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Programmed Healing of Membranous Bone in the Fetal Lamb

Shahinian, Hrayr MD*; Levine, Jamie P. MD; Bradley, James P. MD; O'Hara, Catherine BA; McCormick, Susan A. DDS§; Kim, Yoonah DDS; Longaker, Michael T. MD

doi: 10.1097/
Original Article

In fetal tissues, both soft and hard tissue healing (in long bones) have been found to be scarless. However, healing of membranous bone in the fetal craniofacial skeleton has not been well documented. Pregnant ewes (gestational age range, 80–95 days) underwent a hysterotomy, and fetal lambs had a full-thickness excision of the entire mandibular symphysis region (10 mm). Nonoperated controls were used for comparison (n = 8). After 10 days and 2 weeks, fetuses showed incomplete regeneration of the anterior mandible by examination, computed tomographic scan, and histology. By 4 weeks postoperatively, the mandibular defect had completely closed, but regenerated bony volume was less than control specimens. At 6 weeks postoperatively, the specimen demonstrated complete bony healing without scar or inflammation. Computed tomographic scan measurements for mandibular shape (length over width) was similar in experimental and control specimens. The data indicate that fetal lamb membranous bone defects heal in a scarless fashion and suggest preprogrammed migration of osteogenic tissue.

In a fetal lamb model, full-thickness mandibular symphysis excision resulted in complete scarless mandibular regeneration in utero within six weeks.

From the *Skull Base Institute, Cedars Sinai Medical Center, Los Angeles, CA; †Institute of Reconstructive Plastic Surgery, New York University Medical Center, New York, NY; ‡Division of Plastic and Reconstructive Surgery, University of California, Los Angeles, CA; §Laboratory of Developmental Biology and Repair, New York University Medical Center, New York, NY; ¶Department of Pathology & Laboratory Medicine, The New York Eye and Ear Infirmary, New York, NY; and ∥Department of Surgery, Stanford University School of Medicine, CA.

Received April 27, 2004 and accepted for publication, after revision, June 30, 2004.

Reprints: James P. Bradley, MD, Division of Plastic & Reconstructive Surgery, David Geffen School of Medicine, University of California, UCLA Medical Plaza, Suite 465, Los Angeles, CA 90095. (Tel): 310-794-7616; (fax): 310-206-6833; E-mail:

© 2005 Lippincott Williams & Wilkins, Inc.