Abstract This study aimed to evaluate the osteogenic potential of hydroxyapatite (HA), Alginate (Alg), and Gelatine (Gel) composite in a critical-size defect model in rats. Twenty-four male rats were divided into three groups: a negative control with no treatment (Control group), a positive control treated with deproteinized bovine bone mineral (DBBM group), and the experimental group treated with the new HA-Alg-Gel composite (HA-Alg-Gel group). A critical size defect (8.5mm) was made in the rat's calvaria, and the bone formation was evaluated by in vivo microcomputed tomography analysis (µCT) after 1, 15, 45, and 90 days. After 90 days, the animals were euthanized and histological and histomorphometric analyses were performed. A higher proportion of mineralized tissue/biomaterial was observed in the DBBM group when compared to the HA-Alg-Gel and Control groups in the µCT analysis during all analysis periods. However, no differences were observed in the mineralized tissue/biomaterial proportion observed on day 1 (immediate postoperative) in comparison to later periods of analysis in all groups. In the histomorphometric analysis, the HA-Alg-Gel and Control groups showed higher bone formation than the DBBM group. Moreover, in histological analysis, five samples of the HA-Alg-Gal group exhibited formed bone spicules adjacent to the graft granules against only two of eight samples in the DBBM group. Both graft materials ensured the maintenance of defect bone thickness, while a tissue thickness reduction was observed in the control group. In conclusion, this study demonstrated the osteoconductive potential of HA-Alg-Gel bone graft by supporting new bone formation around its particles. HA, HA , (HA) Alg, Alg (Alg) Gel (Gel criticalsize Twentyfour Twenty four group, group) HAAlgGel . 8.5mm 85mm mm 8 5mm (8.5mm rat s calvaria (µCT 15 45 9 days performed tissuebiomaterial biomaterial However immediate postoperative Moreover HAAlgGal Gal conclusion particles (HA (Alg 4

Resumo Este estudo teve como objetivo avaliar o potencial osteogênico de um compósito de hidroxiapatita (HA), alginato (Alg) e gelatina (Gel) em um modelo de defeito de tamanho crítico em ratos. Vinte e quatro ratos machos foram divididos em três grupos: um controle negativo sem tratamento (grupo controle), um controle positivo tratado com osso bovino desproteinizado (grupo DBBM) e o grupo experimental tratado com o novo compósito HA-Alg-Gel (grupo HA-Alg-Gel). Um defeito de tamanho crítico (8,5mm) foi feito na calvária dos ratos, e a formação óssea foi avaliada por análise de microtomografia computadorizada in vivo (µCT) após 1, 15, 45 e 90 dias. Após 90 dias, os animais foram eutanasiados e análises histológicas e histomorfométricas foram realizadas. Uma maior proporção de tecido mineralizado/biomaterial foi observada no grupo DBBM quando comparado aos grupos HA-Alg-Gel e controle na análise de µCT durante todos os períodos de análise. Entretanto, não foram observadas diferenças na proporção tecido mineralizado/biomaterial no dia 1 (pós-operatório imediato) em relação aos períodos posteriores de análise em todos os grupos. Na análise histomorfométrica, os grupos HA-Alg-Gel e controle apresentaram maior formação óssea do que o grupo DBBM. Além disso, na análise histológica, cinco amostras do grupo HA-Alg-Gal exibiram espículas ósseas formadas adjacentes aos grânulos do enxerto contra apenas duas das oito amostras do grupo DBBM. Ambos os materiais de enxerto garantiram a manutenção da espessura óssea do defeito, enquanto uma redução da espessura do tecido foi observada no grupo controle. Em conclusão, este estudo demonstrou o potencial osteocondutor do enxerto ósseo de HA-Alg-Gel, promovendo a formação de osso novo ao redor das suas partículas. HA, HA , (HA) Alg (Alg Gel (Gel controle, controle) HAAlgGel HAAlgGel. . HA-Alg-Gel) 8,5mm 85mm mm 8 5mm (8,5mm (µCT 15 4 9 dias realizadas mineralizadobiomaterial mineralizado biomaterial Entretanto pósoperatório pós operatório imediato histomorfométrica disso histológica HAAlgGal Gal conclusão HAAlgGel, Gel, partículas (HA

ABSTRACT Purpose: to evaluate biocompatibility and osteogenic potential of hydroxyapatite/alginate composite after its implantation on rat calvarian critical bone defect. Methods: thirty adults male Wistar rats were randomly distributed into two groups: GHA – critical bone defect filled with hydroxyapatite/alginate composite granules (HA/Alg) and CG – critical bone defect without biomaterial; evaluated at biological points of 15, 45 and 120 days. Results: the histomorphometrically analyses for GHA showed osteoid matrix deposition (OM) among the granules and towards the center of the defect in centripetal direction throughout the study, with evident new bone formation at 120 days, resulting in filling 4/5 of the initial bone defect. For CG, this finding was restricted to the edges of the bone margins and formation of connective tissue on the residual area was found in all biological points. Inflammatory response on GHA was chronic granulomatous type, discrete and regressive for all biological points. Throughout the study, the CG presented mononuclear inflammatory infiltrate diffuse and regressive. Histomorphometry analyses showed that OM percentage was evident for GHA group when compared to CG group in all analyzed periods (p > 0.05). Conclusions: the biomaterial evaluated at this study showed to be biocompatible, bioactive, osteoconductive and biodegradable synchronously with bone formation. Purpose hydroxyapatitealginate hydroxyapatite alginate Methods groups HA/Alg HAAlg HA Alg (HA/Alg 15 4 12 days Results (OM 5 4/ type p 0.05. 005 0.05 . 0 05 0.05) Conclusions biocompatible bioactive 1 00 0.0 0.

Abstract The objective was to evaluate the effect of oral administration of strontium (Sr) on the regeneration of a critical bone defect. Twenty Wistar rats were divided into two groups, assessed at 15 and 60 days postoperatively: GSr - oral administration of Sr; and CG - without oral administration of Sr. At 15 and 60 days, blood was collected to measure Sr and calcium (Ca), and the calvaria was removed for histomorphological and histomorphometric analyses. Sr+2 plasmatic concentrations were higher in GSr than in CG. The dosage of Ca+2 showed a small increase in the CG about the GSr. In all evaluated groups, new bone formation was restricted to the edges of the defect, and the residual area was filled with fibrous connective tissue. The oral administration of Sr associated with HA microspheres substituted by the metal, in a concentration of 23 mol%, did not affect the formation of the osteoid matrix. (Sr defect groups 1 6 postoperatively Ca, Ca , (Ca) analyses Sr2 2 Sr+ Ca2 Ca+ tissue metal mol mol% matrix (Ca

ABSTRACT Purpose To analyze the investments of the Unified Health System in Brazil destined to vocology. Methods Ecological, quantitative study with public, secondary data, available on the DataSUS/TABNet digital platform. The data refer to the quantity and values of the vocology procedures, presented and approved during the period from 2008 to 2021 in Brazil. After data collection and descriptive analysis, absolute and relative values, growth rates and deficit were adopted. Results In the analyzed period, 4,6 million procedures were carried out at a total cost of R$18,350 million. Of these, 2,4 million procedures were approved to be paid by state and municipal health departments at a total cost of R$10,617 million to public coffers. These transferred values represented a growth rate in investments destined to vocology procedures of up to 491%, if compared to 2008, however, a financial deficit rate of up to 360% was accumulated throughout the studied period. Conclusion It was verified that the public investments destined to vocology had a significant growth in all the indices analyzed, despite not having been passed on the totality of the values referring to the procedures carried out. Ecological DataSUSTABNet DataSUS TABNet platform 200 202 analysis adopted 46 4 6 4, R18350 R 18 350 R$18,35 these 24 2 2, R10617 10 617 R$10,61 coffers 491 491% however 360 20 R1835 1 35 R$18,3 R1061 61 R$10,6 49 36 R183 3 R$18, R106 R$10, R18 R$18 R10 R$10 R1 R$1 R$

RESUMO Objetivo Analisar os investimentos do Sistema Único de Saúde do Brasil destinados à vocologia. Métodos Estudo ecológico, de caráter quantitativo com dados públicos, secundários, disponibilizados na plataforma digital DataSUS/TABNet. Os dados referem-se à quantidade e aos valores dos procedimentos da vocologia, apresentados e aprovados durante o período de 2008 a 2022 no Brasil. Após a coleta e análise descritiva dos dados, foram adotados os valores absolutos, relativos, taxas de crescimento e déficit. Resultados No período analisado foram realizados 4.6 milhões de procedimentos realizados a um custo total de R$18.350 milhões. Destes, 2.4 milhões de procedimentos foram aprovados a receberem o pagamento pelas secretarias de saúde dos estados e municípios a um custo total de R$ 10.617 milhões aos cofres públicos. Estes valores repassados representaram uma taxa de crescimento nos investimentos destinados aos procedimentos da vocologia em até 491%, se comparado ao ano de 2008, porém acumulou-se uma taxa de déficit financeiro de até 360% em todo o período estudado. Conclusão Constatou-se que os investimentos públicos destinados à vocologia passaram por crescimento significativo em todos os índices analisados, apesar de não terem sido repassados a totalidade dos valores referentes aos procedimentos realizados. ecológico secundários DataSUSTABNet DataSUS TABNet DataSUS/TABNet referemse referem 200 202 absolutos relativos 46 4 6 4. R18350 R 18 350 R$18.35 Destes 24 2 2. 10617 10 617 10.61 491 491% acumulouse acumulou 360 estudado Constatouse Constatou analisados 20 R1835 1 35 R$18.3 1061 61 10.6 49 36 R183 3 R$18. 106 10. R18 R$18 R1 R$1

Abstract Purpose: To analyze, histomorphologically, the influence of the geometry of nanostructured hydroxyapatite and alginate (HAn/Alg) composites in the initial phase of the bone repair. Methods: Fifteen rats were distributed to three groups: MiHA - bone defect filled with HAn/Alg microspheres; GrHA - bone defect filled with HAn/Alg granules; and DV - empty bone defect; evaluated after 15 days postoperatively. The experimental surgical model was the critical bone defect, ≅8.5 mm, in rat calvaria. After euthanasia the specimens were embedded in paraffin and stained with hematoxylin and eosin, picrosirius and Masson-Goldner’s trichrome. Results: The histomorphologic analysis showed, in the MiHA, deposition of osteoid matrix within some microspheres and circumjacent to the others, near the bone edges. In GrHA, the deposition of this matrix was scarce inside and adjacent to the granules. In these two groups, chronic granulomatous inflammation was noted, more evident in GrHA. In the DV, it was observed bone neoformation restricted to the bone edges and formation of connective tissue with reduced thickness in relation to the bone edges, throughout the defect. Conclusion: The geometry of the biomaterials was determinant in the tissue response, since the microspheres showed more favorable to the bone regeneration in relation to the granules.

ABSTRACT Objective: This study aimed to evaluate bone repair in rat dental sockets after implanting nanostructured carbonated hydroxyapatite/sodium alginate (CHA) and nanostructured carbonated hydroxyapatite/sodium alginate containing 5% strontium microspheres (SrCHA) as bone substitute materials. Methods: Twenty male Wistar rats were randomly divided into two experimental groups: CHA and SrCHA (n=5/period/group). After one and 6 weeks of extraction of the right maxillary central incisor and biomaterial implantation, 5 μm bone blocks were obtained for histomorphometric evaluation. The parameters evaluated were remaining biomaterial, loose connective tissue and newly formed bone in a standard area. Statistical analysis was performed by Mann-Withney and and Wilcoxon tests at 95% level of significance. Results: The histomorphometric results showed that the microspheres showed similar fragmentation and bio-absorbation (p>0.05). We observed the formation of new bones in both groups during the same experimental periods; however, the new bone formation differed significantly between the weeks 1 and 6 (p=0.0039) in both groups. Conclusion: The CHA and SrCHA biomaterials were biocompatible, osteoconductive and bioabsorbable, indicating their great potential for clinical use as bone substitutes.

ABSTRACT Objective: Based on a literature review and on our own experience, this study proposes sheep as an experimental model to evaluate the bioactive capacity of bone substitute biomaterials, dental implant systems and orthopedics devices. The literature review covered relevant databases available on the Internet from 1990 until to date, and was supplemented by our own experience. Methods: For its resemblance in size and weight to humans, sheep are quite suitable for use as an experimental model. However, information about their utility as an experimental model is limited. The different stages involving sheep experiments were discussed, including the care during breeding and maintenance of the animals obtaining specimens for laboratory processing, and highlighting the unnecessary euthanasia of animals at the end of study, in accordance to the guidelines of the 3Rs Program. Results: All experiments have been completed without any complications regarding the animals and allowed us to evaluate hypotheses and explain their mechanisms. Conclusion: The sheep is an excellent animal model for evaluation of biomaterial for bone regeneration and dental implant osseointegration. From an ethical point of view, one sheep allows for up to 12 implants per animal, permitting to keep them alive at the end of the experiments. Level of Evidence II, Retrospective Study.