TY - JOUR
T1 - Nonunion fracture healing
T2 - 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 - Funding Information:
This work was partially supported by Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia‐Romagna “Bruno Ubertini” (IZSLER), Brescia, Italy. The authors wish to thank Luigi Lena for the artwork and Ryan Rogers for editorial assistance.
Funding Information:
This work was partially supported by Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia-Romagna “Bruno Ubertini” (IZSLER), Brescia, Italy. The authors wish to thank Luigi Lena for the artwork and Ryan Rogers for editorial assistance.
Publisher Copyright:
© 2018 John Wiley & Sons, Ltd.
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 (a) develop a new large animal model for bone atrophic nonunion and (b) 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 noncritical, 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 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas 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, whereas 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 (a) develop a new large animal model for bone atrophic nonunion and (b) 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 noncritical, 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 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas 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, whereas 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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U2 - 10.1002/term.2732
DO - 10.1002/term.2732
M3 - Article
C2 - 30044550
AN - SCOPUS:85052484864
SN - 1932-6254
VL - 12
SP - 1972
EP - 1985
JO - Journal of Tissue Engineering and Regenerative Medicine
JF - Journal of Tissue Engineering and Regenerative Medicine
IS - 9
ER -