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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

Micro- and ultrastructural features of bioscaffolds. Scanning electron micrographs of three commercially available bioscaffolds: (a–d) Strattice, (e–h): Veritas, and (i–l) XenMatrix. (a, b, e, f, i, and j) Cross sections and (c, d, g, h, k, and l) surface views.
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fig2-2041731413505305: Micro- and ultrastructural features of bioscaffolds. Scanning electron micrographs of three commercially available bioscaffolds: (a–d) Strattice, (e–h): Veritas, and (i–l) XenMatrix. (a, b, e, f, i, and j) Cross sections and (c, d, g, h, k, and l) surface views.

Mentions: The matrix structures of three scaffolds vary significantly (Figure 1). Both Strattice and XenMatrix are derived from porcine dermis with proprietary processing technologies. On histological examination as compared with unprocessed porcine dermis (supplemental Figure S1), the structural integrity of native dermis ECM is retained in Strattice with a uniform architecture of intact collagen bundle structures and the absence of cells. XenMatrix comprises an altered dermal matrix that shows structural dissimilarity from native dermal ECM. Collagen bundles in XenMatrix are fragmented and largely separated. The matrix of pericardium-derived Veritas has a diffuse appearance that lacks the well-defined structural features in unprocessed pericardial ECM. On SEM examination, micrographs reveal more microscopic structural differences among the three scaffolds (Figure 2). Strattice appears as a tightly intertwined and/or interwoven scaffold of collagen bundles, the fibrillar ultra-structures of which are preserved at fibril and fiber levels. Large pores over 50 µm are few between collagen bundles, and are mostly void spaces of blood vessels or removed hair follicles. XenMatrix does not show the architecture of porcine dermal ECM. Collagen fibrils and fibers in XenMatrix are fused together, leading to the complete loss of fibrillar ultra-structures of collagen bundles. Collagen bundles of XenMatrix are condensed, resulting in the formation of many large pores within the matrix. Veritas shows a very loose scaffold of collagen bundles, and large pores over 50 µm are abundant. The fibrillar ultra-structures of collagen bundles in Veritas are also preserved at fibril and fiber levels.


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)

Micro- and ultrastructural features of bioscaffolds. Scanning electron micrographs of three commercially available bioscaffolds: (a–d) Strattice, (e–h): Veritas, and (i–l) XenMatrix. (a, b, e, f, i, and j) Cross sections and (c, d, g, h, k, and l) surface views.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

fig2-2041731413505305: Micro- and ultrastructural features of bioscaffolds. Scanning electron micrographs of three commercially available bioscaffolds: (a–d) Strattice, (e–h): Veritas, and (i–l) XenMatrix. (a, b, e, f, i, and j) Cross sections and (c, d, g, h, k, and l) surface views.
Mentions: The matrix structures of three scaffolds vary significantly (Figure 1). Both Strattice and XenMatrix are derived from porcine dermis with proprietary processing technologies. On histological examination as compared with unprocessed porcine dermis (supplemental Figure S1), the structural integrity of native dermis ECM is retained in Strattice with a uniform architecture of intact collagen bundle structures and the absence of cells. XenMatrix comprises an altered dermal matrix that shows structural dissimilarity from native dermal ECM. Collagen bundles in XenMatrix are fragmented and largely separated. The matrix of pericardium-derived Veritas has a diffuse appearance that lacks the well-defined structural features in unprocessed pericardial ECM. On SEM examination, micrographs reveal more microscopic structural differences among the three scaffolds (Figure 2). Strattice appears as a tightly intertwined and/or interwoven scaffold of collagen bundles, the fibrillar ultra-structures of which are preserved at fibril and fiber levels. Large pores over 50 µm are few between collagen bundles, and are mostly void spaces of blood vessels or removed hair follicles. XenMatrix does not show the architecture of porcine dermal ECM. Collagen fibrils and fibers in XenMatrix are fused together, leading to the complete loss of fibrillar ultra-structures of collagen bundles. Collagen bundles of XenMatrix are condensed, resulting in the formation of many large pores within the matrix. Veritas shows a very loose scaffold of collagen bundles, and large pores over 50 µm are abundant. The fibrillar ultra-structures of collagen bundles in Veritas are also preserved at fibril and fiber levels.

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