness (i.e., stiffness/concentration), and was related to the overall TEHV effective stiffness via an empirically determined scaffold–ECM coupling parameter and measured transmural collagen concentration distributions. The scaffold–ECM coupling parameter was determined by flexural mechanical testing of polyacrylamide gels (i.e., ECM analogs) of variable stiffness and associated scaffold-polyacrylamide gel composites (i.e., engineered tissue analogs). The transmural collagen concentration distributions were quantified from fluorescence micrographs of picro-sirius red stained TEHV sections. As suggested by a previous structural model of the nonwoven scaffold (Engelmayr Jr and Sacks in J Biomech Eng 128(4):610–22, 2006), nonwoven scaffold–ECM composites did not follow a traditional rule of mixtures. The present study provided further evidence that the primary mode of reinforcement in nonwoven scaffold–ECM composites is an increase in the number fiber–fiber bonds with a concomitant increase in the effective stiffness of the spring-like fiber segments. Simulations of potential ECM deposition scenarios using the current model indicated that the present approach is sensitive to the specific time course of tissue deposition, and is thus very suitable for studies of ECM formation in engineered heart valve tissues.
Tài liệu tham khảo
Brotchie D, Birch M, Roberts N, Howard CV, Smith VA, Grierson I (1999) Localisation of connective tissue and inhibition of autofluorescence in the human optic nerve and nerve head using a modified picrosirius red technique and confocal microscopy. J Neurosci Methods 87(1):77–5
Dolber PC, Spach MS (1987) Picrosirius red staining of cardiac muscle following phosphomolybdic acid treatment. Stain Technol 62(1):23–6
Dolber PC, Spach MS (1993) Conventional and confocal fluorescence microscopy of collagen fibers in the heart. J Histochem Cytochem 41(3):465–69
Engelmayr GC Jr, Sacks MS (2006) A structural model for the flexural mechanics of nonwoven tissue engineering scaffolds. J Biomech Eng 128(4):610–22
Engelmayr GC Jr, Hildebrand DK, Sutherland FW, Mayer JE Jr, Sacks MS (2003) A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials. Biomaterials 24(14):2523–532
Engelmayr GC Jr, Rabkin E, Sutherland FW, Schoen FJ, Mayer JE Jr, Sacks MS (2005) The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials 26(2):175–87
Engelmayr GC Jr, Papworth GD, Watkins SC, Mayer JE Jr, Sacks MS (2006a) Guidance of engineered tissue collagen orientation by large-scale scaffold microstructures. J Biomech 39(10):1819–831
Engelmayr GC Jr, Sales VL, Mayer JE Jr, Sacks MS (2006b) Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues. Biomaterials 27(36):6083–095
Engler AJ, Griffin MA, Sen S, Bonnemann CG, Sweeney HL, Discher DE (2004) Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments. J Cell Biol 166(6):877–87
Frisch-Fay R (1962) Flexible bars. Butterworths, Washington, DC, p 220
Gibson RF (1994) Principles of composite material mechanics. In: McGraw-Hill series in mechanical engineering vol xvii. McGraw-Hill, New York, p 425
Gloeckner DC, Billiar KL, Sacks MS (1999) Effects of mechanical fatigue on the bending properties of the porcine bioprosthetic heart valve. Asaio J 45(1):59–3
Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, Moran AM, Guleserian KJ, Sperling JS, Kaushal S, Vacanti JP, Schoen FJ, Mayer JE Jr (2000) Functional living trileaflet heart valves grown In vitro. Circulation. 102(19 Suppl 3): III44–III49
Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39(12):1890–900
Iyengar AKS, Sugimoto H, Smith DB, Sacks MS (2001) Dynamic in vitro quantification of bioprosthetic heart valve leaflet motion using structured light projection. Ann Biomed Eng 29(11):963–73
Junqueira LC, Bignolas G, Brentani RR (1979) Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 11(4):447–55
Junquiera LC, Junqueira LC, Brentani RR (1979) A simple and sensitive method for the quantitative estimation of collagen. Anal Biochem 94(1):96–9
Kim BS, Mooney DJ (2000) Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions. J Biomech Eng 122(3):210–15
Martin I, Obradovic B, Freed LE, Vunjak-Novakovic G (1999) Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage. Ann Biomed Eng 27(5):656–62
Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Munson ML (2005) Births: final data for 2003. Natl Vital Stat Rep 54(2):1–16
Merryman WD, Huang H-YS, Schoen FJ, Sacks MS (2006) The effects of cellular contraction on aortic valve leaflet flexural stiffness. J Biomech 39(1):88–6
Mirnajafi A, Raymer J, Scott MJ, Sacks MS (2005) The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials. Biomaterials 26(7):795–04
Mol A, Bouten CV, Zund G, Gunter CI, Visjager JF, Turina MI, Baaijens FP, Hoerstrup SP (2003) The relevance of large strains in functional tissue engineering of heart valves. Thorac Cardiovasc Surg 51(2):78–3
Niskanen K (1998) Paper physics. Book 16 of papermaking science and technology Helsinki. Published in cooperation with the Finnish Paper Engineers’ Association and TAPPIm, Atlanta 324
Perron J, Moran AM, Gauvreau K, del Nido PJ, Mayer JE Jr, Jonas RA (1999) Valved homograft conduit repair of the right heart in early infancy. Ann Thorac Surg 68(2):542–48
Peyton SR, Putnam AJ (2005) Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion. J Cell Physiol 204(1):198–09
Peyton SR, Raub CB, Keschrumrus VP, Putnam AJ (2006) The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials 27(28):4881–893
Puchtler H, Sweat F, Gropp S (1967) An investigation into the relation between structure and fluorescence of azo dyes. J R Microsc Soc 87(3):309–28
Puchtler H, Waldrop FS, Valentine LS (1973) Fluorescence microscopic distinction between elastin and collagen. Histochemie 35(1):17–0
Rabkin E, Hoerstrup SP, Aikawa M, Mayer JE Jr, Schoen FJ (2002) Evolution of cell phenotype and extracellular matrix in tissue-engineered heart valves during in-vitro maturation and in-vivo remodeling. J Heart Valve Dis 11(3):308–314(discussion 314)
Rabkin E, Schoen FJ (2002) Cardiovascular tissue engineering. Cardiovasc Pathol 11(6):305–7
Rodgers JC, Puchtler H, Gropp S (1967) Transition from elastin to collagen in internal elastic membranes. Staining, polarization, and fluorescence microscopic studies of the renal arterial system. Arch Pathol 83(6):557–66
Schwint OA, Labraga M, Cervino CO, Haffar M, Sequeiros PH, Marcos HJ (2004) A modification of the staining technique of reticular fibres for image analysis of the cardiac collagen network. Cardiovasc Pathol 13(4):213–20
Sutherland FW, Perry TE, Yu Y, Sherwood MC, Rabkin E, Masuda Y, Garcia GA, McLellan DL, Engelmayr GC Jr, Sacks MS, Schoen FJ, Mayer JE Jr (2005) From stem cells to viable autologous semilunar heart valve. Circulation 111(21):2783–791
Timoshenko S, Gere J (1972) Mechanics of materials. D. Van Nostrand, New York p 552
Whittaker P, Kloner RA, Boughner DR, Pickering JG (1994) Quantitative assessment of myocardial collagen with picrosirius red staining and circularly polarized light. Basic Res Cardiol 89(5):397–10
Willits RK, Skornia SL (2004) Effect of collagen gel stiffness on neurite extension. J Biomater Sci Polym Ed 15(12):1521–531