Comparative Assessment of Contact Osteogenesis at the Titanium Implant-Bone Junction in Male Rabbits with Dissimilar Femoral Defects / Evaluación Comparativa de la Osteogénesis de Contacto en la Unión entre el Hueso y el Implante de Titanio en Conejos Macho con Defectos Femorales Diferentes

SUMMARY: Traumatized bone tissue has the capacity to repair itself so that it eventually regains its almost original form, even in the case of artificially inserted implants. The process that stays at the base of the regeneration is represented by osteogenesis or remote osteogenesis. The major difference between the two types of bone formation is the location of the cement line, which is located on the surface of the implant for contact osteogenesis and on the surface of the bone defect for remote osteogenesis. The aim of the present study was to assess the contact osteogenesis in the case of inserted titanium screws in holes with diameters of 1.8 mm and 1 mm respectively. The obtained results show, in the case of the groove with 1.8 mm that the newly proliferated bone represents 73.85 % of the total area, while in the case of the groove with 1 mm in diameter the value of the newly proliferated bone is 26.15 %. In conclusion, the insertion of titanium screws by self-tapping into the hole smaller than the core of the screw is accompanied by bone proliferation by contact osteogenesis much more modest than in the case of insertion into the hole larger than the core of the screw.

El tejido óseo traumatizado tiene la capacidad de reparar en forma espontánea, de modo que eventualmente recupera su forma casi original, incluso en el caso de implantes insertados artificialmente. El proceso que queda en la base de la regeneración está representado por la osteogénesis u osteogénesis a distancia. La principal diferencia entre los dos tipos de formación ósea es la ubicación de la línea de cemento, que se encuentra en la superficie del implante para la osteogénesis de contacto y en la superficie del defecto óseo para la osteogénesis remota. El objetivo del presente estudio fue evaluar la osteogénesis de contacto en el caso de tornillos de titanio insertados en forámenes con diámetros de 1,8 mm y 1 mm respectivamente. Los resultados obtenidos muestran, en el caso del surco de 1,8 mm que el hueso neoproliferado representa el 73,85 % del área total, mientras que en el caso del surco de 1 mm de diámetro el valor del hueso neoproliferado es del 26,15 %. En conclusión, la inserción de tornillos de titanio por autorroscantes en el foramen menor que el núcleo del tornillo se acompaña de una proliferación ósea por osteogénesis de contacto mucho más modesta que en el caso de la inserción en el foramen mayor que el núcleo del tornillo.

Electrochemical Studies of Magnesium Coated with Modified Chitosan and Electrosprayed as an Anticorrosive Protection Method in Bone Repair / Estudios Electroquímicos del Magnesio Recubierto con Quitosano Modificado y Electrorociado como Proceso de Protección Anticorrosiva en la Reparación de Hueso

ABSTRACT Magnesium (Mg) is essential for the metabolic reactions of the human body and is known for its biocompatibility, its mechanical and physical properties are similar to human bone, which is why it is considered to have high potential in biomedical applications such as temporary and resorbable implants. Through surface modifications, the high tendency to corrosion of Mg could be controlled, such as biodegradable membranes that prevent the passage of chloride ions present in the human organism. To prepare the membrane, solutions of chitosan modified with gelatin and/or glutaraldehyde are used and by means of the electrospray method applied to protect the Mg. To simulate body fluid conditions a Kokubo saline solution (BFK) was prepared. The study focuses on evaluating the corrosion rate of Mg with a coating made of a chitosan electrosprayed membrane, applying electrochemical measurements of electrochemical impedance spectroscopy and linear polarization resistance. The key additive to improve the behavior of the membranes was observed with the use of gelatin, where the membrane with the best results lowing corrosion rates is the Mg CH+GE+GL system, which it was observed with very good physical integrity in the images of morphological analyzes of the surface after 30 days of exposure.

RESUMEN El magnesio (Mg) es esencial para las reacciones metabólicas del cuerpo humano y es conocido por su biocompatibilidad, sus propiedades mecánicas y físicas son similares a las del hueso humano, por lo que se considera que tiene un alto potencial en aplicaciones biomédicas como implantes temporales y reabsorbibles. Mediante modificaciones superficiales se podría controlar la alta tendencia a la corrosión del Mg, como por ejemplo membranas biodegradables que impidan el paso de iones cloruro presentes en el organismo humano. Para preparar la membrana se utilizan soluciones de quitosano modificado con grenetina y/o glutaraldehído y mediante el método de electrorociado se aplican para proteger el Mg. Para simular las condiciones de los fluidos corporales se preparó una solución salina de Kokubo. El estudio se enfoca en evaluar la velocidad de corrosión del Mg con un recubrimiento hecho de una membrana electrorociada con quitosano, aplicando técnicas electroquímicas de espectroscopia de impedancia electroquímica y resistencia de polarización lineal. El aditivo clave para mejorar el comportamiento de las membranas se observó con el uso de gelatina, donde la membrana con mejores resultados bajando los índices de corrosión es el sistema Mg CH+GR+GL, el cual se observó con muy buena integridad física en las imágenes de análisis morfológicos de la superficie después de 30 días de exposición.

Clinical application of β-tricalcium phosphate artificial bone material for alveolar cleft repair / 口腔疾病防治

Objective@# To investigate the osteogenic effect of β-tricalcium phosphate (β-TCP) and bone morphogenetic protein-2 (BMP-2) in the repair of the alveolar cleft.@*Methods @# Fifty-nine patients with unilateral alveolar cleft who visited Capital Medical University School of Stomatology from January 2016 to May 2021 were included. They were divided into three groups according to the different bone repair materials: autologous bone, β-TCP and BMP-2 +β-TCP. The preoperative and postoperative CBCT data of the patients were imported into Mimics 21.0 software. The preoperative volume of the bone defect and the new volume of bone formation were calculated by the three-dimensional reconstruction method. The osteogenesis rate was calculated to evaluate the osteogenesis effect@*Results@#The wounds in the three groups healed well after the operation, without implant material discharge, infection, dehiscence, rejection or other symptoms. Twelve months after the operation, CBCT scanning and three⁃dimensional reconstruction images of the three groups of patients showed the formation of new bone bridges in the alveolar ridge fissure area. The image density of the new bone tissue was not significantly different from that of normal bone tissue, and the continuity of the maxilla was re⁃ stored to varying degrees. The bone rate of autogenous bone was 65.00% ± 16.66%, β⁃ TCP group and BMP⁃2+ β⁃ The bone composition rate of TCP was 69.82% ± 17.60%, 71.35% ± 17.51%, respectively, and there was no significant dif⁃ ference compared with the autogenous bone group (P = 0.382, P = 0.244). The β⁃TCP and BMP⁃2+ β⁃TCP groups had no significant differences in bone rate (P = 0.789). @*Conclusion@#β⁃TCP could be used to replace autologous bone for alveolar cleft repair. The addition of BMP⁃2 to β⁃TCP did not significantly improve the osteogenesis rate.

Microtomographic, histomorphometric, and molecular features show a normal alveolar bone healing process in iNOS-deficient mice along a compensatory upregulation of eNOS and nNOS isoforms

Abstract Inducible nitric oxide synthase (iNOS) is one of the enzymes responsible for the synthesis of nitric oxide (NO), which is an important signaling molecule with effects on blood vessels, leukocytes, and bone cells. However, the role of iNOS in alveolar bone healing remains unclear. This study investigated the role of iNOS in alveolar bone healing after tooth extraction in mice. Methodology C57Bl/6 wild type (WT) and iNOS genetically deficient (iNOS-KO) mice were subjected to upper incision tooth extraction, and alveolar bone healing was evaluated by micro-computed tomography (μCT) and histological/histomorphometric, birefringence, and molecular methods. Results The expression of iNOS had very low control conditions, whereas a significant increase is observed in healing sites of WT mice, where iNOS mRNA levels peak at 7d time point, followed by a relative decrease at 14d and 21d. Regarding bone healing, both WT and iNOS-KO groups showed the usual phases characterized by the presence of clots, granulation tissue development along the inflammatory cell infiltration, angiogenesis, proliferation of fibroblasts and extracellular matrix synthesis, bone neoformation, and remodeling. The overall micro-computed tomography and histomorphometric and birefringence analyses showed similar bone healing readouts when WT and iNOS-KO strains are compared. Likewise, Real-Time PCR array analysis shows an overall similar gene expression pattern (including bone formation, bone resorption, and inflammatory and immunological markers) in healing sites of WT and iNOS-KO mice. Moreover, molecular analysis shows that nNOS and eNOS were significantly upregulated in the iNOS-KO group, suggesting that other NOS isoforms could compensate the absence of iNOS. Conclusion The absence of iNOS does not result in a significant modulation of bone healing readouts in iNOS-KO mice. The upregulation of nNOS and eNOS may compensate iNOS absence, explaining the similar bone healing outcome in WT and iNOS-KO strains.

Preparation and osteogenic properties of hydrogel scaffolds with different concentrations of laponite / 中华创伤骨科杂志

Objective:To prepare the hydrogel scaffolds with different concentrations of laponite and compare their osteogenic properties.Methods:The scaffolds of gelatin/sodium alginate hydrogel into which laponite was added according to the mass ratios of 0%, 1%, 2%, and 3% were assigned into groups T0, T1, T2, and T3. In each group, the compressive modulus was measured and the leaching solution for 24 h extracted to measure the ion release. Bone marrow mesenchymal stem cells (BMSCs) were cultured in the extract medium from each group and common medium (blank group) ( n=3) in the in vitro experiments to determine the expression of osteogenic genes Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and type I collagen after 7 days of culture. In the in vivo experiments, the scaffolds were implanted into the femoral condyle defects in rats, and a blank group with no scaffolds was set. The bone repair in each group was evaluated by hematoxylin-eosin(HE) staining and immunohistochemical staining. Results:The compressive modulus in group T2 [(139.05±6.43) kPa] was significantly higher than that in groups T0, T1 and T3 [(68.83±3.76) kPa, (101.18±3.68) kPa and (125.40±3.28) kPa] ( P<0.05). The ion contents of lithium, magnesium and silicon released from the 24 h leaching solution in group T2 were (0.031±0.005) μg/mL, (3.047±0.551) μg/mL and (5.243±0.785) μg/mL, insignificantly different from those in group T3 ( P> 0.05) but significantly larger than those in group T1 ( P>0.05). The in vitro experiments showed that the expression levels of Runx2, ALP and type I collagen in group T2 were 1.59±0.11, 2.02±0.08 and 1.06±0.17, significantly higher than those in the other groups ( P<0.05). HE staining showed that the implanted hydrogel was tightly bound to the bone tissue. Immunohistochemical staining showed that the numbers of Runx2 and osteocalcin positive cells in group T2 were significantly higher than those in the other groups. Conclusions:With ideal biocompatibility, hydrogel scaffolds with different concentrations of laponite can slowly release the decomposed ions of lithium, magnesium and silicon to promote the osteogenic differentiation of BMSCs and the repair of bone defects in vivo. A 2% concentration of laponite in the hydrogel scaffolds may result in the best results.

Biomechanical Environment Regulates Biomimetic Mineralization of Bone Matrix / 医用生物力学

Bone defects have always been an important cause of threat to human health, and artificial biomimetic bone repair replacement materials are currently one of the most effective and feasible solution approaches to treat bone damage. To develop artificial bone biomimetic materials, an in vitro biomimetic mineralization system must be constructed first to study in vitro biomimetic mineralization mechanism of natural bone matrix. Collagen is a template for mineralization, and its properties such as crosslinking degree, diameter, osmotic pressure, and surface charge can all directly affect mineralization progress. The biochemical and mechanical environments in which mineralization occurs are also quite distinct in their effects on mineralization process, particularly noncollagenous proteins and fluid shear stress (FSS). FSS is considered to be the main mechanical stimulation of bone tissues in micro-environment, which is of great significance to bone growth, repair and health maintenance. FSS at different levels and loading regimes has significant effects on transformation of amorphous calcium phosphate to bone apatite, self-assembly and directional alignment of collagen fibrils, and formation of hierarchical intrafibrillar mineralization. In this paper, the factors affecting collagen mineralization and their mechanism were summarized, with focus on regulation of FSS on collagen mineralization, and development direction in future was also prospected.

Evaluation of tissue in repair with natural latex and / or hyaluronic acid in surgical bone defects

Abstract This study evaluated the bone repair in surgical defects of rats treated with hyaluronic acid (HA) associated or not with Hevea brasiliensis fraction protein (F-1). Bone defect were created in 15 albino Wistar rats divided into 3 groups (n=5): Control group (1) - blood clot; HA group (2) - 0.5% hyaluronic acid; HAF1 group (3) - 0.1% F-1 protein fraction dissolved in 0.5% hyaluronic acid. After 4 weeks, the animals were euthanized and the bone repair was evaluated through histomorphometric analysis, zymography and immunohistochemistry. The neoformed bone area did not show a significant difference (p = 0.757), but there was a tendency for bone trabeculation to increase in the groups HA and HAF1. For immunohistochemically analysis, there was a difference in vascular endothelial growth factor (VEGF) labeling (p = 0.023), being higher in the groups HA and HAF1 than the control group. No significant difference in bone sialoprotein (BSP) (p = 0.681), osteocalcin (p = 0.954), however, significant difference in platelet endothelial cell adhesion molecule-1 (CD-31) (p = 0.040), with HAF1 group being significantly lower than the control. For zymographic analysis, there was no significant difference for metalloproteinase-2 (MMP-2) (p = 0.068), but there was a tendency to increase MMP-2 in the HA group. Despite the influence on angiogenic factors and the apparent tendency for greater trabeculation in the HA and HAF1 groups, there was no significant difference in the area of ​​newly formed bone tissue in the analyzed period.

Resumo Este estudo avaliou o reparo ósseo em defeitos cirúrgicos de ratos tratados com ácido hialurônico (AH) associado ou não à fração proteica de Hevea brasiliensis (F-1). Foram criados defeitos ósseos em 15 ratos albinos Wistar divididos em 3 grupos (n = 5): Grupo controle (1) - coágulo sanguíneo; Grupo HA (2) - ácido hialurônico 0,5%; Grupo HAF1 (3) - fração proteica F-1 0,1% dissolvida em ácido hialurônico a 0,5%. Após 4 semanas, os animais foram submetidos à eutanásia e o reparo ósseo avaliado por meio de análise histomorfométrica, zimografia e imunohistoquímica. A área óssea neoformada não apresentou diferença significativa (p = 0,757), mas houve tendência de aumento da trabeculação óssea nos grupos HA e HAF1. Para a análise imunoistoquímica, houve diferença na marcação do fator de crescimento endotelial vascular (VEGF) (p = 0,023), sendo maior nos grupos HA e HAF1 do que no grupo controle. Nenhuma diferença significativa na sialoproteína óssea (BSP) (p = 0,681), osteocalcina (p = 0,954), no entanto, diferenças significativas foram encontradas para a molécula de adesão de células endoteliais plaquetárias-1 (CD-31) (p = 0,040), com o grupo HAF1 sendo significativamente inferior ao controle. Para a análise zimográfica, não houve diferença significativa para metaloproteinase-2 (MMP-2) (p = 0,068), mas houve tendência de aumento da MMP-2 no grupo HA. Apesar da influência sobre os fatores angiogênicos e da aparente tendência de maior trabeculação nos grupos HA e HAF1, não houve diferença significativa na área de tecido ósseo neoformado no período analisado.

Characteristics and manufacturing techniques of collagen/inorganic materials for constructing tissue-engineered bone / 中国组织工程研究

BACKGROUND: At present, the standard method for clinical treatment of bone defects is autologous bone transplantation. However, the source of autologous bone is limited and it can cause new trauma and defects. Therefore, the development of ergonomic tissue-engineered bone has become the trend of repairing bone defects. OBJECTIVE: To summarize the characteristics and manufacturing techniques of collagen/inorganic materials to construct tissue-engineered bone. METHODS: PubMed, Web of Science (January 2000–January 2020) and CNKI (2010–2020) databases were used online to retrieve the relative articles regarding the application of collagen/inorganic composite scaffold. The key words were “collagen; inorganic materials; tissue-engineered bone; bone repair; geometry of bone scaffold” in English and Chinese, respectively. RESULTS AND CONCLUSION: Applying the principle of bionics, collagen composite inorganic materials were used to construct tissue-engineered bones by simulating the composition, structure, and characteristics of natural bones, which is an important direction in the field of bone graft materials. Collagen provides the extracellular matrix effect of the scaffold material, and promotes the migration, adhesion, and proliferation of cells on the scaffold, and accelerates the degradation of the scaffold in the body, and makes the composite scaffold has good biocompatibility and osteoinductivity. Choosing a suitable manufacturing technology to change the geometry of the collagen/inorganic material scaffold, and achieving the best three-dimensional porous nanoscale structure can promote cell adhesion and proliferation, and enhance the bone regeneration capacity of collagen/inorganic material scaffolds. Simultaneously, the surface of collagen/inorganic scaffolds is modified. Stem cells, biological factors, and polymers with osteogenic or angiogenic potential were compounded onto collagen/inorganic material scaffolds, which will improve the poor mechanical properties, insufficient structural stability, and limited bone regeneration capacity of collagen/inorganic material scaffolds. This provides a good idea for the option of tissue-engineered bone graft materials.

Research progress on the Hippo-YAP signaling pathway mediated osteoimmunology in modulating implant osseointegration / 口腔疾病防治

@#Ideal osseointegration is intimately related to favorable osteoimmune properties around dental implants. An increasing number of in vitro and in vivo studies have indicated that the Hippo-YAP signaling pathway is involved in this biological process. In this article, the implicated roles of Hippo-YAP the signaling axis in peri-implant osteoimmunology were summarized by reviewing relevant evolving literature. The discrepancy concerning the Hippo-YAP signaling regulatory effect on osteogenesis and polarization direction were analyzed as well as propose the potential mechanism, which may be caused by the maturation of osteogenesis-related cells and heterogeneity of macrophages. More attention should be given to the requirements of promoting osteogenesis and patterns of regulating the immune microenvironment by Hippo-YAP in future studies.

Efficacy of apolipoprotein 2-Jifusheng in the treatment of osteomyelitis in rabbits / 中国骨伤

OBJECTIVE@#To evaluate the effect of one-stage treatment of bone morphogenetic protein 2 combined with Jifusheng in the experimental model of osteomyelitis in rabbits.@*METHODS@#The model of chronic osteomyelitis of tibia was established in 30 3-month-old male New Zealand white rabbits with a body weight of (2.0±0.5) kg, and the model was verified 4 weeks after operation. Thirty rabbits with osteomyelitis were randomly divided into 3 groups with 10 rabbits in each group (@*RESULTS@#At 4 weeks after operation, 30 rabbits with osteomyelitis were successfully validated. The results of serological examination showed that the hypersensitive C-reactive protein (CRP) and white blood cell count(WBC)in the model group were significantly higher than those in the blank group at 2 and 4 weeks after operation. Eight weeks after treatment, the detection of blood indexes showed that the white blood cell count (WBC)and hypersensitive C reactive protein (CRP)in treatment group A and treatment group B were significantly lower than those in the model group (@*CONCLUSION@#The combined application of apolipoprotein 2-Jifusheng can promote bone repair and reduce the inflammation of the focus. it can treat rabbits with osteomyelitis in one stage, provide objective basis for the formulation of clinical treatment strategy of osteomyelitis and further promote clinical research.

Research progress on bone defect repair materials / 中国骨伤

In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.

Stability as a key factor for bone repair in nonunion of mandibular osteotomy / Estabilidad como factor clave en la reparación de la nonunión de la osteotomía mandibular

Stability is necessary to ensuring proper bone repair after osteotomies and fractures. The aim of this research was to analyze how the repair of pseudoarthrosis sites was affected by different conditions in related to soft tissue. An experimental study was designed with 18 New Zealand rabbits. Six study groups were formed. An osteotomy was performed on the mandibular body of each animal and muscle was installed at the osteotomy site to model pseudoarthrosis. Fixation by surgery was then carried out, using plates and screws. The animals were submitted to euthanasia after 21, 42 and 63 days to make a descriptive comparison of the histological results. No animal was lost during the experiment. In all the samples, bone formation was observed with different degrees of progress. Defects treated with or without removal of the tissue involved in pseudoarthrosis presented comparable bone repair, showing that stability of the bone segments allows the repair of adjacent tissue. In some samples cartilaginous tissue was associated with greater bone formation. Stabilization of the fracture is the key in bone repair; repair occurs whether or not the pseudoarthrosis tissue is removed.

La estabilidad de las osteotomías y de las fracturas son fundamentales para asegurar la adecuada reparación ósea; el objetivo de esta investigación fue analizar la reparación presente en sitios de pseudoartrosis realizando la limpieza de la zona previo a la fijación o manteniendo el tejido de la nounión en el mismo lugar durante la osteosíntesis. Se diseñó un estudio experimental incluyendo 18 conejos de raza Neozelandesa. Se formaron 6 grupos de estudios a quienes se relizó una osteotomía en el cuerpo mandibular y posterior instalación de músculo en el lugar de la osteotomía para fabricar un modelo de pseudoartrosis. En cirugía posterior se fijó con placa y tornillos. Se realizaron eutanasias a los 42 y 63 días para comparar los resultados de forma descriptiva mediante estudio histológico. No fue perdido ningún animal durante el experimento. En todas las muestras evaluadas se observó formación ósea en diferentes niveles de avance; defectos tratados con o sin el retiro del tejido involucrado en la pseudoartrosis presentaron una condición de reparación ósea comparables, determinando que la estabilidad de los segmentos óseos permite la reparación del tejido adyacente. El tejido cartilaginoso se presentó en algunas muestras asociadas a sectores con mayor presencia de formación ósea. La estabilización de la fractura es clave en la reparación ósea; la reparación se produce manteniendo o retirando el tejido presente en la pseudoartrosis.

Calcium phosphate carrying simvastatin enhances bone regeneration: a systematic review

Abstract Several studies have aimed to develop alternative therapeutic biomaterials for bone repair. The purpose of this systematic review was to evaluate how statins carried by calcium phosphate affect the formation and regeneration of bone tissue in animal models when compared to other biomaterials or spontaneous healing. This systematic review followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, the PRISMA guidelines, and the Preclinical Systematic Review & Meta-analysis Facility (SyRF). The protocol of this systematic review was registered in PROSPERO (CRD42018091112) and in CAMARADES. In addition, ARRIVE checklists were followed in order to increase the quality and transparency of the search. An electronic search was performed using the MEDLINE/PubMed, Scopus, SciELO, and PROSPERO library databases. The authors used a specific search strategy for each database, and they also conducted a search in the grey literature and cross-references. The eligibility criteria were animal studies, which evaluated bone repair treated with calcium phosphate as a simvastatin carrier. The selection process yielded 8 studies from the 657 retrieved. All manuscripts concluded that locally applied simvastatin carried by calcium phosphate is biocompatible, enhanced bone repair and induced statistically greater bone formation than cloth or calcium phosphate alone. In conclusion, the pertinent pre-clinical studies evidenced the calcium phosphate biocompatibility and its effectiveness in delivering SIM to improve the repair of bone defects. So, clinical trials are encouraged to investigate the impact of SIM associated with calcium phosphate bone graft in repairing bone defect in humans.

Resumo Muitos estudos objetivaram desenvolver biomateriais terapêuticos alternativos para o reparo ósseo. O objetivo desta revisão sistemática foi avaliar o efeito da estatina carreada por fosfato de cálcio na formação e regeneração de tecido ósseo em modelos animais quando comparado com outros biomateriais ou coágulo. Esta revisão sistemática seguiu as recomendações do Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, e o Preclinical Systematic Review & Meta-analysis Facility (SyRF). O protocolo desta revisão sistemática foi registrado no PROSPERO (CRD42018091112) e no CAMARADES. Além disso, o guia ARRIVE foi utilizado com o objetivo de aumentar a qualidade e transparência do estudo. Uma pesquisa eletrônica foi realizada através do MEDLINE/PubMed, Scopus, SciELO, e biblioteca do PROSPERO. Os autores utilizaram uma estratégia de busca específica para cada base de dados, e uma busca foi conduzida na literatura cinza e nas referências dos artigos selecionados. Os critérios de elegibilidade foram estudos em animais, os quais avaliaram o repara do ósseo tratado com fosfato de cálcio como carreador de estatina. O processo de seleção obteve 8 estudos dos 657 encontrados. Todos os estudos concluíram que a aplicação local da sinvastatina carreada pelo fosfato de cálcio é biocompatível, melhora o reparo ósseo e induz uma formação óssea significantemente maior que coágulo ou fosfato de cálcio sozinho. Em conclusão, os estudos pré-clínicos pertinentes evidenciaram a biocompatibilidade do fosfato de cálcio e sua eficácia na entrega do SIM para melhorar o reparo de defeitos ósseos. Assim, estudos clínicos são encorajados a investigar o impacto do SIM associado ao enxerto ósseo de fosfato de cálcio na reparação de defeito ósseo em humanos.

In Vivo Biological Effects of Marine Biosilica on a Tibial Bone Defect in Rats

Abstract Research on biomaterials of natural origin has gained prominence in the literature. Above all, marine sponges, due to their architecture and structural components, present a promising potential for the engineering of bone tissue. In vitro studies demonstrate that a biosilica of marine sponges has osteogenic potential. However, in vivo works are needed to elucidate the interaction of biosilica (BS) and bone tissue. The objective of the study was to evaluate the morphological and chemical characteristics of BS compared to Bioglass (BG) by scanning electron microscopy (SEM) and X-ray dispersive energy (EDX) spectroscopy. In addition, to evaluate the biological effects of BS, through an experimental model of tibial bone defect using histopathological, histomorphometric, immunohistochemical (IHC) and mechanical tests. SEM and EDX demonstrated the successful extraction of BS. Histopathological analysis demonstrated that Control Group (GC) had greater formation of newly formed bone tissue compared to BG and BS, yet BG bone neoformation was greater than BS. However, BS showed material degradation and granulation tissue formation, with absence of inflammatory process and formation of fibrotic capsule. The results of histomorphometry corroborate with those of histopathology, where it is worth emphasizing the positive influence of BS in osteoblastic activity. IHQ demonstrated positive VEGF and TGF-β immunoexpression for GC, BS and BG. In the mechanical test no significant differences were found. The present results demonstrate the potential of BS in bone repair, further studies are needed other forms of presentation of BS are needed.

Comparative study on icariin and Bu-Shen-Gu-Chi-Wan for alveolar reconstruction in chronic periodontitis in rats / 口腔疾病防治

Objective@#To observe the effects of icariin (ICA) and Bu-Shen-Gu-Chi-Wan on the alveolar bone absorption of chronic periodontitis in rats, and to explore the effect and possible mechanism of ICA in the treatment of chronic periodontitis. @*Methods@#After the establishment of the periodontitis model, the rats were divided into the periodontitis group (group P), ICA high dose group (group H), ICA low dose group (group L) and Bu-Shen-Gu-Chi-Wan treatment group (group B). Each group received treatment for one month and two months, separately, and the serum osteocalcin (OCN) level was measured. Three-dimensional reconstruction was performed after micro computed tomography (micro CT) scanning to measure the bone parameters of specific points, and the distance between the enamel cementum boundary and alveolar crest (CEJ-ABC) was recorded as alveolar bone resorption value. Tissue sections were generated to evaluate the effect of ICA on alveolar bone repair and reconstruction in rats with experimental periodontitis. @*Results@# Compared with the periodontitis group (group P), OCN levels in the serum in treatment groups (groups H, L and B) were decreased significantly (P < 0.05); the values of bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) in treatment groups (groups H, L and B) were significantly higher than that in group P (P < 0.05). Compared with group P, trabecular thickness (Tb.Th) values of groups H and B significantly increased, and trabecular separation (Tb.Sp) of groups H and B significantly decreased (P < 0.05). The changing trend of parameters in group L was the same as that in group H but only after two months of administration. The difference between Tb.Sp values in groups L and P was statistically significant (P < 0.05). Compared with group P, the CEJ-ABC distance significantly reduced in group L (1 month and 2 months after administration), group H (1 month and 2 months after administration), and group B (only 2 months after administration) (P < 0.05).@*Conclusion@#ICA and Bu-Shen-Gu-Chi-Wan improve the alveolar bone resorption in an experimental model of chronic periodontitis in rats, and the mechanism may be related to the regulation of osteocalcin serum levels.

Advantages and disadvantages of repairing large-segment bone defect / 中国组织工程研究

BACKGROUND: The treatment of large-segment bone defect has always been a major problem in clinical orthopedics. The treatment of large-segment bone defect is characterized by long treatment time, high difficulty and high cost. Therefore, it is of great clinical value and significance to study the treatment of large-segment bone defect. OBJECTIVE: To review the current methods of repairing large-segment bone defect and their advantages and disadvantages. METHODS: PubMed, CNKI and Wanfang databases before April 2020 were retrieved by the first author with the keywords of “bone defect, bone repair, bone graft, intramedullary nail technology, Masquelet, bone transport, vascularized bone graft, bone tissue engineering” in English and Chinese, respectively. Forty eligible articles were included to systematically summarize the repair methods and their advantages and disadvantages in the treatment of large-segment bone defect. RESULTS AND CONCLUSION: (1) Currently, the scope of large bone defects is not clearly defined. In clinical practice, long bone defects with poor healing ability and difficult healing by traditional fixation and autogenous bone graft can be regarded as large-segment bone defect according to experience. (2) There are many repair methods, and different methods can play their unique advantages in the treatment process. However, the disadvantages and related complications of different methods should be paid attention to when choosing the treatment method, so as to improve the bone healing rate. (3) It is still necessary to improve and standardize the existing treatment technology of large-segment bone defect to obtain a more satisfactory treatment effect.

Research hotspots and progress of bone repair materials in tissue engineering / 中国组织工程研究

BACKGROUND: With the improvement in medical level, the clinical demand for bone repair materials is gradually Increasing, and the requirements are also getting more and more. OBJECTIVE: To review the related research progress In the field of bone repair materials In recent years, to analyze the advantages and disadvantages of different materials, and to guide future development In this research field. METHODS: A computer-based online search of CNKI, Wanfang, PubMed, Web of Science databases was performed to retrieve papers published during 1950-2019 with the search terms “tissue engineering, bone repair material, bone defect, natural bone material, bone graft replacement material, traditional Chinese medicine” in Chinese and English. A total of over 900 papers were retrieved, and 68 of them were included In the final analysis. RESULTS AND CONCLUSION: In recent year, with the flourish development of bone tissue engineering, the research of bone tissue repair materials is in the ascendant. In addition to optimizing natural bone, a variety of bone graft substitute materials have been developed, for example, natural macromolecule materials, synthetic macromolecule materials, biomedical ceramics materials, biomedical metal materials, etc., but these materials have different properties. Although there are many bone repair materials at present, the Ideal bone repair materials are few. Therefore, bone tissue repair and bone remodeling is still one of the urgent orthopedic problems to be solved In the clinic. In addition, the traditional Chinese medicine for bone repair, such as pyritum combined with modern bone repair materials, can effectively avoid some of the drawbacks of the current bone repair materials, thereby effectively treating bone defect diseases. This deserves In-depth investigation In the field of bone repair.

A comparative study on the bone repair effects of two kinds of tissue regeneration membranes / 中国组织工程研究

BACKGROUND: Our previous study confirmed that BTO/P(VDF-TrFE) piezoelectric nanocomposite membrane containing 5%BTO (BaTO3, BTO) nanoparticles could significantly promote bone marrow mesenchymal stem cells (BMSCs) adhesion, growth, osteogenic differentiation and repair of bone defects due to its bionic potential. However, for clinical applications, it is not clear whether there is any difference between the bone repair effect of this material as a guide for tissue regeneration and that of the existing clinically non-degradable membrane products. OBJECTIVE: To compare the effects of BTO/P(VDF-TrFE) piezoelectric nano-composite membrane materials with commercial PTFE membrane in repairing critical-sized defects of SD rat skull. METHODS: BTO/P(VDF-TrFE) piezoelectric nanocomposite membrane containing 5% BTO nanoparticles was prepared by solution casting method. Scanning electron microscope, atomic force microscope and water contact angle measuring instrument were used to observe the surface morphology, measure the surface roughness and surface hydrophilicity and hydrophobicity of the material. In SD rats (purchased from the Laboratory Animal Center, Beijing University Hospital of Stomatology, China), a 5-mm sized full-thick bone defect was made on both sides of the sagittal suture of the skull. The left bone defect was covered with PTFE membrane (control group). The right bone defect was covered with BTO/P(VDF-TrFE) piezoelectric nano-composite membrane (experimental group). At postoperative 4 and 12 weeks, micro-CT and histological methods were used to evaluate the repair of the skull defect in rats. This study was approved by Animal Ethics Committee, Beijing University Hospital of Stomatology. RESULTS AND CONCLUSION: The piezoelectric nanocomposite membrane had smooth and dense surface and BTO nanoparticles were evenly distributed. PTFE membrane was composed of loose coarse fibers. The piezoelectric nanocomposite membrane had lower surface roughness (P<0.001) and higher hydrophilicity (P<0.001) than PTFE membrane. Micro-CT and histological results showed that at 4 weeks after surgery, new bone formation was found in both groups, but new bone formation was more obvious in the center of the defect in the experimental group than in the control group. At 12 weeks after surgery, bone defects healed in both groups, but the maturity of newly formed bone in the experimental group was greater than that in the control group. These results suggest that BTO/P(VDF-TrFE) piezoelectric nanocomposite membrane containing 5%BTO (BaTO3, BTO) nanoparticles can be used as a membrane guiding tissue regeneration.

Calcium citrate: An interesting organic calcium biomedical material / 中国组织工程研究

BACKGROUND: Calcium citrate has been used as calcium supplement, anticoagulant, anti-inflammatory agent and bone repair material in biomedical fields. OBJECTIVE: To describe the basic properties of calcium citrate, summarize and discuss the preparation process of calcium citrate and its main applications in biomedical field. METHODS: The research literature related to calcium citrate was searched on the Web of science, CNKI, Medline and other databases by computer. The main key words were “calcium citrate, bone repairing material, citrate and calcium phosphate” in English and “calcium citrate, bone repair materials” in Chinese. The searching time was from February 1920 to February 2020. RESULTS AND CONCLUSION: With the development and exploration of medical materials, it is necessary to change the original process to improve the biological activity of medical calcium citrate. It is an inevitable trend to obtain calcium citrate with various micro-morphology and high biological activity by controllable synthesis method. Calcium citrate is widely used as calcium supplement, anti-inflammatory agent, anticoagulant, bone repair material and other non-medical applications. Its advantages are being gradually explored by researchers. The preparation method plays a decisive role in the application field of calcium citrate. Different internal structure and size will bring different application fields, from the smallest chemical bond connection to the macroscopic morphology or mechanical properties. These factors may be the results of the dedicated exploration of researchers.

A novel hydroxyapatite fiber scaffold for three-dimensional cell culture / 中国组织工程研究

BACKGROUND: The dense microstructure of biological scaffolds and the limitation of cell growth microenvironment are the two major difficulties in the application of biological scaffolds in bone tissue repair. OBJECTIVE: To prepare fluffy hydroxyapatite/polylactic acid composite fiber scaffold, so that cells can easily enter into the scaffold and to realize three-dimensional culture of bone marrow mesenchymal stem cells. METHODS: Fluffy hydroxyapatite/polylactic acid composite scaffold was prepared by using modified electrospinning technology combined with biomineralization. The physical and chemical properties of the fiber scaffold were measured and observed. Human bone marrow mesenchymal stem cells were inoculated on the fluffy hydroxyapatite/polylactic acid composite scaffold and traditional hydroxyapatite/polylactic acid composite scaffold. Cell proliferation, adherence and morphological changes were detected. RESULTS AND CONCLUSION: (1) The thickness of hydroxyapatite coating in the fluffy hydroxyapatite/polylactic acid composite scaffold was about 8.3 µm, most of hydroxyapatite fibers were in discrete state with a diameter of 8-14 µm. The fibers were connected by pores, and the pore diameter was (65±35) µm. The surface area, porosity and water absorption of the scaffold were significantly higher than those of the traditional scaffold (P < 0.01). (2) After 12 hours of culture, the adherence of bone marrow mesenchymal stem cells on the two scaffolds was similar, 83% and 81% cells adhered on the traditional and fluffy scaffolds, respectively. (3) After 7 days of culture, the number of proliferated cells in the fluffy hydroxyapatite/polylactic acid composite scaffold was significantly more than that in the traditional hydroxyapatite/polylactic acid composite scaffold (P < 0.01). (4) After 7 days of culture, FDA staining and scanning electric microscopy showed that cell-cell independent shape appeared in the traditional scaffold. A large number of cells appeared in the fluffy scaffold and grew into cell clusters with high cell activity, which formed a cell-fiber construction. These results indicate that this new type hydroxyapatite/polylactic acid composite scaffold is beneficial for cell entry and proliferation.