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CASE REPORT

Mandible Augmentation for Osseointegrated


Implants Using Tissue Engineering Strategies
Ming-Huei Cheng, M.D.,
M.H.A.
Eric M. Brey, M.D.
Betul Gozel Ulusal, M.D.
Fu-Chan Wei, M.D.
Taipei, Taiwan; and Chicago, Ill.

D
esigning flaps that meet the specific func- cells, and bioactive proteins in the exact stoichi-
tional and geometric requirements of ometry found in mature bone.3
oromandibular defects often requires sig- In this study, we present a clinical case in
nificant amounts of donor tissue and complex which a similar procedure was used to fabricate
surgical procedures. In addition, the use of au- an osseous flap for augmenting mandible height
tologous tissue may be hindered by limited avail- during reconstruction. A molded polymethyl-
ability and the associated donor-site morbidity. methacrylate tissue chamber was used to explore
Extensive work is underway in the development the feasibility of using autogenous iliac mor-
of tissue-engineered substitutes, but clinical ap- cellized bone graft in a 58-year-old patient to
plication in the reconstruction of large defects engineer a bone flap. Further, the “take” and
remains a long-term goal.1 However, tissue- long-term durability of the engineered bone
engineering approaches can enhance current block were assessed after its transfer for mandi-
reconstructive procedures. Scaffold-guided tis- ble reconstruction and osseointegrated implant
sue regeneration is one of the key approaches to insertion.
tissue engineering.2– 4 This method involves seed-
ing porous, biodegradable matrices with donor CASE REPORT
cells (e.g., cultured osteoblasts or bone marrow A 58-year-old man with advanced buccal squamous cell car-
stromal cells) and/or growth factors (e.g., bone cinoma (T2N2M0) underwent wide tumor excision and right
morphogenetic proteins), and then implanting modified radical neck dissection in another hospital. The com-
posite defect, involving the right segmental mandible and a
the scaffolds to induce and direct the growth of through-and-through buccal defect, was reconstructed with a
new, healthy tissue. The ability to control scaf- pectoralis major myocutaneous flap and a reconstruction plate.
fold geometry could result in engineering tissues The surgical procedure was followed by 6000 cGy of radiother-
with the exact three-dimensional geometry of apy. Eleven months after the surgical procedure, he was re-
ferred to our clinic with severe trismus (interincisal distance: 0
the patient’s defect. cm) (Fig. 1). After removal of the reconstruction plate and
Experimental work in sheep has shown that bilateral release of the contracture in the buccal regions, triple
prefabricated chambers packed with morcellized flaps were planned to reconstruct the resultant defects. A free
bone graft and implanted adjacent to the osteo- anterolateral thigh cutaneous flap (12 ⫻ 6 cm) and a radial
genic surface of the periosteum yields three- forearm flap (5 ⫻ 2 cm) were used to resurface the right buccal
and commissure and left buccal defects, respectively; a free
dimensional bone flaps.2– 4 Durable and transfer- fibula flap was used to reconstruct the mandible. Complete
able vascularized tissue units of defined shapes healing with satisfactory mouth opening was attained, and the
could be fabricated. Morcellized bone graft was patient demanded teeth after a follow-up period of 1 year.
used because it can be considered the ideal bio- However, despite solid union of the vascularized fibula flap with
the mandible, the height was inadequate, at 5 mm high and 50
material for bone formation, as it provides a mm long, for further dental rehabilitation (Fig. 2). Additional
degradable scaffold of matrix proteins, viable reconstruction with free flaps was hampered due to difficulty
finding an adequate recipient vessel because of the three pre-
From the Department of Plastic and Reconstructive Surgery, vious free flaps. In addition, the patient refused another major
Chang Gung Memorial Hospital, and Department of Bio- operation. The case was therefore considered for reconstruc-
medical Engineering, Illinois Institute of Technology. tion with a three-dimensional scaffold-guided bone flap.
Received for publication October 28, 2004; accepted March Preformed hollow rectangular chambers were fabricated
17, 2005. from dental-grade polymethylmethacrylate, as described
previously.4 Briefly, the chambers were enclosed on five sides
Copyright ©2006 by the American Society of Plastic Surgeons
and open on one side, with inner dimensions of 1 ⫻ 1 ⫻ 5 cm
DOI: 10.1097/01.prs.0000221120.11128.1a (Fig. 3). The three-dimensional shape of this chamber was

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Plastic and Reconstructive Surgery • July 2006

Fig. 3. Hollow rectangular chambers were fabricated from dental-


grade polymethylmethacrylate that was enclosed on five sides and
open on one side, with inner dimensions of 1 ⫻ 1 ⫻ 5 cm.

the right iliac crest and packed into the polymethylmethacrylate


chamber. After the chamber was packed with morcellized bone
graft, the polyethylene cuff was sutured to the periosteum with
its open side exposed to the osteogenic surface of the perios-
teum to create an enclosed space. After 8 weeks of implantation,
solid bone was found in the polymethylmethacrylate chamber
extending from the periosteum. The chamber implantation
time was based on extensive animal studies that determined that
maximum bone graft formation occurs at 8 weeks after
implantation.4 The engineered bone graft, along with the peri-
osteum, was harvested and transferred to augment the mandi-
ble height. The native mandibular bone was burred slightly to
Fig. 1. Interincisal distance of the patient was 0 cm 11 months allow good bone contact for vascular connections. Donor iliac
periosteum was sutured to the recipient mandibular perios-
after the initial ablative surgery and radiotherapy for buccal
teum to allow a rapid establishment of blood supply to the bone.
tumor. At a 1-year follow-up, the engineered bone remained viable
(Fig. 4) and the bone height had increased up to 5 mm (Fig.
5). Three osseointegrated dental implants, 4 mm in diameter
designed to achieve the optimal height for osseointegrated and 10 mm in height, were inserted into the engineered bone.
teeth implantation. A 7-mm polyethylene cuff was bonded with Implants were fixed firmly. The histologic samples revealed
medical-grade silicone adhesive around the perimeter of the adequately regenerated compact bone with numerous haver-
open side, to allow suture fixation in vivo. The chamber was sian systems and mature osteocytes (Fig. 6). Unfortunately, the
placed in a 100°C water bath after fabrication to remove re- patient died due to hepatocellular carcinoma before placement
sidual monomer and volatile residues. The chamber was ster- of the dental implants. However, the most recent examination
ilized in ethylene oxide gas. at 16 months revealed well-retained osseointegrated implants in
A total of 5 cc of cancellous bone graft was harvested from the engineered bone (Figs. 7 and 8).

Fig. 2. Radiologic view of the neomandible, demonstrating inadequate height 1


year after reconstruction with the vascularized fibula flap.

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Volume 118, Number 1 • Mandible Augmentation

Fig. 4. Perioperative view of the viable engineered bone 1 year


after implantation.
Fig. 6. Histological appearance of the engineered bone exhib-
iting a compact bone configuration with mature osteocytes and
DISCUSSION
numerous haversian canals (hematoxylin and eosin, ⫻100).
Tissue engineering is a multidisciplinary/in-
terdisciplinary field that integrates the principles
of biology and engineering to develop tissue sub-
stitutes to restore, maintain, or improve the func-
tion of diseased or damaged human tissues.5 It is
a broad field that includes the patient’s own body
to regenerate damaged tissues or replacing the
patient’s cells or organs with living tissue grown in
vitro to functionally replace living organs or tis-
sues. Tissue engineering was initially defined as a
field in the late 1980s and is now well established
and progressing rapidly. In this unique case, iliac
bone graft was used to guide generation of a bone
flap of a defined three-dimensional geometry that
was successfully transferred to a recipient site. This Fig. 7. Well-retained implants 4 months after implantation into
approach was based on tissue-engineering studies the engineered bone.
in which the patient’s own regenerative capacity
was manipulated to grow a segment of vascularized
bone with a predetermined geometry using min- trition. Adult bones are surrounded by perios-
imal donor tissue. teum that assists in new bone formation and neo-
The most critical aspects of successful transfer vascularization through its population of
of a tissue flap in vivo are blood supply and nu- progenitor cells and rich plexus of vessels located

Fig. 5. Radiologic view of the engineered bone (arrows) with an approximate


thickness of 5 mm.
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Plastic and Reconstructive Surgery • July 2006

bone graft has not been used clinically, this case


provides an example of how tissue-engineering
approaches can be used to improve current clin-
ical protocols. Of course, many studies are war-
ranted before routine clinical application will be
possible. A waiting period of 8 weeks may create a
potential disadvantage, and more clinical research
is required to develop methods for improving the
quality of the engineered bone. Since the engi-
neered bone units are presumed to be well
vascularized,3 future studies may explore the po-
tential feasibility of harvesting them as vascular-
ized flaps.
Ming-Huei Cheng, M.D., M.H.A.
Department of Plastic and Reconstructive Surgery
Fig. 8. Four-month postoperative view. Chang Gung Memorial Hospital
5, Fu-Hsin Street, Kwei-Shan
Tao–Yuan 333, Taiwan
micro.cheng@msa.hinet.net
in the inner (cambium) layer.6 Periosteum can minghueicheng@hotmail.com
form new bone after it has been stripped from
mature bone as long as its vascular supply remains
intact.7 In this study, the periosteum was chosen to REFERENCES
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2. Miller, M. J., Goldberg, D., Yasko, A., et al. Guided bone
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periosteum of the vascularized fibula, bone flap Tissue Eng. 2: 51, 1996.
take was facilitated. This procedure leads to an 3. Thomson, R. C., Mikos, A. G., Beahm, E., et al. Guided tissue
increase in thickness (1 mm to 5 mm). Although fabrication from periosteum using preformed biodegradable
histologic analysis indicated that the osteocyte polymer scaffolds. Biomaterials 20: 2007, 1999.
4. Cheng, M. H., Brey, E. M., Allori, A., et al. Ovine model for
number was less than that in mature compact engineering bone segments. Tissue Eng. 1/2: 214, 2005.
bone, at the long-term follow-up (16 months), 5. Liu, W., Cui, L., and Cao, Y. A closer view of tissue engineering
implants were well retained, with no loosening or in China: The experience of tissue construction in immuno-
bone resorption around the implants. competent animals. Tissue Eng. 9 (Suppl. 1): S17, 2003.
This is a preliminary study of successful man- 6. Whiteside, L. A., Ogata, K., Lesker, P., et al. The effects of
extraperiosteal and subperiosteal dissection: II. On fracture
dible augmentation with a bone graft fabricated healing. J. Bone Joint Surg. (Am.) 60: 26, 1978.
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