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Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration.

Sun WQ, Xu H, Sandor M, Lombardi J - J Tissue Eng (2013)

Bottom Line: Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues.Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation.This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Technology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China ; LifeCell Corporation, Bridgewater, NJ, USA.

ABSTRACT
Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.

No MeSH data available.


Related in: MedlinePlus

Effect of scan rates on bioscaffold denaturation temperatures: (a) Dependence of the onset denaturation temperatures (Td) of bioscaffolds on the scan rate. Arrows indicate the extrapolated intrinsic Td. (b) Thermal stability of bioscaffolds at different temperatures as measured by the duration of time needed to denature ~11% ECM (between the onset and peak temperature). The inset shows the method of calculating the duration of denaturation time.ECM: extracellular matrix; pd-ECM: minimally processed porcine dermis ECM; bp-ECM: minimally processed bovine pericardium ECM; DSC: differential heating calorimetry.
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fig5-2041731413505305: Effect of scan rates on bioscaffold denaturation temperatures: (a) Dependence of the onset denaturation temperatures (Td) of bioscaffolds on the scan rate. Arrows indicate the extrapolated intrinsic Td. (b) Thermal stability of bioscaffolds at different temperatures as measured by the duration of time needed to denature ~11% ECM (between the onset and peak temperature). The inset shows the method of calculating the duration of denaturation time.ECM: extracellular matrix; pd-ECM: minimally processed porcine dermis ECM; bp-ECM: minimally processed bovine pericardium ECM; DSC: differential heating calorimetry.

Mentions: To investigate further the changes in ECM properties after tissue processing, three scaffold products are analyzed with scan rates varying from 0.02°C/min to 50°C/min, which correspond to a change in time scale over three orders of magnitude (Figure 5(a)). The onset denaturation temperature of all ECM samples decreases as the scan rate is reduced, which is consistent with collagen denaturation as an irreversible, time-dependent kinetic process. Minimally processed native ECMs (i.e. porcine dermis ECM and bovine pericardium ECM) have higher onset denaturation temperatures than the derived commercial scaffolds, indicating that all tissue-processing technologies resulted in modifications that destabilize scaffolds (Figure 5(a)). There are significant differences among three commercial scaffolds. The intrinsic onset denaturation temperature (extrapolated to a scan rate of 0.01°C/min) is 55°C for the pd-ECM. The intrinsic onset denaturation temperature is reduced to 51°C and 44°C for Strattice and XenMatrix, respectively. Although the onset denaturation temperature of bovine pericardial ECM is higher than that of porcine dermal ECM, the derived Veritas has the lowest intrinsic onset denaturation temperature (38°C) (Figure 5(a)). Process-caused modification and destabilization are also assessed by calculating the rate of protein denaturation at different onset temperatures (Figure 5(b)). The least stable ECM proteins denature between the onset denaturation temperature and the first peak temperature during a calorimetric measurement. This portion accounts for 11.1% ± 2.4% of the total ECM proteins, assuming that the differential enthalpy is proportional to the mass of denatured ECM proteins. The duration required to denature this portion of ECM proteins increased exponentially as temperature decreased. The ECM stability is in the order of bovine pericardial ECM > porcine dermal ECM > Strattice > XenMatrix > Veritas. The Veritas scaffold does not appear to be sufficiently stable at the human body temperature.


Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration.

Sun WQ, Xu H, Sandor M, Lombardi J - J Tissue Eng (2013)

Effect of scan rates on bioscaffold denaturation temperatures: (a) Dependence of the onset denaturation temperatures (Td) of bioscaffolds on the scan rate. Arrows indicate the extrapolated intrinsic Td. (b) Thermal stability of bioscaffolds at different temperatures as measured by the duration of time needed to denature ~11% ECM (between the onset and peak temperature). The inset shows the method of calculating the duration of denaturation time.ECM: extracellular matrix; pd-ECM: minimally processed porcine dermis ECM; bp-ECM: minimally processed bovine pericardium ECM; DSC: differential heating calorimetry.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC3927753&req=5

fig5-2041731413505305: Effect of scan rates on bioscaffold denaturation temperatures: (a) Dependence of the onset denaturation temperatures (Td) of bioscaffolds on the scan rate. Arrows indicate the extrapolated intrinsic Td. (b) Thermal stability of bioscaffolds at different temperatures as measured by the duration of time needed to denature ~11% ECM (between the onset and peak temperature). The inset shows the method of calculating the duration of denaturation time.ECM: extracellular matrix; pd-ECM: minimally processed porcine dermis ECM; bp-ECM: minimally processed bovine pericardium ECM; DSC: differential heating calorimetry.
Mentions: To investigate further the changes in ECM properties after tissue processing, three scaffold products are analyzed with scan rates varying from 0.02°C/min to 50°C/min, which correspond to a change in time scale over three orders of magnitude (Figure 5(a)). The onset denaturation temperature of all ECM samples decreases as the scan rate is reduced, which is consistent with collagen denaturation as an irreversible, time-dependent kinetic process. Minimally processed native ECMs (i.e. porcine dermis ECM and bovine pericardium ECM) have higher onset denaturation temperatures than the derived commercial scaffolds, indicating that all tissue-processing technologies resulted in modifications that destabilize scaffolds (Figure 5(a)). There are significant differences among three commercial scaffolds. The intrinsic onset denaturation temperature (extrapolated to a scan rate of 0.01°C/min) is 55°C for the pd-ECM. The intrinsic onset denaturation temperature is reduced to 51°C and 44°C for Strattice and XenMatrix, respectively. Although the onset denaturation temperature of bovine pericardial ECM is higher than that of porcine dermal ECM, the derived Veritas has the lowest intrinsic onset denaturation temperature (38°C) (Figure 5(a)). Process-caused modification and destabilization are also assessed by calculating the rate of protein denaturation at different onset temperatures (Figure 5(b)). The least stable ECM proteins denature between the onset denaturation temperature and the first peak temperature during a calorimetric measurement. This portion accounts for 11.1% ± 2.4% of the total ECM proteins, assuming that the differential enthalpy is proportional to the mass of denatured ECM proteins. The duration required to denature this portion of ECM proteins increased exponentially as temperature decreased. The ECM stability is in the order of bovine pericardial ECM > porcine dermal ECM > Strattice > XenMatrix > Veritas. The Veritas scaffold does not appear to be sufficiently stable at the human body temperature.

Bottom Line: Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues.Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation.This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Technology, School of Medical Instruments and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China ; LifeCell Corporation, Bridgewater, NJ, USA.

ABSTRACT
Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.

No MeSH data available.


Related in: MedlinePlus