Abstract
Ameloblastomas are benign, locally invasive odontogenic tumors that comprise approximately 1% of tumors within the jaws, with 66% located in the posterior mandible. If left untreated, these lesions can reach enormous size, resulting in considerable deformity and associated morbidity. Traditionally, defects >6 cm warranted a free-flap fibula transfer or iliac crest autogenous graft. Surgical treatment for the two presented cases included a large (>6 cm) mandibular segmental resection with immediate reconstruction via a tissue-engineering protocol that included bone morphogenetic protein (rhBMP-2), bone marrow aspirate concentrate, and cortical bone chips. Both patients had an uneventful postoperative course and healed satisfactorily. Established bone reconstruction determinants include bone volume, facial counter, esthetics, and restoration of functionality. Advances in tissue engineering provide a legitimate alternative while decreasing the risks, length of hospital stay, and postoperative morbidity.
Keywords: Bone marrow aspirate, bone morphogenetic protein, mandibular defects, tissue engineering
Ameloblastomas are locally invasive benign odontogenic tumors that can reach significant size and necessitate large resections. Autogenous corticocancellous grafts have been considered the reconstructive standard for defects >6 cm, to include the iliac crest as well as vascularized free-flap transfer grafts.1 However, these reconstructive techniques present a multitude of risks and adverse effects, including increased length of hospital stay, additional surgical sites, and the potential for increased morbidity.2–4 In contrast, tissue engineering not only improves surgical efficiency, but also decreases morbidity while maintaining desirable osteogenic properties.4,5 With the ultimate objective of restoring facial contour while providing a matrix for dental rehabilitation, tissue engineering has gained considerable interest as a legitimate treatment option.1 The following two cases provide an example of favorable outcomes using these techniques.
CASE PRESENTATIONS
Two patients presented to the Oral and Maxillofacial Surgery Clinic for evaluation. The patients’ history and symptoms at the time of presentation are summarized in Table 1. Clinical examination of Patient 1 revealed obvious extraoral asymmetry of the lower facial third. The intraoral, buccal, and lingual examination revealed firm expansion extended anteriorly to the parasymphysis region. Clinical examination of Patient 2 revealed intraoral firm expansion in a buccal and lingual dimension as well as an edentulous posterior left mandible due to bony expansion. Computed tomography (CT) was obtained in both cases, depicting expansive lesions of the right and left mandible, respectively (Table 1, Figure 1a–1b, Figure 2a–2c). In addition, virtual surgical planning was used to allow for the fabrication of a reconstruction plate and aid in surgical preparation.
Table 1.
Characteristics of two patients undergoing reconstruction of segmental mandibular defects via tissue engineering
| Variable | Patient 1 | Patient 2 |
|---|---|---|
| History | 62-year-old woman with excisional biopsy of ameloblastoma 8 years earlier | 24-year-old woman with no past medical history |
| Symptoms | Asymptomatic | Malocclusion, left mandibular paresthesia |
| Examination | Buccal and lingual firm expansion, extraoral expansion and asymmetry of lower face | Intraoral buccal and lingual expansion, edentulous posterior left mandible |
| Imaging dimensions | 6.0 × 5.0 × 3.7 cm | 4.4 × 2.1 × 2.1 cm |
| Virtual surgical planning | Yes | Yes |
| Reconstruction | Tissue engineering protocol, rib autograft, reconstruction plate | Tissue engineering protocol, cadaveric rib allograft, reconstruction plate |
| Nerve allograft | Yes | Yes |
Figure 1.
Patient 1. Preoperative (a) panoramic radiograph and (b) CT (coronal bone window), measuring 6.5 × 3.7 cm. (c) Postoperative panoramic radiograph at 4 months showing reconstruction plate (orange arrow), costochondral graft (blue arrow), and tissue-engineered bone allograft (green arrow).
Figure 2.
Patient 2. Preoperative (a) panoramic radiograph and (b, c) CT (axial and coronal bone window), measuring 4.2 × 2.1 × 2.1 cm. (d) Postoperative panoramic radiograph at 4 months showing reconstruction plate (orange arrow) and tissue-engineered bone allograft (green arrow).
Reconstruction was performed based on a tissue engineering protocol. Both patients were taken to the operative room for surgical resection and immediate reconstruction. A combined intraoral and extraoral approach was used to allow access in both cases. For Patient 1, the zygomatic arch was osteotomized to allow for unfettered access to the expansive lesion. Following anterior osteotomy in the parasymphysis region, disarticulation of the condyle easily aided in completing the hemimandibulectomy. A costochondral autograft was obtained from the patient’s right sixth rib to reconstruct the temporomandibular joint aspect. For Patient 2, the resection did not require disarticulation of the joint, and an osteotomy was performed at the anterior parasymphysis region and mid-ramus. A cadaveric rib allograft was secured to the inferior aspect of the reconstruction plate to provide for an inferior stop for bone grafting material. Nerve allografts were secured to the inferior alveolar nerve stumps and a multilayered water-tight closure concluded the procedure.
Both patients demonstrated expected surgically related swelling during the first week postoperatively, which progressively decreased. Postoperative imaging at 4 months demonstrated a well-adapted reconstruction plate with adequate bone volume (Figure 1c, Figure 2d).
All defects were accessed based on longitudinal length to determine required volumes based on the following: (1) corticocancellous bone chips, ratio of 10 cc per 1 cm defect; (2) 10 cc bone marrow aspirate, ratio of 10 cc per 1 cm defect, (3) large rhBMP-2 kit (8 cc) for defects >4 cm. Bone marrow was harvested via trochar and cannula from the anterior iliac crest with multidirectional aspirates and separated into individual vials for centrifuge. The cell rich portion was thoroughly mixed with the corticocancellous bone chips and morselized bone morphogenetic protein after proper constitution prior to placement.
DISCUSSION
Numerous articles in the past decade have demonstrated very promising results with the use of tissue engineering principles in lieu of more invasive reconstructive options. When evaluating patients from 2010 to 2014 with large mandibular defects restored with tissue engineering techniques, Melville found tissue engineering to have a 100% success rate. The defining parameters of success were determined by bony union, graft volume, and the allowance of dental implant placement.5,6 Similarly, from 2014 to 2019, the authors determined successful rehabilitation in 27 of 30 patients at the 5-year follow-up interval.7
The three desired principles of osteoconduction, osteoinduction, and osteogenesis are also fulfilled via tissue engineering methods. Osteoconduction provides a scaffold for bone cell migration. Osteoinduction is the principle of progenitor cells differentiating into osteoblastic cells for bone production. Osteogenesis quite literally means the formation of new bone.8,9 This ultimately provides for an adequate bone volume of natural bone generation for maxillofacial reconstruction.
As previously argued, the length of the defect may not necessarily dictate the restorative options. In a large study of 61 patients reconstructed with nonvascularized grafts, Marechek determined the success rates to be similar for osseous defects <6 cm and >6 cm, thus concluding that the size of the defect has little limiting power.10 Similarly, Schlieve demonstrated that nonvascularized bone grafts carry a very high success rate of 90%.11
The evolving science focusing on tissue engineering will continue to provide promising results, further confirming its potential role in restoring large osseous defects in the head and neck region. Tissue engineering techniques should continue to be explored as a proven alternative to autogenous grafting techniques.1 While the radiographs at an early follow-up period suggest success in terms of restorability, facial contour, and bone volume, there are limited data comparing osteomyocutaneous grafts and tissue-engineered bone grafting techniques.
References
- 1.Melville JC, Tran HQ, Bhatti AK, Manon V, Young S, Wong ME.. Is reconstruction of large mandibular defects using bioengineering materials effective? J Oral Maxillofac Surg. 2020;78(4):661.e1–661.e29. doi: 10.1016/j.joms.2019.11.024. [DOI] [PubMed] [Google Scholar]
- 2.Anthony JP, Rawnsley JD, Benhaim P, Ritter EF, Sadowsky SH, Singer MI.. Donor leg morbidity and function after fibula free flap mandible reconstruction. Plast Reconstr Surg. 1995;96(1):146–152. doi: 10.1097/00006534-199507000-00022. [DOI] [PubMed] [Google Scholar]
- 3.Marx RE, Morales MJ.. Morbidity from bone harvest in major jaw reconstruction: a randomized trial comparing the lateral anterior and posterior approaches to the ilium. J Oral Maxillofac Surg. 1988;46(3):196–203. doi: 10.1016/0278-2391(88)90083-3. [DOI] [PubMed] [Google Scholar]
- 4.Harris BN, Bewley AF.. Minimizing free flap donor-site morbidity. Curr Opin Otolaryngol Head Neck Surg. 2016;24(5):447–452. doi: 10.1097/MOO.0000000000000286. [DOI] [PubMed] [Google Scholar]
- 5.Hernigou P, Dubory A, Roubineau F, et al. Allografts supercharged with bone-marrow-derived mesenchymal stem cells possess equivalent osteogenic capacity to that of autograft: a study with long-term follow-ups of human biopsies. Int Orthop. 2017;41(1):127–132. doi: 10.1007/s00264-016-3263-7. [DOI] [PubMed] [Google Scholar]
- 6.Melville JC, Marx RE, Tursun R, et al. The utilization of allogeneic bone, bone morphogenetic protein and bone marrow aspirate concentrate for immediate reconstruction of benign tumor continuity defects. J Oral Maxillofac Surg. 2014;72(9):204–205. doi: 10.1016/j.joms.2014.06.367. [DOI] [Google Scholar]
- 7.Melville JC, Nassari NN, Hanna IA, Shum JW, Wong ME, Young S.. Immediate transoral allogeneic bone grafting for large mandibular defects: less morbidity, more bone. A paradigm in benign tumor mandibular reconstruction? J Oral Maxillofac Surg. 2017;75(4):828–838. doi: 10.1016/j.joms.2016.09.049. [DOI] [PubMed] [Google Scholar]
- 8.Herford AS, Boyne PJ.. Reconstruction of mandibular continuity defects with bone morphogenetic protein-2 (rhBMP-2). J Oral Maxillofac Surg. 2008;66(4):616–624. doi: 10.1016/j.joms.2007.11.021. [DOI] [PubMed] [Google Scholar]
- 9.Davies SD, Ochs MW.. Bone morphogenetic proteins in craniomaxillofacial surgery. Oral Maxillofac Surg Clin North Am. 2010;22(1):17–31. doi: 10.1016/j.coms.2009.10.007. [DOI] [PubMed] [Google Scholar]
- 10.Marechek A, AlShare A, Pack S, Demko C, Quereshy FA, Baur D.. Nonvascularized bone grafts for reconstruction of segmental mandibular defects: is length of graft a factor of success? J Oral Maxillofac Surg. 2019;77(12):2557–2566. doi: 10.1016/j.joms.2019.05.008. [DOI] [PubMed] [Google Scholar]
- 11.Schlieve T, Hull W, Miloro M, Kolokythas A.. Is immediate reconstruction of the mandible with nonvascularized bone graft following resection of benign pathology a viable treatment option? J Oral Maxillofac Surg. 2015;73(3):541–549. doi: 10.1016/j.joms.2014.10.019. [DOI] [PubMed] [Google Scholar]