Treatment of Large Bone Defects with a Vascularized Periosteal Flap in Combination with Biodegradable Scaffold Seeded with Bone Marrow-Derived Mononuclear Cells: An Experimental Study in Rats.
BACKGROUND
The surgical treatment of large bone defects continues to pose a major challenge in modern trauma and orthopedic surgery. In this study we test the effectiveness of a tissue engineering approach, using three-dimensional (3D) β-tricalcium phosphate (β-TCP) scaffolding plus bone marrow-derived mononuclear cells (BM-MNCs), combined with a vascularized periosteal flap, in a rat femur critical size defect model.


METHODS
Eighty rats were randomly allocated into four equal groups. Under general anesthesia, critical size defects were created on their femurs and were treated with (1) Vascularized periosteal flap alone, (2) Vascularized periosteal flap+β-TCP scaffolding, (3) Vascularized periosteal flap+β-TCP scaffolding+ligated vascular pedicle, and (4) Vascularized periosteal flap+β-TCP scaffolding+BM-MNCs. After 4 and 8 weeks animals were euthanized and the bone defects were harvested for analysis of new bone formation, vascularization, and strength using histology, immunohistology, micro-CT, and biomechanical testing, respectively.


RESULTS
Group 1: (P. flap) Increase in new bone formation and vascularization. Group 2: (P. flap+scaffold) Increase in new bone formation and vascularization. Group 3: (P. flap+scaffold+ligated vascular pedicle) No new bone formation and no vascularization. Group 4: (P. flap+scaffold+BM-MNCs) A significant (p < 0.05) increase was seen in new bone formation, vascularization, and strength in bones treated with flaps, scaffold, and BM-MNCs, when compared with the other treatment groups.


CONCLUSIONS
Combining a vascularized periosteal flap with tissue engineering approach (β-TCP scaffolding and BM-MNC) results in significantly improved bone healing in our rat femur critical size bone defect model.
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Christoph
C
Nau
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Dirk
D
Henrich
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Caroline
C
Seebach
2 Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin der Goethe-Universität , Frankfurt am Main, Germany .
Katrin
K
Schröder
3 Frankfurt Initiative for Regenerative Medicine, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Sammy-Jo
SJ
Fitzsimmons
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Svenja
S
Hankel
3 Frankfurt Initiative for Regenerative Medicine, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
John H
JH
Barker
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Ingo
I
Marzi
1 Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe-University , Frankfurt/Main, Germany .
Johannes
J
Frank
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001861:Bone Regeneration; D005269:Femur / Q000098:blood supply / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010012:Osteogenesis; D010521:Periosteum; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps; D054457:Tissue Scaffolds / Q000737:chemistry*