Case Report: Reconstruction of a Large Maxillary Defect With an Engineered, Vascularized, Prefabricated Bone Graft

Abstract

The reconstruction of complex midface defects is a challenging clinical scenario considering the high anatomical, functional, and aesthetic requirements. In this study, we proposed a surgical treatment to achieve improved oral rehabilitation and anatomical and functional reconstruction of a complex defect of the maxilla with a vascularized, engineered composite graft. The patient was a 39-year-old female, postoperative after left hemimaxillectomy for ameloblastic carcinoma in 2010 and tumor-free at the 5-year oncological follow-up. The left hemimaxillary defect was restored in a two-step approach. First, a composite graft was ectopically engineered using autologous stromal vascular fraction (SVF) cells seeded on an allogenic devitalized bone matrix. The resulting construct was further loaded with bone morphogenic protein-2 (BMP-2), wrapped within the latissimus dorsi muscle, and pedicled with an arteriovenous (AV) bundle. Subsequently, the prefabricated graft was orthotopically transferred into the defect site and revascularized through microvascular surgical techniques. The prefabricated graft contained vascularized bone tissue embedded within muscular tissue. Despite unexpected resorption, its orthotopic transfer enabled restoration of the orbital floor, separation of the oral and nasal cavities, and midface symmetry and allowed the patient to return to normal diet as well as to restore normal speech and swallowing function. These results remained stable for the entire follow-up period of 2 years. This clinical case demonstrates the safety and the feasibility of composite graft engineering for the treatment of complex maxillary defects. As compared to the current gold standard of autologous tissue transfer, this patient’s benefits included decreased donor site morbidity and improved oral rehabilitation. Bone resorption of the construct at the ectopic prefabrication site still needs to be further addressed to preserve the designed graft size and shape.

A BMP-2–triggered in vivo osteo-organoid for cell therapy

“…It can also be used as a source of bone graft. A recent case report confirmed the clinical translation capacity of in vivo osteo-organoid strategy in addressing large maxillary defect ( 24 ). We have previously confirmed that the bone morphogenetic protein–2 (BMP-2)–loaded scaffold–induced in vivo osteo-organoid at different developmental stages could serve as a robust osteogenic tissue for critical bone defect repair ( 25 , 26 ).…”

Bioactive Scaffolds as a Promising Alternative for Enhancing Critical-Size Bone Defect Regeneration in the Craniomaxillofacial Region

“…Bone from allogeneic donors is gamma irradiated or freeze-dried to eliminate the cellular components and pathogenic agents, thus reducing their immunogenicity. 14 Allografts are osteoconductive and retain at least partly their osteoinductivity depending on the decellularization process. Although allografts are also histocompatible, they exhibit a higher failure rate compared to autografts.…”

“…Bone tissue from living or cadaveric human donors constitutes the allografts. Bone from allogeneic donors is gamma irradiated or freeze-dried to eliminate the cellular components and pathogenic agents, thus reducing their immunogenicity . Allografts are osteoconductive and retain at least partly their osteoinductivity depending on the decellularization process.…”

“…InFuse bone graft, which consists of a Col type I sponge laden with rhBMP-2, was first approved by the FDA in 2002 for application in lumbar interbody fusion in skeletally mature individuals and later, in 2007 was approved to perform augmentation of alveolar ridges in extraction sockets and elevation of the maxillary sinus floor. 31 Since then, rhBMP-2 has also been used for off-label applications, such as for treating maxillary clefts 112 and maxillary large bone defects caused by tumor resections, 14 and in mandibular CSDs created by the removal of tumors, 32 osteomyelitis, or osteonecrosis 113 (Figure 4I), suggesting its effectiveness in inducing CSD regeneration in the CMF region. 112 However, other studies that have reviewed the outcomes of rhBMP-2 in craniofacial applications indicate a need for more evidence of its efficacy for maxillary sinus floor augmentation, calvarial and mandibular reconstruction, and distraction osteogenesis.…”

Current Trends in the Reconstruction and Rehabilitation of Jaw following Ablative Surgery

“…The ability to regenerate bone gives the surgeon another avenue to reconstruct the patient to normalcy without donor site morbidity [ 70 ]. To address instances where the soft tissue condition is suboptimal or a soft tissue defect is present after the excision of a malignant tumor, a combination of tissue-engineered bone with radial forearm flap and latissimus dorsi flap has been reported by Schlund et al [ 71 ] and Ismail et al [ 77 ], respectively. ( Figure 3 ) Soft tissue engineering was also applied to fabricate keratinized oral mucosal grafts which were pre-laminated to a fibula flap for later jaw reconstruction [ 78 ].…”