Secondary Logo

Journal Logo

Osteogenic Potential of Polymer-Bound Bone Morphogenetic Protein-2 on MC3T3-E1 Two-Dimensional Cell Cultures

Pereira, Clifford T., M.B.B.S.; Huang, Weibiao, Ph.D.; Sayer, Gregory, B.A., B.S.; Jarrahy, Reza, M.D.; Rudkin, George, M.D.; Miller, Timothy A., M.D.

Plastic and Reconstructive Surgery: December 2009 - Volume 124 - Issue 6 - p 2199-2200
doi: 10.1097/PRS.0b013e3181bcf5ff
LETTERS
Free

Plastic Surgery Molecular Biology Laboratory, Department of Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, Calif.

Correspondence to Dr. Pereira, Plastic Surgery Molecular Biology Laboratory, Department of Veterans Affairs, Greater Los Angeles Healthcare System, Building 114, Room 221, 11301 Wilshire Boulevard, Los Angeles, Calif. 90073

Back to Top | Article Outline

Sir:

We read with interest the recent article by Gharibjanian et al.1 regarding the osteogenic potential of bone morphogenetic protein-2 (BMP-2) covalently bound to poly(lactic-co-glycolic acid) and polycaprolactone, on MC3T3-E1 preosteoblast cells in two-dimensional cultures. We write to provide additional comments and perspectives on the study. An up-regulation was noted in alkaline phosphatase and osteocalcin activity at day 4 in cells cultured on poly(lactic-co-glycolic acid) plus BMP-2, but not in cells cultured on polycaprolactone plus BMP-2 or polycaprolactone alone (Fig. 1). Osteocalcin and alkaline phosphatase up-regulation was higher in the control group compared with the polycaprolactone plus BMP-2 group or the polycaprolactone group (Fig. 1) at day 4. This was despite the fact that the peak in BMP-2 release from polymers (Fig. 4) occurring at day 2 was higher in the polycaprolactone plus BMP-2 group (approximately 300 pg) compared with poly(lactic-co-glycolic acid) plus BMP-2 (approximately 150 pg). We wonder whether this occurred because of cell adhesion differences on the polymer surface secondary to differential topographic surface changes in polycaprolactone compared with poly(lactic-co-glycolic acid) or controls. Variation in cell adhesion based on surface topography of biodegradable polymers such as poly(lactic acid), poly(lactic-co-glycolic acid), and polycaprolactone is well recognized.2 Also, extremes of pH such as exposure to chloric acid or sodium hydroxide have previously been shown to nanostructure these polymer surfaces and alter cell-surface mechanical stress interactions.2,3 Cytoskeletal stress is known to influence osteoinduction in osteoprecursor cells such as MC3T3-E1 cells.4 It is plausible therefore that exposure to 6N sulfuric acid during the covalent binding of BMP-2 could have altered the polycaprolactone surface, causing reduced cell adhesion that in turn decreased osteogenesis.

It is interesting that after the initial surge in BMP-2 release from polycaprolactone, the levels were subtherapeutic from days 6 to 10, with an inexplicable late peak at day 12 (Fig. 4). This late peak could be attributable to chemical degradation of the polycaprolactone. We wonder whether the authors conducted any studies to investigate this phenomenon and the structural integrity of the polycaprolactone surface. If the acid hydrolysis essential to covalent bonding process indeed causes chemical degradation of polycaprolactone, this would have obvious implications in future clinical use where structural integrity of scaffolds in bone reconstruction is of utmost importance.

Finally, our experience with the use of mesenchymal stem cells in osseous tissue engineering indicates a differential response to growth factors such as BMP-2 in three-dimensional versus two-dimensional cultures.5 Because three-dimensional cultures mimic in vivo conditions more closely than two-dimensional cultures, it would be interesting to see similar studies on three-dimensional scaffolds. Our previous work also underscored the necessity of osteoinductive agents such as BMP-2 for robust osteogenesis in three dimensions.5 The delivery of osteoinductive agents by means of bioactive scaffolds is an innovative technique. We compliment the authors on a nicely conducted study and thank the Editor for the opportunity to share our thoughts on this article.

Clifford T. Pereira, M.B.B.S.

Weibiao Huang, Ph.D.

Gregory Sayer, B.A., B.S.

Reza Jarrahy, M.D.

George Rudkin, M.D.

Timothy A. Miller, M.D.

Plastic Surgery Molecular Biology Laboratory

Department of Veterans Affairs

Greater Los Angeles Healthcare System

Los Angeles, Calif.

Back to Top | Article Outline

DISCLOSURE

The authors have no financial interest or commercial association with any of the subject matter or products mentioned in this letter.

Back to Top | Article Outline

REFERENCES

1. Gharibjanian NA, Chua WC, Dhar S, et al. Release kinetics of polymer-bound bone morphogenetic protein-2 and its effects on the osteogenic expression of MC3T3-E1 osteoprecursor cells. Plast Reconstr Surg. 2009;123:1169–1177.
2. Lee SJ, Khang G, Lee YM, Lee HB. Interactions of human chondrocytes and NIH/3T3 fibroblasts on chloric acid-treated biodegradable polymer surfaces. J Biomater Sci Polym Ed. 2002;13:197–212.
3. Marletta G, Ciapetti G, Satriano C, Perut F, Sarerno M, Baldini N. Improved osteogenic differentiation of human marrow stromal cells cultured on ion-induced chemically structured poly-epsilon-caprolactone. Biomaterials 2007;28:1132–1140.
4. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 2004;6:483–495.
5. Huang W, Carlsen B, Wulur I, et al. BMP-2 exerts differential effects on differentiation of rabbit bone marrow stromal cells grown in two dimensional and three-dimensional systems and is required for in vitro bone formation in a PLGA scaffold. Exp Cell Res. 2004;299:325–334.

Section Description

GUIDELINES

Letters to the Editor, discussing material recently published in the Journal, are welcome. They will have the best chance of acceptance if they are received within 8 weeks of an article's publication. Letters to the Editor may be published with a response from the authors of the article being discussed. Discussions beyond the initial letter and response will not be published. Letters submitted pertaining to published Discussions of articles will not be printed. Letters to the Editor are not usually peer reviewed, but the Journal may invite replies from the authors of the original publication. All Letters are published at the discretion of the Editor.

Authors will be listed in the order in which they appear in the submission. Letters should be submitted electronically via PRS' enkwell, at www.editorialmanager.com/prs/.

We reserve the right to edit Letters to meet requirements of space and format. Any financial interests relevant to the content of the correspondence must be disclosed. Submission of a Letter constitutes permission for the American Society of Plastic Surgeons and its licensees and asignees to publish it in the Journal and in any other form or medium.

The views, opinions, and conclusions expressed in the Letters to the Editor represent the personal opinions of the individual writers and not those of the publisher, the Editorial Board, or the sponsors of the Journal. Any stated views, opinions, and conclusions do not reflect the policy of any of the sponsoring organizations or of the institutions with which the writer is affiliated, and the publisher, the Editorial Board, and the sponsoring organizations assume no responsibility for the content of such correspondence.

©2009American Society of Plastic Surgeons