Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology, 2000
Journal of biomedical materials research. Part A, Jan 10, 2016
Numerous tests have been used to elucidate mechanical properties of tissues and implants includin... more Numerous tests have been used to elucidate mechanical properties of tissues and implants including tensile, compressive, shear, hydrostatic compression and three-point bending in one or more axial directions. The development of a non-destructive test that could be applied to tissues and materials in vivo would promote the analysis of tissue pathology as well as the design of implant materials. The purpose of this paper is to present the results of preliminary studies demonstrating non-destructive in vitro testing of a tissue model, decellularized human dermis, and a model implant, silicone rubber, using a combination of optical coherence tomography (OCT) and vibrational analysis. The results presented suggest that non-destructive vibrational testing of tissues and materials can be used to determine the modulus of polymeric materials and the results are similar to those found using tensile stress-strain measurements. The advantage of this method is that the modulus can obtained from ...
The properties of collagen films crosslinked by physical and chemical techniques were compared to... more The properties of collagen films crosslinked by physical and chemical techniques were compared to the properties of films crosslinked with glutaraldehyde (GTA). Physical techniques studied include exposure to short wave (254 nm) u.v. irradiation and severe dehydration. Chemical techniques studied include immersion of collagen films in aqueous solutions of cyanamide or GTA. Collagen films exposed to combinations of aqueous solutions of cyanamide and severe dehydration had moduli of elasticity, swelling ratios and resistance to bacterial collagenase similar to films crosslinked with GTA. Theoretical calculations based on amino acid composition indicate that approximately seven times as many amino acid residues are capable of forming crosslinks using cyanamide or severe dehydration procedures as compared to GTA crosslinking. In addition, using severe dehydration or cyanamide forms crosslinks involving both amino and carboxyl residues which may allow these procedures to act synergistically. Based on our studies this two-step procedure effectively crosslinks collagen-based biomaterials while the only by-product of this reaction is water-soluble urea. Preliminary biocompatibility studies suggest that this crosslinking procedure may allow for pronounced tissue ingrowth.
Rapid fibroblast ingrowth and collagen deposition occurs in a reconstituted type I collagen matri... more Rapid fibroblast ingrowth and collagen deposition occurs in a reconstituted type I collagen matrix that is implanted on full-thickness excised animal dermal wounds. The purpose of this study is to evaluate the effects of direct current stimulation on dermal fibroblast ingrowth using carbon fiber electrodes incorporated into a collagen sponge matrix. Preliminary results suggest that fibroblast ingrowth and collagen fiber alignment are increased in collagen sponges stimulated with direct currents between 20 and 100 microA. Maximum fibroblast ingrowth into the collagen sponge is observed near the cathode at a current of 100 microA. These results suggest that electrical stimulation combined with a collagen matrix may be a method to enhance the healing of chronic dermal wounds.
Fibrous collagen networks are the major elements that provide mechanical integrity to tissues; th... more Fibrous collagen networks are the major elements that provide mechanical integrity to tissues; they are composed of fiber forming collagens in combination with proteoglycans (PGs). Using uniaxial tensile tests we have studied the viscoelastic mechanical properties of rat tail tendon (RTT) fibers and self-assembled collagen fibers that were stored at 22 degrees C and 1 atm of pressure. Our results indicate that storage of RTT and self-assembled type I collagen fibers results in increased elastic and viscous components of the stress-strain behavior consistent with the hypothesis that storage causes the introduction of crosslinks. Analysis of the elastic and viscous mechanical data suggests that the elastic constant of the collagen molecule in RTT is about 7.7 GPa. Measurement of the viscous component of the stress-strain curves for RTTs and self-assembled collagen fibers suggests that PGs may increase the viscous component and effectively increase the collagen fibril length.
The vertebrate skeletal system undergoes adaptation in response to external forces, but the relat... more The vertebrate skeletal system undergoes adaptation in response to external forces, but the relation between the skeletal changes and such forces is not understood. In this context, the variation in the amount and location of calcification has been compared with changes in mechanical properties of the normally mineralizing turkey gastrocnemius tendon using ash weight measurements, X-ray radiography, and mechanical testing. Radiographic evidence from 12-to 17-week-old birds showed calcification in only portions of gastrocnemius tendons proximal to the tarsometatarsal joint. Mechanical testing of these dissected proximal regions demonstrated an increased ultimate stress and modulus and a decreased maximum strain that appeared to parallel calcification. Further, stress-strain curves of portions of uncalcified turkey gastrocnemius tendon were shaped similar to those of other typical unmineralized tendon curves while highly calcified tendons yielded curves resembling those of bone. The proximal portions of the gastrocnemius where mineralization begins were observed to have a decreased tendon cross-sectional area compared with distal portions which do not mineralize. Based on the resultant measures of mineral content and location and mechanical properties, it is hypothesized that increased calcification is a result of increased stresses at certain locations of the tendon, perhaps the consequence of the natural forces exerted by the large leg muscles of the bird into which the gastrocnemius inserts. More specifically, tendon calcification may be the result of stress-induced exposure of charged sites on the surfaces of collagen molecules, fibrils, or fibers so that deposition of mineral and subsequent mechanical reinforcement occur in the tissue. The concept of stressinduced calcification of avian tendon is found to be consistent with other examples of biological mineralization and supports the view that vertebrate calcification is an adaptive process mediated in part by the accommodation of natural or applied forces. the precise means responsible for calcium deposition has not yet been determined. Among many possibilitic\. thc induction of mineralization in different systems has been considered in part the result of mcchanical forces. In this context, there is substantial relatively recent litcraturc ;iddressing such forces and modeling thcir cffccts o n biological tissues including bone" -3) and cartilage.'"
Stress-relaxation tests were performed at successive strain levels on strips of human aorta, skin... more Stress-relaxation tests were performed at successive strain levels on strips of human aorta, skin, psoas tendon, dura mater, and pericardium. The elastic fraction, the equilibrium force divided by the initial force, was calculated at each strain increment. In the aorta, the elastic fraction decreased with strain and was modeled as the transfer of stress from elastic to collagen fibers, while in skin it increased with strain, probably due to the rearrangement of individual collagen fiber orientations, resulting in an aligned collagen network at high strains. The strain-independent elastic fractions for tendon, dura mater, and pericardium were similar, and approximately equal to the values found for aorta and skin at high strains. It was hypothesized that the elastic fraction is related to the type of fiber loaded, and the tissue geometry. This analysis may be useful in studying disease-induced changes in the mechanical properties of connective tissues.
Journal of Long Term Effects of Medical Implants, Feb 1, 1992
Collagen has been used as a substrate for growth of cells derived from skin and cardiovascular ti... more Collagen has been used as a substrate for growth of cells derived from skin and cardiovascular tissue. Experimental results reported in the literature suggest that cell differentiation and orientation is enhanced in the presence of collagen. Extensive progress in cultivation of autogenous and allogeneic cells in vitro on collagen has led to advances in the transplantation of cultured materials. The purpose of this paper is to review the literature regarding cell culture on collagen substrates and to analyze the state of knowledge concerning the long-term effects. In the area of skin, long-term replacement of tissue has been studied extensively. Progress in this area has led to the development of technologies that will be used in the future for producing replacements for a wide variety of tissues and organs.
Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology, 2000
Journal of biomedical materials research. Part A, Jan 10, 2016
Numerous tests have been used to elucidate mechanical properties of tissues and implants includin... more Numerous tests have been used to elucidate mechanical properties of tissues and implants including tensile, compressive, shear, hydrostatic compression and three-point bending in one or more axial directions. The development of a non-destructive test that could be applied to tissues and materials in vivo would promote the analysis of tissue pathology as well as the design of implant materials. The purpose of this paper is to present the results of preliminary studies demonstrating non-destructive in vitro testing of a tissue model, decellularized human dermis, and a model implant, silicone rubber, using a combination of optical coherence tomography (OCT) and vibrational analysis. The results presented suggest that non-destructive vibrational testing of tissues and materials can be used to determine the modulus of polymeric materials and the results are similar to those found using tensile stress-strain measurements. The advantage of this method is that the modulus can obtained from ...
The properties of collagen films crosslinked by physical and chemical techniques were compared to... more The properties of collagen films crosslinked by physical and chemical techniques were compared to the properties of films crosslinked with glutaraldehyde (GTA). Physical techniques studied include exposure to short wave (254 nm) u.v. irradiation and severe dehydration. Chemical techniques studied include immersion of collagen films in aqueous solutions of cyanamide or GTA. Collagen films exposed to combinations of aqueous solutions of cyanamide and severe dehydration had moduli of elasticity, swelling ratios and resistance to bacterial collagenase similar to films crosslinked with GTA. Theoretical calculations based on amino acid composition indicate that approximately seven times as many amino acid residues are capable of forming crosslinks using cyanamide or severe dehydration procedures as compared to GTA crosslinking. In addition, using severe dehydration or cyanamide forms crosslinks involving both amino and carboxyl residues which may allow these procedures to act synergistically. Based on our studies this two-step procedure effectively crosslinks collagen-based biomaterials while the only by-product of this reaction is water-soluble urea. Preliminary biocompatibility studies suggest that this crosslinking procedure may allow for pronounced tissue ingrowth.
Rapid fibroblast ingrowth and collagen deposition occurs in a reconstituted type I collagen matri... more Rapid fibroblast ingrowth and collagen deposition occurs in a reconstituted type I collagen matrix that is implanted on full-thickness excised animal dermal wounds. The purpose of this study is to evaluate the effects of direct current stimulation on dermal fibroblast ingrowth using carbon fiber electrodes incorporated into a collagen sponge matrix. Preliminary results suggest that fibroblast ingrowth and collagen fiber alignment are increased in collagen sponges stimulated with direct currents between 20 and 100 microA. Maximum fibroblast ingrowth into the collagen sponge is observed near the cathode at a current of 100 microA. These results suggest that electrical stimulation combined with a collagen matrix may be a method to enhance the healing of chronic dermal wounds.
Fibrous collagen networks are the major elements that provide mechanical integrity to tissues; th... more Fibrous collagen networks are the major elements that provide mechanical integrity to tissues; they are composed of fiber forming collagens in combination with proteoglycans (PGs). Using uniaxial tensile tests we have studied the viscoelastic mechanical properties of rat tail tendon (RTT) fibers and self-assembled collagen fibers that were stored at 22 degrees C and 1 atm of pressure. Our results indicate that storage of RTT and self-assembled type I collagen fibers results in increased elastic and viscous components of the stress-strain behavior consistent with the hypothesis that storage causes the introduction of crosslinks. Analysis of the elastic and viscous mechanical data suggests that the elastic constant of the collagen molecule in RTT is about 7.7 GPa. Measurement of the viscous component of the stress-strain curves for RTTs and self-assembled collagen fibers suggests that PGs may increase the viscous component and effectively increase the collagen fibril length.
The vertebrate skeletal system undergoes adaptation in response to external forces, but the relat... more The vertebrate skeletal system undergoes adaptation in response to external forces, but the relation between the skeletal changes and such forces is not understood. In this context, the variation in the amount and location of calcification has been compared with changes in mechanical properties of the normally mineralizing turkey gastrocnemius tendon using ash weight measurements, X-ray radiography, and mechanical testing. Radiographic evidence from 12-to 17-week-old birds showed calcification in only portions of gastrocnemius tendons proximal to the tarsometatarsal joint. Mechanical testing of these dissected proximal regions demonstrated an increased ultimate stress and modulus and a decreased maximum strain that appeared to parallel calcification. Further, stress-strain curves of portions of uncalcified turkey gastrocnemius tendon were shaped similar to those of other typical unmineralized tendon curves while highly calcified tendons yielded curves resembling those of bone. The proximal portions of the gastrocnemius where mineralization begins were observed to have a decreased tendon cross-sectional area compared with distal portions which do not mineralize. Based on the resultant measures of mineral content and location and mechanical properties, it is hypothesized that increased calcification is a result of increased stresses at certain locations of the tendon, perhaps the consequence of the natural forces exerted by the large leg muscles of the bird into which the gastrocnemius inserts. More specifically, tendon calcification may be the result of stress-induced exposure of charged sites on the surfaces of collagen molecules, fibrils, or fibers so that deposition of mineral and subsequent mechanical reinforcement occur in the tissue. The concept of stressinduced calcification of avian tendon is found to be consistent with other examples of biological mineralization and supports the view that vertebrate calcification is an adaptive process mediated in part by the accommodation of natural or applied forces. the precise means responsible for calcium deposition has not yet been determined. Among many possibilitic\. thc induction of mineralization in different systems has been considered in part the result of mcchanical forces. In this context, there is substantial relatively recent litcraturc ;iddressing such forces and modeling thcir cffccts o n biological tissues including bone" -3) and cartilage.'"
Stress-relaxation tests were performed at successive strain levels on strips of human aorta, skin... more Stress-relaxation tests were performed at successive strain levels on strips of human aorta, skin, psoas tendon, dura mater, and pericardium. The elastic fraction, the equilibrium force divided by the initial force, was calculated at each strain increment. In the aorta, the elastic fraction decreased with strain and was modeled as the transfer of stress from elastic to collagen fibers, while in skin it increased with strain, probably due to the rearrangement of individual collagen fiber orientations, resulting in an aligned collagen network at high strains. The strain-independent elastic fractions for tendon, dura mater, and pericardium were similar, and approximately equal to the values found for aorta and skin at high strains. It was hypothesized that the elastic fraction is related to the type of fiber loaded, and the tissue geometry. This analysis may be useful in studying disease-induced changes in the mechanical properties of connective tissues.
Journal of Long Term Effects of Medical Implants, Feb 1, 1992
Collagen has been used as a substrate for growth of cells derived from skin and cardiovascular ti... more Collagen has been used as a substrate for growth of cells derived from skin and cardiovascular tissue. Experimental results reported in the literature suggest that cell differentiation and orientation is enhanced in the presence of collagen. Extensive progress in cultivation of autogenous and allogeneic cells in vitro on collagen has led to advances in the transplantation of cultured materials. The purpose of this paper is to review the literature regarding cell culture on collagen substrates and to analyze the state of knowledge concerning the long-term effects. In the area of skin, long-term replacement of tissue has been studied extensively. Progress in this area has led to the development of technologies that will be used in the future for producing replacements for a wide variety of tissues and organs.
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Papers by Frederick Silver