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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 bioscaffold denaturation. Calorimetric thermograms of three bioscaffolds at the scan rate of 3°C/min. Note that significant modifications of extracellular matrices are observed in finished bioscaffold products when compared to unprocessed fresh tissues (see Figure 3).
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fig4-2041731413505305: Thermograms of bioscaffold denaturation. Calorimetric thermograms of three bioscaffolds at the scan rate of 3°C/min. Note that significant modifications of extracellular matrices are observed in finished bioscaffold products when compared to unprocessed fresh tissues (see Figure 3).

Mentions: Commercially available scaffolds have calorimetric thermograms that are different from those of their respective unprocessed and/or minimally processed materials (Figure 4). Thermograms of these scaffolds consist of two denaturation peaks, one with a peak width of about 10°C followed by a very broad peak with a width about 40°C. For Strattice and XenMatrix, Peak A is no longer present in finished scaffolds. Peaks B and C at the higher temperature region are still retained in finished scaffolds; however, the changes in denaturation temperature and curve shape (as compared to unprocessed dermis and minimally processed dermis) have demonstrated ECM alterations upon tissue processing (Figures 3 and 4). Strattice has an onset denaturation temperature of 55.5°C ± 0.2°C, and an enthalpy of 56.6 ± 6.7 J/g (n = 5). The onset denaturation temperature of XenMatrix is decreased to a lower temperature (48.3°C ± 0.5°C, n = 6). There is no significant difference in enthalpy between Strattice and XenMatrix. The greatest change is observed in bovine pericardium-derived Veritas (Figures 3 and 4). The onset denaturation temperature of Veritas is decreased to 42.9°C ± 0.2°C, whereas the enthalpy is increased to 56.6 ± 5.1 J/g (n = 3).


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 bioscaffold denaturation. Calorimetric thermograms of three bioscaffolds at the scan rate of 3°C/min. Note that significant modifications of extracellular matrices are observed in finished bioscaffold products when compared to unprocessed fresh tissues (see Figure 3).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

fig4-2041731413505305: Thermograms of bioscaffold denaturation. Calorimetric thermograms of three bioscaffolds at the scan rate of 3°C/min. Note that significant modifications of extracellular matrices are observed in finished bioscaffold products when compared to unprocessed fresh tissues (see Figure 3).
Mentions: Commercially available scaffolds have calorimetric thermograms that are different from those of their respective unprocessed and/or minimally processed materials (Figure 4). Thermograms of these scaffolds consist of two denaturation peaks, one with a peak width of about 10°C followed by a very broad peak with a width about 40°C. For Strattice and XenMatrix, Peak A is no longer present in finished scaffolds. Peaks B and C at the higher temperature region are still retained in finished scaffolds; however, the changes in denaturation temperature and curve shape (as compared to unprocessed dermis and minimally processed dermis) have demonstrated ECM alterations upon tissue processing (Figures 3 and 4). Strattice has an onset denaturation temperature of 55.5°C ± 0.2°C, and an enthalpy of 56.6 ± 6.7 J/g (n = 5). The onset denaturation temperature of XenMatrix is decreased to a lower temperature (48.3°C ± 0.5°C, n = 6). There is no significant difference in enthalpy between Strattice and XenMatrix. The greatest change is observed in bovine pericardium-derived Veritas (Figures 3 and 4). The onset denaturation temperature of Veritas is decreased to 42.9°C ± 0.2°C, whereas the enthalpy is increased to 56.6 ± 5.1 J/g (n = 3).

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