Silk based biomaterials to heal critical sized femur defects

L. Meinel, O. Betz, R. Fajardo, S. Hofmann, A. Nazarian, E. Cory, M. Hilbe, J. McCool, R. Langer, G. Vunjak-Novakovic, H.P. Merkle, B. Rechenberg, von, D.L. Kaplan, C. Kirker-Head

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Abstract

Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P <0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P <0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.
Original languageEnglish
Pages (from-to)922-931
Number of pages10
JournalBone
Volume39
Issue number4
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Silk
Biocompatible Materials
Femur
Mesenchymal Stromal Cells
Osteogenesis
Bone and Bones
Weight-Bearing
Thigh
Fibroins
Nude Rats
Calcium
Autografts
Torque
Allografts
Alkaline Phosphatase
Fibroblasts
Cytokines
Weights and Measures

Cite this

Meinel, L., Betz, O., Fajardo, R., Hofmann, S., Nazarian, A., Cory, E., ... Kirker-Head, C. (2006). Silk based biomaterials to heal critical sized femur defects. Bone, 39(4), 922-931. https://doi.org/10.1016/j.bone.2006.04.019
Meinel, L. ; Betz, O. ; Fajardo, R. ; Hofmann, S. ; Nazarian, A. ; Cory, E. ; Hilbe, M. ; McCool, J. ; Langer, R. ; Vunjak-Novakovic, G. ; Merkle, H.P. ; Rechenberg, von, B. ; Kaplan, D.L. ; Kirker-Head, C. / Silk based biomaterials to heal critical sized femur defects. In: Bone. 2006 ; Vol. 39, No. 4. pp. 922-931.
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abstract = "Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P <0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P <0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.",
author = "L. Meinel and O. Betz and R. Fajardo and S. Hofmann and A. Nazarian and E. Cory and M. Hilbe and J. McCool and R. Langer and G. Vunjak-Novakovic and H.P. Merkle and {Rechenberg, von}, B. and D.L. Kaplan and C. Kirker-Head",
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Meinel, L, Betz, O, Fajardo, R, Hofmann, S, Nazarian, A, Cory, E, Hilbe, M, McCool, J, Langer, R, Vunjak-Novakovic, G, Merkle, HP, Rechenberg, von, B, Kaplan, DL & Kirker-Head, C 2006, 'Silk based biomaterials to heal critical sized femur defects', Bone, vol. 39, no. 4, pp. 922-931. https://doi.org/10.1016/j.bone.2006.04.019

Silk based biomaterials to heal critical sized femur defects. / Meinel, L.; Betz, O.; Fajardo, R.; Hofmann, S.; Nazarian, A.; Cory, E.; Hilbe, M.; McCool, J.; Langer, R.; Vunjak-Novakovic, G.; Merkle, H.P.; Rechenberg, von, B.; Kaplan, D.L.; Kirker-Head, C.

In: Bone, Vol. 39, No. 4, 2006, p. 922-931.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Silk based biomaterials to heal critical sized femur defects

AU - Meinel, L.

AU - Betz, O.

AU - Fajardo, R.

AU - Hofmann, S.

AU - Nazarian, A.

AU - Cory, E.

AU - Hilbe, M.

AU - McCool, J.

AU - Langer, R.

AU - Vunjak-Novakovic, G.

AU - Merkle, H.P.

AU - Rechenberg, von, B.

AU - Kaplan, D.L.

AU - Kirker-Head, C.

PY - 2006

Y1 - 2006

N2 - Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P <0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P <0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.

AB - Bone auto- and allografts have inherent drawbacks, therefore the treatment of non-unions and critical size defects in load bearing long bones would benefit from the use of osteopromotive biodegradable, biocompatible and mechanically durable matrices to enhance migration or delivery of cell populations and/or morphogens/cytokines. Silk fibroin biomaterial scaffolds were evaluated as osteopromotive matrices in critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over 8 weeks in vivo: silk scaffolds (SS) with human mesenchymal stem cells (hMSCs) that had previously been differentiated along an osteoblastic lineage in vitro (group I; pdHMSC/SS); SS with undifferentiated hMSCs (group II; udHMSC/SS); SS alone (group III; SS); and empty defects (group IV). When hMSCs were cultured in vitro in osteogenic medium for 5 weeks, bone formation was characterized with bimodal peak activities for alkaline phosphatase at 2 and 4 weeks. Calcium deposition started after 1 week and progressively increased to peak at 4 weeks, reaching cumulative levels of deposited calcium at 16 mug per mg scaffold wet weight. In vivo osteogenesis was characterized by almost bridged defects with newly formed bone after 8 weeks in group I. Significantly (P <0.01) greater bone volumes were observed with the pdHMSC/SS (group I) implants than with groups II, III or IV. These three groups failed to induce substantial new bone formation and resulted in the ingrowth of cells with fibroblast-like morphology into the defect zone. The implantation of pdHMSC/SS resulted in significantly (P <0.05) greater maximal load and torque when compared to the other treatment regimens. The pdHMSC/SS implants demonstrated osteogenic ability in vitro and capacity to thrive towards the healing of critical size femoral segmental defects in vivo. Thus, these new constructs provide an alternative protein-based biomaterial for load bearing applications.

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DO - 10.1016/j.bone.2006.04.019

M3 - Article

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VL - 39

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Meinel L, Betz O, Fajardo R, Hofmann S, Nazarian A, Cory E et al. Silk based biomaterials to heal critical sized femur defects. Bone. 2006;39(4):922-931. https://doi.org/10.1016/j.bone.2006.04.019