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 language | English |
|---|---|
| Pages (from-to) | 1972-1985 |
| Number of pages | 14 |
| Journal | Journal of Tissue Engineering and Regenerative Medicine |
| Volume | 12 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2018 |
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Keywords
- bone nonunion
- demineralized bone matrix
- large animal model
- mesenchymal stem cells
- musculoskeletal disorder
- tissue engineering
Cite this
Nonunion fracture healing: evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model. / Dozza, Barbara; Salamanna, Francesca; Baleani, Massimiliano; Giavaresi, Gianluca; Parrilli, Annapaola; Zani, Lorenzo; Lucarelli, Enrico; Martini, Lucia; Fini, Milena; Donati, Davide Maria.
In: Journal of Tissue Engineering and Regenerative Medicine, Vol. 12, No. 9, 09.2018, p. 1972-1985.Research output: Contribution to journal › Article
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TY - JOUR
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
U2 - 10.1002/term.2732
DO - 10.1002/term.2732
M3 - Article
C2 - 30044550
VL - 12
SP - 1972
EP - 1985
JO - Journal of Tissue Engineering and Regenerative Medicine
JF - Journal of Tissue Engineering and Regenerative Medicine
SN - 1932-6254
IS - 9
ER -