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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

Thermograms of unprocessed animal tissues. Calorimetric thermograms of fresh bovine pericardium and porcine dermis at the scan rate of 3°C/min. Three independent test curves are superimposed for each material type. Td denotes the onset denaturation temperature.
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fig3-2041731413505305: Thermograms of unprocessed animal tissues. Calorimetric thermograms of fresh bovine pericardium and porcine dermis at the scan rate of 3°C/min. Three independent test curves are superimposed for each material type. Td denotes the onset denaturation temperature.

Mentions: The DSC thermogram of fresh porcine dermis consists of multiple overlapping endothermic peaks between 20°C and 120°C (Figure 3). Upon heating at a scan rate of 3°C/min, protein denaturation starts at 54.0°C ± 0.2°C, and the event ends when temperature reaches around 90°C, with a total enthalpic value of 54.8 ± 2.4 J/g (n = 9). The complex thermogram of unprocessed porcine dermis consists of three separate denaturation events (Peaks A, B, and C), which account for 16.7% ± 3.0%, 41.1% ± 4.8%, and 42.2% ± 4.0%, respectively (supplemental Figure S2). Peak A disappears after cell lysis and washing in saline or PBS. The pd-ECM retains Peaks B and C, without any change in their onset and peak temperatures. The DSC thermogram of fresh bovine pericardium starts at a much higher temperature, 63.0°C ± 0.5°C, with a smaller enthalpic value of 45.6 ± 4.4 J/g (n = 10) (Figure 3). It appears that the thermogram of bovine pericardium consists of only Peaks B and C between 20°C and 120°C, and Peak A in the lower temperature region is insignificant. The minimally processed bovine pericardial ECM has essentially the same DSC thermogram as fresh bovine pericardium (data not shown).


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)

Thermograms of unprocessed animal tissues. Calorimetric thermograms of fresh bovine pericardium and porcine dermis at the scan rate of 3°C/min. Three independent test curves are superimposed for each material type. Td denotes the onset denaturation temperature.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

fig3-2041731413505305: Thermograms of unprocessed animal tissues. Calorimetric thermograms of fresh bovine pericardium and porcine dermis at the scan rate of 3°C/min. Three independent test curves are superimposed for each material type. Td denotes the onset denaturation temperature.
Mentions: The DSC thermogram of fresh porcine dermis consists of multiple overlapping endothermic peaks between 20°C and 120°C (Figure 3). Upon heating at a scan rate of 3°C/min, protein denaturation starts at 54.0°C ± 0.2°C, and the event ends when temperature reaches around 90°C, with a total enthalpic value of 54.8 ± 2.4 J/g (n = 9). The complex thermogram of unprocessed porcine dermis consists of three separate denaturation events (Peaks A, B, and C), which account for 16.7% ± 3.0%, 41.1% ± 4.8%, and 42.2% ± 4.0%, respectively (supplemental Figure S2). Peak A disappears after cell lysis and washing in saline or PBS. The pd-ECM retains Peaks B and C, without any change in their onset and peak temperatures. The DSC thermogram of fresh bovine pericardium starts at a much higher temperature, 63.0°C ± 0.5°C, with a smaller enthalpic value of 45.6 ± 4.4 J/g (n = 10) (Figure 3). It appears that the thermogram of bovine pericardium consists of only Peaks B and C between 20°C and 120°C, and Peak A in the lower temperature region is insignificant. The minimally processed bovine pericardial ECM has essentially the same DSC thermogram as fresh bovine pericardium (data not shown).

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