Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4-loaded hydrogel directs hard tissue bioengineering.

Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering.

Regeneração óssea completa da maxila com atrofia severa utilizando telas de titânio e rhBMP-2 / Complete bone regeneration of severely atrophic maxilla using titanium meshes and rhBMP-2 ­ a case report

Diversas técnicas já foram propostas para viabilizar a reabilitação de pacientes com atrofias severas de maxila, como instalação de implantes zigomáticos, regenerações ósseas utilizando enxertos autógenos com áreas doadoras extrabucais, como osso ilíaco e calota craniana, dentre outras. Porém, todas estas técnicas possuem limitações, baixa previsibilidade e, algumas, grande morbidade para o paciente. Atualmente, alguns trabalhos têm mostrado bons resultados com o uso da técnica de ROG em atrofi as severas de maxila, utilizando telas de titânio associadas ao levantamento de seio maxilar bilateral, empregando como material substituto ósseo a rhBMP-2 (proteína óssea morfogenética humana do tipo 2). Com esta técnica, evita-se a utilização do osso autógeno e suas possíveis complicações, além do fato da rhBMP-2 ser o único biomaterial, além do osso autógeno, com características de osteoindução. O objetivo deste trabalho foi relatar um caso de paciente com atrofia severa de maxila submetida à técnica de ROG com tela de titânio e levantamento de seio maxilar bilateral, utilizando como material de enxertia a rhBMP-2 associada ao material heterógeno inorgânico. Após o período de neoformação óssea, a paciente foi submetida à cirurgia para instalação de sete implantes osseointegráveis convencionais e reabilitada com uma prótese total maxilar do tipo protocolo.

Several techniques have been proposed to rehabilitate patients with severely atrophic maxillae, such as the placement of zygomatic implants, bone regeneration using autogenous grafts with extraoral donor sites from the pelvic bone and skull cap, among others. However, all these techniques have limitations, low predictability and some contribute to high patient morbidity. Currently, some studies have shown positive results regarding the use of the GBR technique for severely atrophic maxilla using titanium meshes associated with bilateral maxillary sinus elevation using rhBMP-2 (recombinant human bone morphogenetic protein-2) as a bone substitute material. This technique does not require the use of autogenous bone and rhBMP-2 is the only bone substitute, which has osteoinduction characteristics. The aim of this study is to report a case of a patient with severely atrophic maxilla submitted to the GBR technique with titanium mesh and bilateral maxillary sinus elevation using rhBMP-2 as the grafting material associated with heterogeneous inorganic material. After new bone formation, the patient underwent surgery for the placement of 7 conventional osseointegrated implants and was rehabilitated with a implantretained maxillary prosthesis.

Histological analysis and gene expression profile following augmentation of the anterior maxilla using rhBMP-2/ACS versus autogenous bone graft.

AIM: The objective of this report was to present histological characteristics and gene expression profile of newly formed bone following horizontal augmentation of the atrophic anterior maxilla using recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) versus an autogenous bone graft (ABG). METHODS: Bone core biopsies from 24 subjects participating in a randomized clinical trial were obtained at dental implant placement, 6 months following alveolar ridge augmentation using rhBMP-2/ACS (rhBMP-2 at 1.5 mg/ml; total dose 4.2 mg) or a particulate ABG harvested from the mandibular retro-molar region. A titanium mesh was used to provide wound stability and space for bone formation. Analysis included histological/histometric observations and gene expression profile of the newly formed bone. RESULTS: rhBMP-2/ACS yielded bone marrow rich in capillaries, undifferentiated cells and bone lining cells compared with the ABG (p = 0.002). Whereas no significant differences were observed in total bone fraction (p = 0.53), non-vital bone particles trapped in lamellar vital bone were observed in the ABG group (p < 0.001). Real-time PCR showed greater BMP-2 and RUNX2 expression for rhBMP-2/ACS over the ABG (p = 0.001 and 0.0021, respectively), while the ABG exhibited greater expression of RANKL:OPG, BSP and OPN over rhBMP-2/ACS (p = 0.01, 0.005 and 0.0009, respectively). CONCLUSIONS: Our observations suggest that formative biological processes explain bone formation following implantation of rhBMP-2/ACS, whereas remodelling, resorptive/formative processes, characterizes sites receiving ABGs.

Effect of maxillary alveolar reconstruction on nasal symmetry of cleft lip and palate patients: a study comparing iliac crest bone graft and recombinant human bone morphogenetic protein-2.

BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 has been used in some craniofacial centers worldwide. However, its influence on nasal morphology is unknown. Thus, the objective of this investigation was to assess the effect of maxillary alveolar reconstruction on nasal position and symmetry in unilateral complete cleft lip patients who underwent traditional iliac crest bone grafting transferring versus reconstruction using rhBMP-2. METHODS: Nineteen unilateral complete cleft lip patients were randomly divided into two groups. In group 1, patients underwent traditional iliac crest bone grafting transferring (n = 11) and in group 2, patients underwent alveolar reconstruction using collagen matrix with lyophilized rhBMP-2 (n = 8). Computerized tomography (CT) imaging was performed preoperatively and at 6 months postoperatively using a previously standardized protocol. Linear distances using anatomic landmarks were performed using tridimensional CT data reformatted by the OsiriX(®) software. Quantitative and qualitative measurements to assess intra- and inter-group nasal position modifications were performed. RESULTS: Intra-group pre- and postoperative comparisons showed significant differences (p < 0.05) in two linear measurements of group 1, while group 2 did not present a difference (p > 0.05). Group 2 presented significant postoperative enhancement (p < 0.05) in the quantitative nasal symmetry in one measurement. Qualitative analysis showed postoperative nasal symmetry enhancement in 75% of the measurements of group 2 and 36% of group 1. There was no statistically significant difference in the inter-group comparisons. CONCLUSIONS: Our study demonstrated that both groups showed similar effect on nasal symmetry.

Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP-2/ACS or autogenous bone grafts: a proof-of-concept randomized clinical trial.

AIM: To compare the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) with autogenous bone graft for augmentation of the edentulous atrophic anterior maxilla. METHODS: Twenty-four subjects were enrolled in a randomized, controlled, parallel-group, open-label clinical trial. Subjects either received rhBMP-2/ACS (1.5 mg/ml) or particulated autogenous bone harvested from the mandibular retromolar region. A titanium-mesh was used to provide space and wound stability. A guide was used to standardize clinical recordings using an analogue caliper. Alveolar ridge width was also assessed using cone-beam computed tomography. RESULTS: rhBMP-2/ACS yielded significantly greater radiographic horizontal bone gain compared with autogenous bone graft at immediate subcrestal levels (1.5 ± 0.7 versus 0.5 ± 0.9 mm; p = 0.01); non-significant differences were observed at mid- (2.9 ± 0.8 versus 2.9 ± 0.9 mm; p = 0.98) and apical (1.7 ± 0.9 versus 1.8 ± 1.1 mm; p = 0.85) crestal levels. No significant differences in clinical horizontal bone gain were observed at 6 months between rhBMP-2/ACS and autogenous bone graft (3.2 ± 0.9 mm versus 3.7 ± 1.4 mm; p = 0.31). Sixty-two implants were placed after 6 month of healing with no significant differences between groups for number of implants, implant size, primary stability and survival. CONCLUSIONS: rhBMP-2/ACS appears a realistic alternative for augmentation of the edentulous atrophic anterior maxilla.