Nonunion fracture healing: evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model

Barbara Dozza, Francesca Salamanna, Massimiliano Baleani, Gianluca Giavaresi, Annapaola Parrilli, Lorenzo Zani, Enrico Lucarelli, Lucia Martini, Milena Fini, Davide Maria Donati

Research output: Contribution to journalArticle

Abstract

Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (i) develop a new large animal model for bone atrophic nonunion and (ii) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a non-critical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM+MSC) for one day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic and histomorphometric analysis showed the formation of bone callus in DBM group, while the fracture healing appeared at an early stage in DBM+MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM+MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, while MSC do not improve the healing process when cultivated on DBM particles before implantation.

Original languageEnglish
Pages (from-to)1972-1985
Number of pages14
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2018

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Bone Matrix
Fracture Healing
Stem cells
Mesenchymal Stromal Cells
Sheep
Bone
Bone and Bones
Bony Callus
Tibia
Periosteum
Therapeutics
Nails
Amputation
Osteogenesis
Defects
Animal Models

Keywords

  • bone nonunion
  • demineralized bone matrix
  • large animal model
  • mesenchymal stem cells
  • musculoskeletal disorder
  • tissue engineering

Cite this

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title = "Nonunion fracture healing: evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model",
abstract = "Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (i) develop a new large animal model for bone atrophic nonunion and (ii) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a non-critical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM+MSC) for one day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic and histomorphometric analysis showed the formation of bone callus in DBM group, while the fracture healing appeared at an early stage in DBM+MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM+MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, while MSC do not improve the healing process when cultivated on DBM particles before implantation.",
keywords = "bone nonunion, demineralized bone matrix, large animal model, mesenchymal stem cells, musculoskeletal disorder, tissue engineering",
author = "Barbara Dozza and Francesca Salamanna and Massimiliano Baleani and Gianluca Giavaresi and Annapaola Parrilli and Lorenzo Zani and Enrico Lucarelli and Lucia Martini and Milena Fini and Donati, {Davide Maria}",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "9",
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T1 - Nonunion fracture healing: evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model

AU - Dozza, Barbara

AU - Salamanna, Francesca

AU - Baleani, Massimiliano

AU - Giavaresi, Gianluca

AU - Parrilli, Annapaola

AU - Zani, Lorenzo

AU - Lucarelli, Enrico

AU - Martini, Lucia

AU - Fini, Milena

AU - Donati, Davide Maria

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/9

Y1 - 2018/9

N2 - Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (i) develop a new large animal model for bone atrophic nonunion and (ii) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a non-critical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM+MSC) for one day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic and histomorphometric analysis showed the formation of bone callus in DBM group, while the fracture healing appeared at an early stage in DBM+MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM+MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, while MSC do not improve the healing process when cultivated on DBM particles before implantation.

AB - Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (i) develop a new large animal model for bone atrophic nonunion and (ii) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a non-critical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM+MSC) for one day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic and histomorphometric analysis showed the formation of bone callus in DBM group, while the fracture healing appeared at an early stage in DBM+MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM+MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, while MSC do not improve the healing process when cultivated on DBM particles before implantation.

KW - bone nonunion

KW - demineralized bone matrix

KW - large animal model

KW - mesenchymal stem cells

KW - musculoskeletal disorder

KW - tissue engineering

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DO - 10.1002/term.2732

M3 - Article

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JO - Journal of Tissue Engineering and Regenerative Medicine

JF - Journal of Tissue Engineering and Regenerative Medicine

SN - 1932-6254

IS - 9

ER -