Análise Estatística

A análise estatística entre os grupos foi realizada através da comparação entre a porcentagem de osso neoformado, biomaterial e tecido conjuntivo presentes em cada grupo. A descrição quantitativa das áreas foi representada através de descrição paramétrica com médias e desvio padrão. Na análise histomorfométrica o software GraphPad Prism 7 v 1.45 (GraphPad Software, Inc. La Jolla, CA, USA) foi utilizado para a realização dos valores médios e desvio padrão. Foi realizado o teste paramétrico de Shapiro-Wilks seguido de Análise de Variância (ANOVA) e teste de Tukey para a comparação entre os diversos grupos (p<0,05%).

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Randomized clinical trial for the biological evaluation of two nanostructured biphasic calcium phosphate biomaterials as a bone substitute

Running Title: Clinical trial to evaluate two biphasic calcium phosphate

ABSTRACT

Background: The presence of non-resorbable residual granules of HA may

decrease the bone/implant interface. To balance resorption and bone formation, β- TCP compounds applied at different rates have been studied.

Purpose: The aim of this trial was to compare the clinical, histological, and

histomorphometric responses of two new β-TCP biomaterials in fresh dental sockets after three and six months.

Materials and Methods: Forty-eight volunteers were divided into 4 groups of 12

individuals in a random and double-blind manner: Clot (C), BoneCeramic® _(BC),

Biomaterial 1 (B1), and Biomaterial 2 (B2) groups. Three and six months later, samples were obtained, and histological and histomorphometric sections were evaluated, focusing on the presence of fibrous connective tissue (CT) and newly formed bone. Statistical analysis was performed (p<0.05%).

Results: The quantification of crystalline phases showed that B1 was composed of

HA (60.28%) and β-TCP (39.72%); B2 was composed of HA (78.21%) and β-TCP (21.79%); and BC was composed of HA (61%) and β-TCP (39%). The B1 group showed the most newly formed bone (69.3%6.03%), followed by the BC (51.612.34%), B2 (46.67.66%), and C groups (45.47.98%), and less connective tissue and biomaterial remained in the B1 group after 6 months.

Conclusion: The B1 group samples showed the greatest amount of newly formed

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INTRODUCTION

Ridge preservation measures, which include the filling of extraction sockets with bone substitutes, have been shown to reduce ridge resorption1_{. Human}

re-entry studies recorded horizontal bone loss of 29 to 63% and vertical bone loss of 11 to 22% during the first 6 months after tooth removal2_{. A previous systematic}

review showed that the alveolar ridge undergoes a mean horizontal reduction in width of 3.8 mm and a mean vertical reduction in height of 1.24 mm within 6 months after tooth extraction3_{. Moreover, the resorption rate can increase if any pathological}

or traumatic process causes destruction of one or more of the alveolar bone walls. In this case, part of the defect will be filled by connective tissue, which consequently influences both the planning and predictability of osseointegration4_{. Furthermore,}

dental implant placement at locations with insufficient bone can cause changes in the shape and length of the prosthetic crowns, battlements, and emergence profile, leading to unsatisfactory aesthetic and functional results5-7_.

Considering the difficulties related to obtaining autogenous grafts, as well as their unpredictability, experts have been using different resorbable osteoconductive biomaterials to fill post-extraction sockets to maintain a more adequate bone volume and preserve an alveolar architecture that will favor dental implant installation1, 6-13_{. HA, the main constituent of the inorganic phase of bone, is}

employed in various areas of medicine and dentistry due to its chemical and structural characteristics. Compound and pure synthetic forms of HA do not cause an exacerbated or undesired inflammatory response and are neither antigenic nor carcinogenic. Additionally, they may serve as mineral a tank promoting bone formation and are considered by some authors to be bioactive materials, making them potentially suitable as a substitute material for human bone implants and prostheses11, 14, 15_{. However, the presence of non-resorbable residual granules of HA}

in the socket may decrease the bone/implant interface4_{. Thus, the indication for its}

use is related to the morphology of the socket, the extent of the defect and the desired type of repair16_.

There are many processes involved in the synthesis of apatites, resulting in materials with various physicochemical and biological characteristics, which may make them more or less bioabsorbable14_{. Among the available calcium}

phosphate-based ceramics, synthetic β-tricalcium phosphate ceramics (β-TCP) are osteoconductive biomaterials with an enormous capacity for reabsorption, presenting

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very satisfactory clinical and histological results compared with other ceramics, both in animals and in humans7, 6, 12, 13, 17-19_{. However, pure compounds of β-TCP do not}

present a balance between the resorption rate and bone formation. Thus, β-TCP has been combined with HA with the aim of maintaining a framework in the implanted area for a longer time due to the inability of HA to be reabsorbed. β-TCP is absorbed more rapidly, allowing the creation of spaces to be filled by osteoprogenitor cells and speeding up the process of bone regeneration13, 19-21_{. Advances in nanotechnology}

open up new possibilities for producing biomimetic materials that resemble the in vivo cell growth environment at a nanoscale level22_{. Nanotechnology involves the creation}

of functional materials, devices, and systems through the control of matter at a nanometer length scale (1–100 nm). The application of nanotechnology to biomedical materials is explained by the ability of cells to interact with nanometric features23_.

To establish the best biological response in humans, this study aimed to histologically and histomorphometrically assess two nanostructured synthetic biphasic calcium phosphate biomaterials and to compare them with another synthetic commercially available biomaterial that is widely used in dentistry (BoneCeramic®_).