Os estudos abordando a regeneração dos tecidos dentários ganharam uma nova perspectiva com a utilização das células-tronco. E novas perspectivas têm surgido com a bioengenharia tecidual e as terapias periodontais e pulpares regeneradoras. O objetivo deste trabalho foi desenvolver o modelo experimental de autotransplante em ratos visando compará-lo à técnica de reimplante e estudar a capacidade terapêutica das células da medula óssea em diferentes biomateriais utilizados como matriz para a terapia de células-tronco no reparo dos tecidos dentais. Foram utilizados 23 ratos Wistar divididos em grupos de 1, 3, 15 e 60 dias para as técnicas de reimplante e autotransplante. Os grupos com injeção de células-tronco (CT) foram: (1) grupo de 3 dias, combinado à técnica de reimplante; (2) grupo de 15 dias com ambas as técnicas. Blocos contendo os três dentes molares superiores de cada lado dos ratos foram removidos, feitas radiografias periapicais e as peças foram processadas para inclusão em parafina. Foram avaliadas a espessura do ligamento periodontal (LPD) comparada entre os diferentes grupos e a morfologia celular e matriz extracelular relacionadas à superfície radicular, ao osso alveolar e à porção média do LPD, além das células da polpa dental de cada grupo. As células isoladas a partir da medula-óssea foram incubadas por 24h, 48h, e 72h em placas de cultura contendo membranas de colágeno bovino tipo I - CollaTape (Integra LifeSciences Corporation, Plainsboro, NJ, USA), enxerto ósseo - Extra Graft XG-13 (Silvestre Labs Quimica e Farmaceutica LTDA, RJ, Brazil) ou um dente molar de rato. Os espécimes foram observados em um microscópio invertido para contagem de células e processadas para observação no microscópio eletrônico de varredura (MEV). Os grupos de 1 e 3 dias apresentaram medidas de LPD significativamente maiores para a técnica de autotransplante quando comparadas ao reimplante. O grupo de 3 dias com CT não apresentou alterações pulpares significativas, diferente do controle (sem CT) O grupo de 15 dias com CT apresentou as mesmas características histológicas do grupo sem injeção de CT. A observação ao MEV dos biomateriais revelou que as células apresentaram pouca adesão e proliferação no enxerto ósseo e no cemento dentário quando comparados à membrana colágena. A técnica de reimplante associada à injeção de células-tronco sugere alguma influência da terapia com as células-tronco sobre a polpa. As distâncias aumentadas no LPD com a técnica de autotransplante podem não influenciar tanto o sucesso da técnica. As células mesenquimais da medula óssea possuem grande potencial para colonizarem a membrana colágena CollaTape que mostrou vantagens sobre o enxerto ósseo Extra Graft XG-13 como biomaterial para a aderência e a proliferação de células mononucleares da medula óssea, permitindo a diferenciação destas células. / The studies on the regeneration of dental tissues have gained a new perspective with the use of stem cells. And new perspectives have appeared with bioengineering and pulp and periodontal regenerative therapies. The aim of this study was to develop an experimental model of autotransplantation in rats in order to compare it with tooth reimplant technique and to study the therapeutic potential of bone marrow cells in different biomaterials used as scaffolds for stem cell therapy to repair dental tissues. 23 rats divided in 1, 3, 15 and 60 days groups were used for the techniques of tooth reimplant and autotranplant. The groups with stem cell injection (CT) were: (1) 3 days, combined with tooth replant technique; (2) 15 days with both techniques. Blocks containing the three molar teeth from each side of the rats superior jaws were removed, periapical radiographs were taken and the specimens were processed and embedded in paraffin. LPD thickness among different groups and cell morphology and extracellular matrix related to the root surface, alveolar bone and the middle portion of the LPD, and dental pulp cells were evaluated and compared from each group. Cells isolated from bone marrow were incubated for 24h, 48h and 72h in culture plates containing membranes of bovine collagen type I - CollaTape (Integra LifeSciences Corporation, Plainsboro, NJ, USA), bone graft - Extra Graft XG-13 (Silvestre Labs Chemical and Pharmaceutical Ltda, RJ, Brazil) or a mouse molar tooth. The specimens were observed using an inverted microscope for cell count and processed for observation in a scanning electron microscope (SEM). Groups 1 and 3 days showed LPD thickness significantly higher for tooth autotransplant technique when compared to reimplant. The group of 3 days with stem cells showed no significant pulp changes different from control (without stem cells). Group of 15 days with stem cells showed the same histological characteristics of the group without injection of stem cells. The biomaterials observation at SEM revealed that cells in the bone graft and in tooth cementum showed poor adhesion and prolifetarion when compared to collagen membrane The tooth reimplant technique associated with injection of stem cells suggests some influence of stem cells therapy on the pulp. The increased distances in LPD with tooth autotranplant technique may not influence the success of the technique. The bone marrow mesenchymal cells have great potential to colonize the collagen membrane CollaTape that showed advantages over bone graft Extra Graft XG-13 as a biomaterial for adhesion and proliferation of bone marrow mononuclear cells, allowing the differentiation of these cells.

Aim: The aim of this literature study was to systematically review the scientific evidence on the most effective donor sites and/or bone substitute material for secondary alveolar cleft grafting in alveolar cleft patients. Material and method: In order to acquire a systematic and transparent reporting this literature review was conducted according to the PRISMA statement. The literature search was performed in the following four databases; PubMed, CENTRAL, Web of Science and Scopus.The quality of the included studies was assessed using the revised Cochrane Risk of Bias 2 tool (RoB 2 tool). Result: The search identified 4754 studies. Five RCT studies was included in this systematic review and assessed different donor site or bone substitute materials. Two studies showed low risk of bias and three moderate risk of bias. Only one study showed a statistically significant difference when comparing iliac bone to substitute material however all studies presented substitute materials with satisfactory results. Conclusion: According to the data from this systematic review no clear conclusion can be drawn regarding what the most effective bone donor site and/or tissue engineered bone substitute material to use in secondary bone grafts. Based on the available evidence iliac bone could still be regarded as a benchmark, but more research and RCT’s of high quality are required, especially for artificial bone substitute materials. / Syfte: Syftet med denna litteraturstudie var att systematiskt granska den vetenskapliga evidensen gällande det mest effektiva bentagningsstället och/eller bensubstitutmaterialet vid sekundär bentransplantation hos patienter med käkspalt. Material och metod: För att uppnå en systematisk och transparent rapportering av denna litteraturstudie följdes PRISMA statement. Litteratursökningen gjordes i följande fyra databaser; PubMed, CENTRAL, Web of Science och Scopus. Kvaliteten av inkluderade studier granskades med hjälp av Cochrane Risk of Bias 2 tool (Rob 2 tool). Resultat: Sökningen identifierade 4754 studier. Fem RCT studier inkluderades i denna systematiska översikt vilka värderade olika bentagningsställen eller bensubstitut. Två studier bedömdes ha låg risk för bias och tre artiklar måttlig risk för bias. Endast en studie visade på en statistiskt signifikant skillnad vid jämförelse av höftben med bensubstitut däremot presenterade samtliga studier substitutmaterial med tillfredsställande resultat. Konklusion: Denna systematiska översikt visade att ingen klar slutsats kan dras gällande vilken det mest effektiva bentagningsstället eller bensubstitutsmaterialet är för sekundär bentransplantation hos patienter med käkspalt. Baserat på tillgänglig evidens kan transplantat från höftbenet fortfarande anses vara bäst lämpat men mer forskning samt RCT studier av hög kvalité erfordras, särskilt för artificiella bensubstitutmaterial.

Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics.

Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics.