Tissue-engineered bone for maxillary sinus augmentation

Tissue-engineered bone for maxillary sinus augmentation
June 2004
Ronald Schimming, MD, DMD, PhD*
Rainer Schmelzeisen, MD, DMD, PhDÇƒÜ
Journal of Oral and Maxillofacial Surgery Online
Abstract
Purpose Autologous, allogenic, and alloplastic materials for bony reconstruction in the craniomaxillofacial region have specific drawbacks stimulating the ongoing search for new materials. Cultivated skin and mucosa grafts are in clinical routine use in head and neck reconstruction but so far, to the best of our knowledge, no successful clinical application has been described of periosteum-derived tissue-engineered bone for augmentation of the edentulous posterior maxilla.
Patients and methods In a clinical study, augmentation of the posterior maxilla was carried out using a bone matrix derived from mandibular periosteum cells on an Ethisorb (Ethicon, Norderstedt, Germany) fleece. In this report, we show the fabrication of the matrix, clinical application, and results in 27 patients.
Results In 18 patients, an excellent clinical, radiologic, and histologic result could be proved 3 months after augmentation. Histologically, the bone biopsy samples from these patients revealed mineralized trabecular bone with remnants of the biomaterial. An unsuccessful result was found in 8 cases with a more extended augmentation procedure. The clinical inspection 3 months after augmentation showed almost no formation of new bone. In contrast, a replacement resorption with connective tissue was found. This may be the result of failure of the initial supply of the cells embedded within large cell-polymer constructs with sufficient oxygen and nutrients to sustain their survival and proliferation and allow for the integration of the developing tissue within the surrounding tissue.
Conclusion Our achieved results suggest that periosteum-derived osteoblasts on a suitable matrix can form lamellar bone within 3 months after transplantation and provide a reliable basis for simultaneous or secondary insertion of dental implants.
Bone augmentation procedures in oral and craniomaxillofacial surgery before implant insertion are most frequently carried out with autografts or allografts or composite material.1ÇƒÏ4 Independent of the location of the harvesting site, donor site morbidity must also be considered when using autologous grafts. There is only a limited amount of intraoral bone suitable for harvesting and grafting. Some other autologous graft sources are unsuitable for the reconstruction in implant cases owing to poor tissue quality and/or quantity and, possibly, the difficult sculpturing necessary.
Alloplastic materials in turn have drawbacks, particularly in a vascularly compromised environment.
Tissue-engineering procedures for bony augmentations of the maxilla offer significant advantages compared with conventional grafts, as there is minimal or no donor site morbidity. Ideally, these procedures are used under outpatient conditions under local anesthesia, using exclusively autologous material with bone-forming capacity.
Engineering procedures using living tissues in vivo require new concepts in cell culture technology. Compared with conventional cell cultures, the development of engineered tissues depends on a 3-dimensional arrangement of cells and the formation or synthesis of an appropriate extracellular matrix. Special emphasis must be given to the major role of the extracellular matrix and cell differentiation in an artificial tissue. New technical approaches of tissue engineering are compared with the natural development of tissues in vivo. Current methods using resorbable biomaterials, tissue encapsulation, and perfusion culture are discussed. Major consideration is given to scaffold structures of biomaterials that define a 3-dimensional shape of a tissue or guide matrix formation.5
In the field of tissue engineering of bony materials, naturally derived and synthetic polymers, composites, ceramics, and bone morphogenic protein, as well as cellular systems are being studied.5,6 In addition to investigations, in vivo tissue-engineering approaches for bone repair have been, up to now, limited to animal studies.7ÇƒÏ11 Fialkov et al11 described the development of a new method of poly(lactide-coglycolide) (PLGA) foam processing, enabling the production of a biodegradable scaffold with similar porosity to human trabecular bone. The scaffolds alone and loaded with bone marrow cells were implanted in critical-sized defects in rabbits with a significantly higher bone formation index for the cell-loaded scaffolds.11 Karp et al12 reported an experiment using a Wistar rat model and pure PLGA scaffolds loaded with rat bone marrow cells and fibrin.
Animal experiences strongly encourage the approach of transplantation within a suitable carrier structure for the reconstruction of critical-sized bone defects.11,13 Periosteum has been demonstrated to have cell populations, which include chondroprogenitor and osteoprogenitor cells, that can be isolated in tissue culture and form both cartilage and bone.
Tissue-engineered bone and cartilage repair using cultured periosteal cells was first described by Rich et al14 in 1994 and Breitbart et al13 in 1998 from the same working group. Breitbart et al used periosteal tissue isolated from the proximal tibiae of adult New Zealand White rabbits for cell cultures under osteogenic conditions. Together with a polyglycolic acid scaffold, the repair of critical-sized calvarial defects in a rabbit model was performed with good results.13 Rich et al14 reported that periosteal cells cultured under chondrogenic conditions and seeded into polymer scaffolds can be used to repair articular cartilage defects.
Preconditions for the clinical application described here were developed by Sittinger et al5 in 1996 and Perka et al15 in 2000. They reported the technique of segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits. On 12 New Zealand White rabbits, 8-mm metadiaphyseal ulna defects were created bilaterally and subsequently filled with cell-fibrin beads, with polymers seeded with cells, compared with controls with fibrin beads and polymers alone and untreated defects. The histologic and radiologic scoring was superior for both experimental groups. Control groups revealed only poor healing indices and untreated defects did not heal. The highest histologic score was noted in the group with polymer fleece containing periosteal cells.15
Based on these animal experiments and extensive discussion of possible clinical indications, a prospective clinical study with application of tissue-engineered bone transplants for augmentation of the maxilla (sinus lift) was initiated.
The study was approved by the local Ethics Committee of the University of Freiburg (ZERM).
Similar to this study and based on the same preclinical investigations at the Department for Orthopaedic Surgery and Traumatology (University of Freiburg), Ergelett et al16 used the arthroscopic implantation of tissue-engineered autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint.
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