Pretreatment of periosteum with TGF-β1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits

Olivos-Meza, A.; Fitzsimmons, J.S.; Casper, M.E.; Chen, Q.; An, K.-N.; Ruesink, T.J.; O’Driscoll, S.W.; Reinholz, G.G.

doi:10.1016/j.joca.2010.06.003

« Previous Next »Osteoarthritis and Cartilage
Volume 18, Issue 9 , Pages 1183-1191, September 2010

Pretreatment of periosteum with TGF-β1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits

A. Olivos-Meza
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
J.S. Fitzsimmons
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
M.E. Casper
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Q. Chen
- Department of Orthopedic Surgery, Orthopedic Biomechanics Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
K.-N. An
- Department of Orthopedic Surgery, Orthopedic Biomechanics Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
T.J. Ruesink
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
S.W. O’Driscoll
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
G.G. Reinholz
- Department of Orthopedic Surgery, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
- Address correspondence and reprint requests to: Gregory G. Reinholz, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Received 5 October 2009; accepted 17 June 2010. published online 14 July 2010.

Summary

Objective

To compare the efficacy of in situ transforming growth factor-beta1 (TGF-β1)-pretreated periosteum to untreated periosteum for regeneration of osteochondral tissue in rabbits.

Methods

In the pretreatment group, 12 month-old New Zealand white rabbits received subperiosteal injections of 200ng of TGF-β1 percutaneously in the medial side of the proximal tibia, 7 days prior to surgery. Control rabbits received no treatment prior surgery. Osteochondral transverse defects measuring 5mm proximal to distal and spanning the entire width of the patellar groove were created and repaired with untreated or TGF-β1-pretreated periosteal grafts. Post-operatively the rabbits resumed normal cage activity for 6 weeks.

Results

Complete filling of the defects with regenerated tissue was observed in both the TGF-β1-pretreated and control groups with reformation of the original contours of the patellar groove. The total histological score (modified O’Driscoll) in the TGF-β1-pretreated group, 20 (95% Confidence Interval (CI), 19–21), was significantly higher (P=0.0001) than the control group, 18 (16–19). The most notable improvements were in structural integrity and subchondral bone regeneration. No significant differences in glycosaminoglycan or type II collagen content, or equilibrium modulus were found between the surgical groups. The cambium of the periosteum regenerated at the graft harvest site was significantly thicker (P=0.0065) in the TGF-β1-pretreated rabbits, 121μm (94–149), compared to controls, 74μm (52–96), after 6 weeks.

Conclusions

This study demonstrates that in situ pretreatment of periosteum with TGF-β1 improves osteochondral tissue regeneration at 6-weeks post-op compared to untreated periosteum in 12 month-old rabbits.

Keywords: Bone, Cartilage, Chondrogenesis, Joints, Periosteum, Regenerative medicine, Tissue engineering, Transforming growth factor-beta