UMDNJ - ROBERT WOOD JOHNSON MEDICAL SCHOOL
DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE

Administrative:

Department: Pathology and Laboratory Medicine

Lab Url:

Phone Number: 732-235-4027

Fax Number: (732) 235-4825

My laboratory has been involved in applying physical techniques to the analysis of biological tissues. We are interested in analyzing how forces experienced by extracellular matrices lead to changes in the composition and organization of tissues. It is clear that mechanochemical transduction occurs in tissues as a result of the effect of forces due to gravity, locomotion and pulsatile blood flow. Key to understanding mechanochemical transduction at the cellular level is the analysis of how forces are borne by the matrix. The ability of forces to be borne by extracellular matrix arises from the ability of this tissue to store elastic energy. The ability of tissue to store elastic energy in turn is a consequence of collagen self-assembly.

Collagen Self-Assembly

Collagen molecules can spontaneously self-assemble into quarter-staggered fibrils that laterally fuse into fibril bundles and fibers. Once collagen fibers are crosslinked they are able to store elastic energy, which is key to normal tissue function. Elastic energy storage is not only important to maintaining tissue shape, but it is also important to providing resistance to mechanical trauma, and transmitting, distributing and dissipating forces in the musculoskeleton, external and internal tissues. Although there has been much research into the different collagen types that make up these tissues, little information exists concerning the role of different types of fiber forming collagens in elastic energy storage.

Results of studies conducted in my lab suggest that the triple helical portions of fibril forming collagens (types I, II and III) are made up of alternating rigid and flexible domains. These domains alternate on average about every 10 to 11 amino acid residues and the flexibility of these domains in types II and III collagen molecules appears to be higher than that found in type I collagen. The flexible domains are conserved in the quarter-staggered fibril and codistribute with the 12 positive staining bands that characterize the positive staining pattern seen within the D period. In vitro, we have shown that type I collagen fibrils are made up of 4 nm wide microfibrils that laterally fuse during self assembly. The microfibril appears to be the mechanical unit that stores elastic energy during tensile loading.

Molecular Basis of Elastic Energy Storage in Extracellular Matrix.

The ability of extracellular matrix to store elastic energy during tensile loading allows force transmission in tendons as well as for energy dissipation in cartilage. The molecular mechanism for energy storage involves stretching of the flexible domains in the collagen molecule that are crosslinked into a continuous filament within the microfibril. Elastic energy storage appears to involve pairs of charged residues since lowering or raising the pH decreases the ability to store energy elastically.

Viscous Dissipation of Energy in Extracellular Matrix

Although one of the primary functions of extracellular matrices is to store elastic energy, this energy has to be either transmitted or dissipated to prevent cellular and tissue damage. We have examined the mechanism for energy dissipation in skin, tendon, cardiovascular tissue and cartilage. The primary mechanism for energy dissipation in extracellular matrix involves viscous fibrillar slippage. During fibrillar slippage collagen fibrils slide by neighboring fibrils dissipating energy through viscous processes.

Physiologic Role of Elastic Energy Storage in Extracellular Matrices

Energy storage in extracellular matrices has several physiologic roles. In the musculoskeletal system, the muscle does work on the tendon and stores elastic energy by deforming the flexible regions of the collagen molecule. This energy is reversibly returned by putting tension on bone at the attachment site. In this manner elastic energy stored in collagen fibrils in tendon, which are composed primarily of type I collagen, is then transmitted to the bone during locomotion. In contrast, in cartilage the primary function is to act as a shock absorber by dissipating elastic stored energy. During locomotion, energy transmitted to bones is used for movement of the bones that are connected through the articular cartilage in the joint. As weight is applied to the joint, the cartilage stores the energy elastically and then distributes it across the joint surface without causing cartilage tearing. In osteoarthritis the energy storage capabilities of articular cartilage are drastically reduced resulting in stress concentration and damage to the cartilage surface.

Vascular Stent Program

In collaboration with the Department of Radiology, we have developed the theoretical basis to design self-expanding z-stents that can be used to apply a defined radial force to vessel walls. The radial force exerted by the stent can be increased and the effects of radial force on intimal hyperplasia can be studied. Preliminary results suggest that low radial forces do not appear to stimulate intimal hyperplasia. We are begining to study how high the radial force can be increased before intimal hyperplasia results in vessel stenosis.
 

1. Yannas, I.V. and Silver, F.  Thromboresistant Analogs of Vascular Tissue.  Polymer Preprints 16, 529, 1975.

2. Silver, F.H., Yannas, I.V. and Salzman, E.W.  Glycosaminoglycan Inhibition of Collagen Induced Platelet Aggregation. Thrombosis Research 13, 267, 1978.

3. Silver, F.H., Yannas, I.V. and Salzman, E.W.  In Vitro Blood Compatibility of Glycosaminoglycan Precipitated Collagens. Journal of Biomedical Materials Research 13, 701, 1979.

4. Silver, F.H., Langley, K.H. and Trelstad, R.L.  Type I Collagen Fibrillogenesis: Initiation Via Reversible Linear and Lateral Growth Steps.  Biopolymers 18, 2523, 1979.

5. Silver, F.H. and Trelstad, R.L.  Linear Aggregation and the Turbidimetric Lag Phase: Type I Collagen Fibrillogenesis in Vitro. Journal of Theoretical Biology 81, 515, 1979.

6. Silver, F.H. and Trelstad, R.L. Type I Collagen Structure in Solution and Properties of Fibril Fragments. Journal of Biological Chemistry 255, 9427, 1980.

7. Trelstad, R.L., Lawley, K. R., Hayashi, K., Ehrlich, H.P. and Silver, F.H.  Type V collagen from the Chick Embryo:  Biochemical, Physiochemical and Ultrastructural Characteristics. Collagen and Related Research 1, 39, 1981.

8. Silver, F.H. and Trelstad, R.L. Physical Properties of Type I Collagen in Solution: Structure of α chains, ß and γ -components and Two Component Mixtures.  Biopolymers 20, 359, 1981.

9. Silver, F.H.  Type I Collagen Fibrillogenesis in Vitro: Additional Evidence for the Assembly Mechanism.  Journal of Biological Chemistry 256, 4973, 1981.

10. Swann, D.A., Slayer, H.S., and Silver, F.H.  The Molecular Structure of LGP-I, the Boundary Lubricant for Articular Cartilage. Journal of Biological Chemistry 256, 5921, 1981.

11. Silver, F.H.  A Molecular Model for Linear and Lateral Growth of Type I Collagen Fibrils. Collagen and Related Research 2, 219, 1982.

12. Bender, E., Silver, F.H., Hayashi, K. and Trelstad, R.L. Type I Collagen SLS Banding Patterns:  Evidence that the α -2 chain is in the A position. Journal of Biological Chemistry 257, 9653, 1982.

13. Swann, D.A., Silver, F.H., Sotman, S.L. and Hermann, H. Measurements of Reducing End Groups on Bovine Vitreous Humour Hyaluronic Acid by Reaction with 14 [c] Cyanide. Biochemical Journal 207, 409, 1982.

14. Silver, F.H. and Swann, D.A.  Laser Light Scattering Measurements on Vitreous and Rooster Comb Hyaluronic Acids. International Journal of Biological Macromolecules 4, 425, 1982.

15. Silver, F.H.  A Two Step Model For Lateral Growth of Collagen Fibrils.  Collagen and Related Research 3, 167, 1983.

16. Birk, D.E. and Silver, F.H.  Corneal and Scleral Type I Collagens: Analyses of Physical Properties And Molecular Flexibility. International Journal of Biological Macromolecules 5, 209, 1983.

17. Bender, E. , Silver, F.H. and Hayashi, K. Models of Carboxyl Telopeptide Conformations Based on Type I Collagen Fibril Banding Patterns. Collagen and Related Research 3, 407, 1983.

18. Dunn, M.D. and Silver, F.H.  Viscoelastic Behavior of Human Connective Tissues:  Relative Contribution of Viscous and Elastic Components. Connective Tissue Research 12, 59, 1983.

19. Silver, F.H. and Birk, D.E.  Kinetic Analysis of Type I Collagen Fibrillogenesis: Use of Turbidity-Time Data. Collagen and Related Research 3, 393, 1983.

20. Birk, D.E. and Silver, F.H.  Kinetic Analysis of Collagen Fibrillogenesis: II.  Corneal and Scleral Type I Collagen. Collagen and Related Research 4, 265, 1984.

21. Birk, D.E. and Silver, F.H.  Collagen Fibrillogenesis In Vitro: Comparison of Types I, II and III. Archives Biochemistry and Biophysics 235, 178, 1984.

22. Silver, F.H. and Birk, D.E.  Molecular Structure of Collagen In Solution:  Comparison of Types I, II, III and V. International Journal of Biological Macromolecules 6, 125, 1984.

23. Swann, D.A., Silver, F.H. and Larsson, A.  On The Structure of Bovine Articular Cartilage High Density Proteoglycans. Isolation of the Keratin Sulfate and Chondroitin Sulfate Side Chains. Journal of Biological Chemistry 259, 7693, 1984.

24. Doillon, C., Whyne, C.F., Berg, R.A., Olson, R.M. and Silver, F.H. Fibroblast-Collagen Sponge Interactions and the Spatial Deposition of Newly Synthesized Collagen Fibers In Vitro and In Vivo. Scanning Electron Microscopy III, 1313, 1984.

25. Weadock, K., Olson, R.M. and Silver, F.H.  Evaluation of Collagen Crosslinking Techniques.   Biomaterials, Medical Devices and Artificial Organs 11, 293, 1984.

26. Swann, D.A., Silver, F.H., Sotman, S.L. and Hermann, H.  Isolation and Properties of Proteoglycans from Bovine and Human Synovial Fluids. Journal of Biological Chemistry 259, 7693, 1984.

27. Dunn, M.G., Silver, F.H. and Swann, D.A.  Mechanical Analysis of Hypertrophic Scar Tissue:  Structural Basis of Apparent Increased Rigidity. Journal of Investigative Dermatology 84, 9, 1985.

28. Swann, D.A., Silver, F.H., Slayter, H.S. and Shore, E.  The Molecular Structure and Lubricating Activity of Lubricin Isolated From Bovine Ankle and Knee and Human Knee Synovial Fluids. Biochemical Journal 225, 1951, 1985.

29. Bender, E. and Silver, F.H.  Type I Collagen Segment Long Spacing Banding Patterns: Improved Correlation with Models Using a Variable h Spacing.  Biopolymers 24, 2195, 1985.

30. Brokaw, J., Doillon, C.J., Hahn, R.A., Birk, D.E., Berg, R.A. and Silver, F.H.  Turbidimetric and Morphological Studies of Type I Collagen Fiber Self Assembly In Vitro and the Influence of Fibronectin. International Journal of Biological Macromolecules 7, 135, 1985.

31. McBride, D.J., Hahn, R.A. and Silver, F.H.  The Morphological Characterization of Tendon Development During Chick Embryogenesis: Measurements of Birefringence Retardation. International Journal of Biological Macromolecules 7, 71, 1985.

32. Doillon, C.J., Dunn, M.G., Berg, R.A. and Silver, F.H.  Collagen Deposition During Wound Repair. Scanning Electron Microscopy II, 897, 1985.

33. Doillon, C.J., Dunn, M.G., Bender, E. and Silver, F.H.  Collagen Fiber Formation In Vivo:  Development of Wound Strength and Toughness. Collagen and Related Research 5, 481, 1985.

34. Doillon, C.J. and Silver, F.H.  Collagen-Based Wound Dressing: Effects of Hyaluronic Acid and Fibronectin on Wound Healing. Biomaterials 7, 3, 1986.

35. Farber, S., Garg, A., Birk, D.E. and Silver, F.H.  Collagen Fibrillogenesis In Vitro:  Evidence For Pre-Nucleation and Nucleation Steps. International Journal of Biological Macromolecules 8, 37, 1986.

36. Berg, R.A., Birk, D.E. and Silver, F.H.  Physical Characterization of Procollagen Secreted By Chick Tendon Fibroblasts. International Journal of Biological Macromolecules 8, 177, 1986.

37. Weadock, K., Silver, F.H. and Wolff, D. Diffusivity of I125-Calmodulin Through Collagen Membranes: Effect of Source Concentration and Membrane Swelling Ratio. Biomaterials 7, 263, 1986.

38. Doillon, C.J., Whyne, C.F., Brandwein, S. and Silver, F.H. Collagen-Based Wound Dressings: Control of Pore Structure and Morphology. Journal of Biomedical Materials Research 20, 1219, 1986.

39. Kalath, S., Tsipouras, P. and Silver, F.H. Non-invasive Assessment of Aortic Mechanical Properties. Annals of Biomedical Engineering 14, 513, 1986.

40. Birk, D.E. and Silver, F.H.  Molecular Structure and Physical Properties of Type IV Collagen in Solution. International Journal of Biological Macromolecules 9, 7, 1987.

41. Kalath, S., Tsipouras, P. and Silver, F.H. Increased Aortic Root Stiffness Associated with Osteogenesis Imperfecta. Annals of Biomedical Engineering 15, 91, 1987.

42. Doillon, C.J., Silver, F.H. and Berg, R.A.  Fibroblast Growth On a Porous Collagen Sponge.  Biomaterials 8, 195, 1987.

43. Weadock, K.S., Wolff, D. and Silver, F.H.  Diffusivity of I125 Labeled Macromolecules Through Collagen: Mechanism of Diffusion and Effect of Adsorption.  Biomaterials 8, 105, 1987.

44. Doillon, C.J., Wasserman, A.J., Berg, R.A. and Silver, F.H. Behavior of Fibroblasts and Epidermal Cells Cultivated on Analogues of Extracellular Matrix. Biomaterials 9, 9, 1988.

45. Doillon, C.J., Silver, F.H., Olson, R.M., Kamath, C.Y. and Berg, R.A. Fibroblast and Epidermal Cell Type I Collagen Interactions: Cell Culture and Human Studies.  Scanning Electron Microscopy 2, 985, 1988.

46. McBride, D.J., Trelstad, R.L. and Silver, F.H.  Structural and Mechanical Assessment of Developing Chick Tendon. International Journal of Biological Macromolecules 10, 194, 1988.

47. Dunn, M.G., Doillon, C.J., Berg, R.A., Olson, R.M. and Silver, F.H. Wound Healing Using A Collagen Matrix: Effect of DC Electrical Stimulation. Journal of Biomedical Materials Research 22, 191, 1988.

48. Glasgold, M.J., Kato, Y.P., Christiansen, D., Hauge, J.A., Glasgold, A.I. and Silver, F.H. Mechanical Properties of Septal Cartilage Homografts. Otolaryngology-Head and Neck Surgery 99,374, 1988.

49. Jain, M.K., Chernomorsky, A., Silver, F.H. and Berg, R.A. Material Properties of Living Soft Tissue Composites. Journal of Biomedical Materials Research 22, 311, 1988.

50. Doillon, C.J., Dunn, M.G. and Silver, F.H. Relationship Between Mechanical Properties and Collagen Structure of Closed and Open Wounds. Journal Biomechanical Engineering 110, 371, 1988.

51. Wasserman, A.J., Doillon, C.J., Glasgold, A.I., Kato, Y.P., Christiansen, D., Rizvi, A., Wong, E., Goldstein, J. and Silver, F.H. Clinical Application of Electron Microscopy in The Analysis of Collagenous Biomaterials. Scanning Microscopy International 2, 1635, 1988.

52. Glasgold, A.I., Glasgold, M.J. and Silver, F.H.  Cartilage, The Preferred Grafting Material in Nasal Surgery. American Journal of Rhinology 3, 167, 1989.

53. Silver, F.H., Doillon, C.J., Rojo, B., Olson, R.M., Kamath, C.Y.and Berg, R.A.  Collagenous Materials Enhance Healing of Chronic Skin Ulcers. Biomedical Materials and Devices. Materials Research Society 110, 371, 1989.

54. Kato, Y.P., Christiansen, D.L., Hahn, R.A., Shieh, S-J., Goldstein, J. and Silver, F.H. Mechanical Properties of Collagen Fibers: A Comparison of Reconstituted and Rat Tail Tendon Fibers. Biomaterials 10, 38, 1989.

55. Law, J.K., Parsons, J.R., Silver, F.H. and Weiss, A.B. An Evaluation of Purified Reconstituted Type I Collagen Fibers. Journal Biomedical Materials Research. Applied Biomaterials 23, 961, 1989.

56. Garg, A.K., Berg, R.A., Garg, H.G. and Silver, F.H.  Effect of Proteoglycans On Type I Collagen Fiber Formation. Biomaterials 10, 413, 1989.

57. Goldstein, J.D., Tria, A.J., Zawadsky, J.P., Kato, Y.P., Christiansen, D. and Silver, F.H. Development of a Reconstituted Collagen Tendon Prosthesis. Journal Bone and Joint Surgery 71A, 1183, 1989.

58. Wasserman, A.J., Kato, Y.P., Christiansen, D., Dunn, M.G. and Silver, F.H.  Achilles Tendon Replacement By a Collagen Fiber Prosthesis: Morphological Evaluation of Neotendon Formation. Scan.  Micro. Intl., 3, 1183, 1989.

59. Doillon, C.J., Altchek, A. and Silver, F.H.  Method For Growth of Vaginal Mucosal Cells on A Collagen Sponge Matrix. Results of Preliminary Studies. Journal of Reproductive Medicine 35, 203, 1990.

60. Meade, K.R. and Silver, F.H.  Immunogenicity of Collagenous Implants.  Biomaterials 1, 176, 1990.

61. Kato, Y.P. and Silver, F.H.  Formation of Continuous Collagen Fibers: Evaluation of Biocompatibility and Mechanical Properties. Biomaterials 11, 169, 1990.

62. Wong, E., Christiansen, D., Rizvi, A., Geller, H. and Silver, F.H. A Method For Preparation of Etched Collagen Fibers That Support Neurite Outgrowth. J. Applied Biomaterials 1,225,1990.

63. Buntin, C.M. and Silver, F.H.  Non-Invasive Assessment of Mechanical Properties of Peripheral Arteries. Annals Biomedical Engineering 18, 549, 1990.

64. Collins, R.L.L., Christiansen, D., Zazanis, G.A. and Silver, F.H. Use of Collagen Film as a Dural Substitute. J. Biomed. Mat. Res. 25, 267, 1991.

65. Marks, M.G., Doillon, C.J. and Silver, F.H.  Effects of Fibroblasts and Fibroblast Growth Factor on Facilitation of Dermal Wound Healing By Type I Collagen Matrices. J. Biomed. Mat. Res. 25, 663, 1991.

66. Kato, Y.P., Dunn, M.G., Zawadsky, J.P., Tria, A.J. and Silver, F.H. Regeneration of Achilles Tendon Using a Collagen Tendon Prosthesis: Results of a Year Long Implantation study. Journal Bone and Joint Surgery 73-A, 561, 1991.

67. Wasserman, A.J., Kato, Y.P. and Silver, F.H.  A Simple Method For Ultrastructural Evaluation of Fragile Collagenous Biomaterials. Cells and Materials 1, 41, 1991.

68. Glasgold, A.I., Glasgold, M.J. and Silver, F.H.  The Use of Collagen Matrix To Enhance Closure of Facial Defects. Ear, Nose and Throat Journal 70, 531, 1991.

69. Rizvi, A.H., Wasserman, A.J., Zazanis, G.A. and Silver, F.H. Evaluation of a Peripheral Nerve Prosthesis Composed of Longitudinally Aligned Collagen Fibers. Cells and Materials 1, 279, 1991.

70. Dunn, M.G., Tria, A.J., Kato, Y.P., Bechler, J.R., Ochner, R.S., Zawadsky, J.P. and Silver, F.H. Anterior cruciate ligament replacement using a composite collagenous prosthesis: A biomechanical and histological study in rabbits.  American Journal of Sports Medicine 20, 507, 1992.

71. Silver, F.H., Marks, M., Kato, Y.P., Li, C., Pulapura, S,. and Kohn, J.  Tissue compatibility of tyrosine derived polycarbonates and polyiminocarbonates: An initial evaluation. J. Long-Term Effects of Medical Implants 1, 329, 1992.

72. Christiansen, D. and Silver, F.H., Biomimetic Mineralization of an Aligned, Self-Assembled Collagenous Matrix, Materials Research Society Symposium Proceedings  255, 367, 1992.

73. Christiansen, D., Pins, G., Wang, M.C., Dunn, M.G. and Silver, F.H., Collagenous Biocomposites For The Repair of Soft Tissue Injury, Tissue-Inducing Biomaterials, Materials Research Society Symposium Proceedings  252, 151,1992.

74. Christiansen D, and Silver, F.H., The pH dependent mineralization of a reconstituted collagen fiber:  Physical and ultrastructural characterization. Biomimetics 1, 265, 1992.

75. Silver, F.H., Kato, Y.P., Ohno, M. and Wasserman, A.J., Analysis of mammalian connective tissue: Relationship between hierarchical structures and mechanical properties. J. Long-Term Effects of Medical Implants 2, 165, 1992.

76. Christiansen, D.L., Pins, G. and Silver, F.H., A simply freeze fracture technique for scanning electron microscopy of collagenous biomaterials. Cells and Materials  3, 189, 1993.

77. Silver, F.H. and Glasgold, A.J., Silicone Facial Implants: Are they safe?  J. Long-Term Effects of Medical Implants 3, 313, 1993.

78. Christiansen, D. and Silver, F.H., Mineralization of an axially aligned collagenous matrix:  A morphological and ultrastructural study. Cells and Materials  3, 177, 1993.

79. Rizvi, A.H., Pins, G. and Silver, F.H., Peripheral nerve regeneration in the presence of collagen fibers: effect of removal of the distal nerve stump. Clinical Materials 16, 73, 1994.

80. Wang, M.-C, Pins, G.D., and Silver, F.H., Collagen Fibers with improved strength for the repair of soft tissue injuries. Biomaterials 15, 507, 1994.

81. Silver, F.H., LiBrizzi, J., Pins, G. and Wang, M-C., Physical properties of hyaluronic acid and hydroxypropylomethycellulose in solution: evaluation of coating and lubricating activity.  Journal of Applied Biomaterials 5, 89, 1994.

82. Silver, F.H., LiBrizzi, J.J. and Benedetto, D., Physical properties of model viscoelastic materials. J. Applied Biomaterials 5, 227, 1994.

83. Silver, F.H. And Mass, C.S., Biology of synthetic facial implant materials. Facial Plastic Surgery Clinics of North America 2, 241, 1994.

84. Silver, F.H., Pins, G.D., Rizvi, A., Olson, R.M. and D’Aguillo, A., Silicone gel-filled breast implants: Is local inflammation associated with fat necrosis?  The Breast Journal 1,17,1995.

85. Landis, W.J., LiBrizzi, J.J., Dunn, M.G. and Silver, F.H., A study of the relationship between mineral content and mechanical properties of turkey gastrocnemius tendon. Journal of Bone and Mineral Research 10, 859, 1995.

86. Silver, F.H., Wang M.-C. and Pins, G.D., Preparation and use of fibrin glue in surgery:  A review.  Biomaterials 16. 891, 1995.

87. Silver, F.H. And Glasgold, A.L., Performance Standards for medical device approvals. Arch. Otolaryngol. Head Neck Surgery 21, 719, 1995.

88. Silver, F.H., Wang, M.-C. and Pins, G.D., Preparation of fibrin glue: A study of chemical and physical methods.  J. Applied Biomaterials 6, 175, 1995.

89. Pins, G.D. and Silver, F.H., A self-assembled collagen scaffold suitable for use in soft and hard tissue replacement. Materials Science & Engineering, Biomimetic Materials, Sensors and Systems C, 101, 1995.

90. Wang, M.C., Pins, G.D. and Silver, F.H., Preparation of fibrin glue: The effects of calcium chloride and sodium chloride. Materials Science and Engineering, Biomimetic Materials, Sensors and Systems C3, 131-135, 1995.

91. Pins, G.D., Huang, E.K., Christiansen, D.L. and Silver, F.H., Effects of axial strain on the tensile properties and failure mechanism of self-assembled collagen fibers. J. Applied Polymer Science 63, 1429, 1997.

92. Pins, G.D., Christiansen, D.L., Patel, R. and Silver, F.H., Self-assembly of collagen fibers.  Influence of fibrillar alignment and decorin on mechanical properties. Biophysical J. 73, 2164, 1997.

93. Snowhill, P.B., Olson, R.M. and Silver, F.H., Implants and fat tissue necrosis. The Breast Journal 6, 1, 2000.

94. Silver, F.H. Christiansen, D.L., Snowhill, P., Chen, Y. and Landis, W.J., Role of mineral in the storage of elastic energy in turkey tendons. Biomacromolecules 1, 180, 2000.

95. Silver, F.H., Christiansen, D.L., Snowhill, P. And Chen, Y., Role of storage on changes in the mechanical properties of tendon and self-assembled collagen fibers.  Connective Tissue Research 41, 155, 2000.

96. Christiansen, D.L., Huang, E.K. and Silver, F.H., Assembly of type I collagen: fusions of fibril subunits and the influence of fibril diameter on mechanical properties. Matrix Biology 19, 409, 2000.

97. Silver, F.H., Christiansen, D.L., Snowhill, P.B. And Chen, Y., Transition from viscous to elastic-based dependency of mechanical properties of self-assembled type I collagen fibers. Journal Applied Polymer Science 79, 134, 2001.

98. Silver, F.H., Freeman, J.W., Horvath, I. and Landis, W.J., Molecular basis for elastic energy storage in mineralized tendon. Biomacromolecules 2, 750-756, 2001.

99. Silver, F.H., Freeman, J. and DeVore, D., Viscoelastic properties of human skin and processed dermis. Skin Research and Technology 7, 18, 2001.

100. Snowhill, P.B., Nosher J.L., Segal, R.L. and Silver, F.H., Characterization of radial forces in Z-stents. Interventional Radiology 36, 521, 2001.

101. Silver, F.H., Horvath, I., and Foran, D., Viscoelasticity of the vessel wall: role of collagen and elastic fibers. Critical Reviews in Biomedical Engineering 29, 279, 2001.

102. Silver, F.H., Freeman, J., and Seehra, G.P., Collagen self-assembly and development of matrix mechanical properties. in press, J. Biomechanics.

103. Silver, F.H., Bradica, G. And Tria, A., Relationship among biomechanical, biochemical and cellular changes associated with osteoarthritis. Critical Reviews In Biomedical Engineering 29, 373-391, 2001.

104. Silver, F.H., Bradica, G. and Tria, A.., Viscoelastic behavior of osteoarthritic cartilage. Connective Tissue Research 42, 223-233, 2001.

105. Silver, F.H., Seehra, P. and Freeman, J.W. and Devore, D., Viscoelastic properties of young and old human dermis: Evidence that elastic energy storage occurs in the flexible regions of collagen and elastin. J. Applied Polymer Science 86, 1978-1985, 2002.

106. Silver, F.H., Bradica, G. and Tria, A., Elastic energy storage in human articular cartilage: estimation of the elastic spring constant for type II collagen and changes associated with osteoarthritis. Matrix Biology 21, 129-137, 2002.

107. Silver, F.H., Ebrahimi, A. and Snowhill, P.B., Viscoelastic properties of self-assembled type I collagen fibers: Molecular basis of elastic and viscous behaviors. Connective Tissue Research 43, 1-12, 2002.

108. Silver, F.H., Horvath, I. and Foran, D.J., Mechanical implications of the domain structure of fibril forming collagens: Comparison of the molecular and fibrillar flexibility of α -chains found In types I, II and III collagens. J. Theoretical Biology 216, 243-254, 2002.

109. Silver, F.H., Siperko, L.M. and Seehra, G.P., Mechanobiology of force transduction in dermis. Skin Research and Technology 8, 1-21, 2002.

110. Silver, F.H. and Bradica, G., Mechanobiology of cartilage: how do internal and external stresses affect mechanochemical transduction and elastic energy storage? Biomechanics & Modeling In Mechanobiology 1, 1-19, 2002.

111. Landis, W.J. and Silver, F.H., The structure and function of normally mineralizing tendons. Comparative Biochemistry and Physiology, Part A, 2002, in press.

112. Silver, F.H, Contribution of mechanophysiology in aging of extracellular matrix. Invited min-review J. Applied Physiology in preparation.

113. Silver, F.H. and Siperko, L.M. Role of extracellular matrix in mechanochemical transduction. Invited review for Critical Reviews in Biomedical Engineering, in preparation.

114. Silver, F.H., Snowhill, P.B. and Foran, D., Mechanical behavior of vessel wall: A comparative study of aorta, vena cava, and carotid artery, submitted for publication.

Reviews, Invited Papers, Books

1. Trelstad, R.L. and Silver, F.H.  Matrix Polymerization.  In:  The Cell Biology of the Extracellular Matrix.  E.D. Hay, ed., Academic Press, N.Y. Chapter 7, 1981.

2. Silver, F.H.  Physical Biochemistry of Collagen.  Invited paper for the 64th Conference of the Chemical Institute of Canada, Halifax, Nova Scotia, June, 1981.

3. Silver, F.H.  Collagen Fibrillogenesis.  Invited speaker for Gordon Conference on Collagen.  July 1, 1981.

4. Trelstad, R.L., Birk, D.E. and Silver, F.H.  Collagen Fibrillogenesis in Tissues, in Solution and from Modeling:  A Synthesis. Investigative Dermatology 79, 109s, 1982.

5. Trelstad, R.L., Birk, D.E. and Silver, F.H.  Cellular and Collagen Fibrillar Polarity In Developing Chick Limb Tendon.  Limb Development and Regeneration.  Alan R. Liss, Inc., N.Y., Part A,  246-249, 1983.

6. Dunn, M.G., Kalath, S., Lai, W., Tsipouras, P., Silver, F.H. and Langrana, N.  Mechanical Properties of Connective Tissues. Analysis of Genetic Disorders.  New York Academy of Sciences, 460, 426, 1986.

7. Silver, F.H.  Biological Materials:  Structure, Mechanical Properties And Modeling of Soft Tissues.  NYU Press, New York, 1987.

8. Pachence, J., Berg, R.A. and Silver, F.H.  Collagen:  Its Place in the Medical Device Industry.  Medical Device and Diagnostic Industry 9, 49, 1987.

9. Weadock, K.S., Pachence, J.M., Berg, R.A. and Silver, F.H.   Polymeric Materials Assessment of Skin Biocompatibility, In:  Transdermal Controlled Systemic Medications edited by Y.W.  Chien, Marcel Dekker, Inc., New York, Chapter 5, 1987.

10. Silver, F.H. and Doillon, C.J.  Biocompatibility:  Interactions of Biological and Implantable Materials.  VCH Publishers, New York, New York, 1989.

11. Silver, F.H. and Doillon C.J.  Skin:  Structure-Mechanical Property Relationships, invited paper for Biomechanics Symposium.  American Society of Mechanical Engineers, 1987.

12. Garg, A.K. and Silver, F.H.  Collagen Fiber Formation:  Effect of Proteoglycans.  Proc. 13th Northeast Bioengineering Conf., IEEE,  Phil. PA, 86-89,1987.

13. Garg, A.K. and Silver, F.H.  Collagen Fiber Formation:  Effect of Glycosaminoglycans.  Proc. IEEE/Eng. in Med. and Biol. Soc., Boston, 1987.

14. Shieh, S.-J., Kato, P.Y. and Silver, F.H.  Effect of Crosslinking On Mechanical Properties of Reconstituted Collagen Fibers.  Proc. IEEE/Eng. in Med. and Biol. Soc., Boston, 1987.

15. Garg, A.K., Wasserman, J., Garg, H. and Silver, F.H.  Effect of Proteoglycans On Collagen Fiber Formation.  Biomedical Sciences Instrumentation, Instrumentation Sciences of America, Research Triangle Park 24, 93, 1988.

16. Buntin, C.M. and Silver, F.H.  Noninvasive Measurement of Rabbit Aortic Wall Thickness Using Ultrasound and Histological Analysis, Biomedical Sciences Instrumentation, Instrumentation Sciences of America, Research Triangle Park, 24, 119, 1988.

17. Kato, P., Goldstein, J.D., Christiansen, D.A., Zawadsky, J.P., Tria, A.J. and Silver, F.H.  Short Term Assessment of  Reconstituted Collagen Tendon/Ligament Prosthesis.  Biomedical Sciences Instrumentation, Instrumentation Sciences of America, Research Triangle Park, 24, 87, 1988.

18. Wasserman, A.J., Christiansen, D.L., Kato, Y.P., Glasgold, A.J. and Silver, F.H.  An Electron Histochemical And Ultrastructural Evaluation of Human Nasal Septal Cartilage Grafts Stored in Merthiolate® and Alcide ®.  Proceedings 46th Annual Elect. Microscopy Soc. 244, 1988.

19. Silver, F.H., Christiansen, D.L. and Buntin, C.M.  Mechanical  Properties of Aorta: A Review, CRC Critical Reviews in Biomedical Engineering 17, 323, 1989.

20. Silver, F.H., Kato, Y.P., Christiansen, D.L. and Wasserman, A.J. Self-Assembly and Reconstitution of Tissue Analogs, Workshop on Biostructures As Composite Materials Systems. Case Western Reserve University, October 23-25, 1989.

21. Silver, F.H.  Collagen Structure and Mechanical Properties of Connective Tissue, invited paper Gordon Research Conference on Bioengineering and Orthopaedic Science, Andover, N.H., Aug. 6-10, 1990.

22. Glasgold, A.I. and Silver, F.H. (editors) Applications of Biomaterials In Facial Plastic Surgery, CRC Press, Boca Raton, FL., 1991.

23. Silver, F.H. and Parsons, J.R.  Repair of skin, bone and cartilage, In:  Applications of Biomaterials in Facial Plastic Surgery, CRC Press, Boca Raton, FL., 65, 1991.

24. Christiansen, D.L., Riley, D.J., Tozzi, C.A. and Silver, F.H.  The Mechanical Properties of the Extracellular Matrix. In:  The Extracellular Matrix and the Uterus, Cervix and Fetal Membranes, edited by P.C. Leppert and F. Woessner, Perinatology Press, Ithaca, N.Y., 1991.

25. Silver, F.H., Tria, A.J., Zawadsky, J.P. and Dunn, M.G.  Anterior cruciate ligament replacement:  Structure, healing and repair.  J. Long-Term Medical Implants 1, 135, 1991.

26. Birk, D.E., Silver, F.H. and Trelstad, R.L.  Matrix Polymerization. In:  The Cell Biology of the Extracellular Matrix,  E.D. Hay, ed., Academic Press, N.Y., 2nd edition, 221, 1991.

27. Silver, F.H. and Pins, G., Cell growth on collagen:  A review of tissue engineering using scaffolds containing extracellular  matrix.  J. Long-Term Effects of Medical Implants 2, 67, 1992.

28. Silver, F.H., Kato, Y.P., Ohno, M. and Wasserman, A.J.  Analysis of mammalian connective tissues.  Relationship between hierarchical structures and mechanical properties.  J. Long-Term Effects of Medical Implants 2, 165, 1992.

29. Silver, F.H., LiBrizzi, J. and Benedetto, D., Use of viscoelastic solutions in ophthalmology:  A review of physical properties and long-term effects, J. Long-Term Effects of Medical Implants 2, 49, 1992.

30. Silver, F.H. and Wang, M-C.,  A Review of the Etiology and Treatment of Skin Ulcers with Wound Dressings:  Comparison of the  Effects of Occlusive and Nonocclusive Dressings, J. Long-Term Effects of Medical Implants 2, 267, 1992.

31. Christiansen, D.L. and Silver, F.H., Analysis of the mechanical properties of Ca/P  Nanocomposite, In:  Bioceramics, Vol. 6, edited by P. Duchyne and D. Christiansen, Butterworth-Hunemann, Ltd., Philadelphia, Pa, 495, 1993.

32. Silver, F.H. and Glasgold, A.I., Clinical studies used in medical device approvals: Can they be improved, J. Long-Term Effects of Medical Implants No 3, editorial, 1993.

33. Silver, F.H., Immunogenicity of implants:  Clinical signs and animal testing, Evaluation And Testing Of Cardiovascular Devices, Society For Biomaterials, 6518 Walker Street, Suite 215, Minneapolis, MN, pp 40-47, 1993.

34. Silver, F.H. and Olson, R.M., Silicone implants and autoimmune disease: Fact or fantasy?  Thirteenth Southern Biomedical Engineering Conference, Washington, D.C., April 16-17, 1994.

35. Silver, F.H.  Biomaterials, Medical Devices and Tissue Engineering:  An Integrated Approach, Chapman and Hall, London 1994.

36. Silver, F.H. and Maas, C.S., Biology of synthetic facial implant materials, Facial Plastic Surgery Clinics of North America 2, 241, 1994.

37. Silver, F.H. and Glasgold, A.J., Cartilage wound healing - An Overview, In:  Otolaryngologic Clinics of North America, 28,no. 5, 847, 1995.

38. Silver, F.H., Pins, G.D., Wang, M.-C. and Christiansen, D., Collagenous biomaterials as models of tissue-inducing implants, Chapter 36, In:  Encyclopedia of Biomaterials and Engineering, Marcel Dekker, Inc, vol 2, part B, 1245, 1995.

39. Silver, F.H. and Benedetto, D., Polysaccharices used in ophthalmology, In:  Polysaccharides in Medicine and Biotechnology, edited by S. Dimitriu, Marcel Dekker, Inc., vol. 24, 689,1996.

40. Silver, F.H., Relationship between hierarchical structure and mechanical properties of arteries, Proceedings of the 1st International Conference on Functional Abnormalities of the Aorta, Chapter 8, 133, 1996.

41. Silver, F.H. and Garg., A., Collagen: characterization, processing and medical applications, In: Handbook of Biodegradable Polymers, edited by A.J. Domb, J. Kost and D. M. Wiseman, Chapter 17, Hardwood Academic Publishers, Australia, 1997.

42. Silver, F.H. And Christiansen, D.L., Biomaterials Science and Biocompatibility, Springer-Verlag, New York, 1999.

43. Silver, F.H. and Christiansen, D.L., Self maintenance by healing mechanisms, In: Regeneration and The Life Span, edited by K. Sames, Ecomed Publishers, Germany, 2000.

44. Snowhill, P.B., Nosher, J.L. And Silver, F.H., The importance of radial forces in vascular stent design, In: Biomedical Engineering and Devices: Human Applications, edited by D.L. Wise et al., Marcel Dekker, Inc., Vol. 1 Chapter 9, 2000. 

45. Silver, F.H. And Christiansen, D.L., Collagen scaffolds for tissue regeneration, In: Biomedical Engineering and Devices: Human Applications, edited by D.L. Wise et al., Marcel Dekker, Inc., Vol. 1 Chapter 34, 2000. 

46. Silver, F.H., Kronengold, R.T., Wang, M-C., Benedetto, D. And Christiansen, D.L., Development of a modified fibrin adhesive: What can we learn from biological adhesive mechanisms? In: Biomedical Engineering and Devices: Human Applications, edited by D.L. Wise et al., Marcel Dekker, Inc., Vol. 1 Chapter 41, 2000. 

47. Silver, F.H., Bradica, G. and Tria, A. , Structure and biomechanics of articular cartilage, In : The Adult Knee, edited by J. Callaghan, A Rosenberg, H. Rubash, P. Simonian and T. Wickiewicz, Lippincott, Williams & Wilkins, Philadelphia, PA, chapter 8, 2002.

48. Silver, F.H, Bradica, G. and Seehra, G.P., Structure and function of ligaments, tendons and capsule. In: Repair and Regeneration of Ligaments, Tendon and Joint Capsule, edited by W.R. Walsh, Vol X, Orthopaedic Biology and Medicine Series, Humana Press, Totowa, chapter 1, 2003.

49. Silver, F.H., Biological Materials: Structures, Mechanical Properties and Mechanochemical Transduction, Springer, N.Y., 2003.