Research progress of traditional Chinese medicine regulating related signaling pathways to promote tendon-bone healing / 中国药房

Tendon-bone healing is a complex biological process. Multiple signaling pathways are involved in tendon-bone healing， including transforming growth factor-β signaling pathway， bone morphogenetic protein signaling pathway， Wnt signaling pathway， fibroblast growth factor signaling pathway and nuclear transcription factor-κB signaling pathway. This paper summarizes the research status of traditional Chinese medicine regulating related signaling pathways to promote tendon-bone healing. It is found that a variety of traditional Chinese medicine monomers or herbal extracts （such as baicalein， icariin， total flavonoids of Drynaria fortunei， parthenolide， total saponins of Panax notoginseng， etc.） and traditional Chinese medicine compounds （such as Taohong siwu decoction， Liuwei dihuang pill， Xujin jiegu liquid， etc.） can promote bone formation， anti-inflammatory， anti-oxidation， by regulating the above signaling pathways， thereby effectively promoting tendon-bone healing.

Study on injectable chitosan hydrogel with tendon-derived stem cells for enhancing rotator cuff tendon-to-bone healing / 中国修复重建外科杂志

OBJECTIVE@#To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits.@*METHODS@#TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties.@*RESULTS@#CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05).@*CONCLUSION@#TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.

Suckermouth catfish bone extract as bone graft raw material for bone-healing promotes bone growth in bone loss / Extrato de osso de bagre como material de reparo promove o crescimento ósseo em perda óssea

Objective: This study aimed to evaluate the properties of suckermouth catfish bone extract, which allows it to be adopted as a raw material for bone graft following its graft in an artificial defect of a rat model. Material and Methods: Hydroxyapatite (HA) from suckermouth catfish bone extract was characterized using Fourier-transform infrared spectroscopy (FTIR), and its toxicity was evaluated by Brine Shrimp Lethality Test (BSLT). This material was grafted on artificial defects in rats' femoral bones, which were observed immunologically by Enzyme-linked immunosorbent assay (ELISA) after one week and four weeks, and radiographically in the second week, and histologically in the second and fourth weeks. Results: FTIR shows that this material consists of phosphate, hydroxyl, and carbonate groups, while the BSLT results show that this material is not toxic. Observations by ELISA showed an increase in the expression of Tumor necrosis factor alpha (TNF-α) in defects with HA in the fourth week. Radiographically the defect did not show closure in the second week. In contrast, histological analysis showed a better bone healing process in the defect, which was applied with the HA of the suckermouth catfish bone. Conclusion: The HA extracted from the suckermouth catfish bone has beneficial properties as an alternative to bone graft raw material and, more investigated needed to support this biomaterial to be used in the treatment of bone loss (AU)

Objetivo: Avaliar as propriedades do extrato de osso de bagre, que permitem sua adoção como material bruto para enxerto ósseo, em um defeito ósseo artificial em ratos. Material e Métodos: A hidroxiapatita (HA) do extrato de osso de bagre foi caracterizada usando espectroscopia infravermelha por transformada de Fourier (FTIR), e sua toxicidade foi avaliada pelo Teste de Letalidade do Camarão de Sal (BSLT). Esse material foi enxertado em defeitos artificiais nos ossos femorais de ratos. Análise imunológica por meio do ensaio imunoenzimático (ELISA) foi realizada uma e quatro semanas após a colocação dos enxertos. Análises radiográficas foram feitas na segunda semana e histológica na segunda e quarta semanas. Resultados: A FTIR mostrou que esse material é composto por grupos de fosfato, hidroxila e carbonato, enquanto os resultados do BSLT mostraram que esse material não é tóxico. As observações pelo ELISA mostraram um aumento na expressão do fator de necrose tumoral alfa (TNF-α) nos defeitos com HA na quarta semana. Radiograficamente, o defeito não apresentou fechamento na segunda semana. Em contraste, a análise histológica mostrou um melhor processo de cicatrização óssea no defeito que foi aplicado com a HA do osso de bagre. Conclusão: A HA extraída do osso de bagre possui propriedades benéficas como alternativa ao material bruto para enxerto ósseo, sendo necessárias mais investigações para apoiar esse biomaterial a ser usado no tratamento da perda óssea.(AU)

Research on Runx2 gene induced differentiation of human amniotic mesenchymal stem cells into ligament fibroblasts in vitro and promotion of tendon-bone healing in rabbits / 中国修复重建外科杂志

OBJECTIVE@#To investigate whether the Runx2 gene can induce the differentiation of human amniotic mesenchymal stem cells (hAMSCs) to ligament fibroblasts in vitro and promote the tendon-bone healing in rabbits.@*METHODS@#hAMSCs were isolated from the placentas voluntarily donated from healthy parturients and passaged, and then identified by flow cytometric identification. Adenoviral vectors carrying Runx2 gene (Ad-Runx2) and empty vector adenovirus (Ad-NC) were constructed and viral titer assay; then, the 3rd generation hAMSCs were transfected with Ad-Runx2 (Ad-Runx2 group) or Ad-NC (Ad-NC group). The real-time fluorescence quantitative PCR and Western blot were used to detect Runx2 gene and protein expression to verify the effectiveness of Ad-Runx2 transfection of hAMSCs; and at 3 and 7 days after transfection, real-time fluorescence quantitative PCR was further used to detect the expressions of ligament fibroblast-related genes [vascular endothelial growth factor (VEGF), collagen type Ⅰ, Fibronectin, and Tenascin-C]. The hAMSCs were used as a blank control group. The hAMSCs, hAMSCs transfected with Ad-NC, and hAMSCs were mixed with Matrigel according to the ratio of 1 : 1 and 1 : 2 to construct the cell-scaffold compound. Cell proliferation was detected by cell counting kit 8 (CCK-8) assay, and the corresponding cell-scaffold compound with better proliferation were taken for subsequent animal experiments. Twelve New Zealand white rabbits were randomly divided into 4 groups of sham operation group (Sham group), anterior cruciate ligament reconstruction group (ACLR group), anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-NC-scaffold compound group (Ad-NC group), and anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-Runx2-scaffold compound group (Ad-Runx2 group), with 3 rabbits in each group. After preparing the ACL reconstruction model, the Ad-NC group and the Ad-Runx2 group injected the optimal hAMSCs-Matrigel compunds into the bone channel correspondingly. The samples were taken for gross, histological (HE staining and sirius red staining), and immunofluorescence staining observation at 1 month after operation to evaluate the inflammatory cell infiltration as well as collagen and Tenascin-C content in the ligament tissues.@*RESULTS@#Flow cytometric identification of the isolated cells conformed to the phenotypic characteristics of MSCs. The Runx2 gene was successfully transfected into hAMSCs. Compared with the Ad-NC group, the relative expressions of VEGF and collagen type Ⅰ genes in the Ad-Runx2 group significantly increased at 3 and 7 days after transfection ( P<0.05), Fibronectin significantly increased at 3 days ( P<0.05), and Tenascin-C significantly increased at 3 days and decreased at 7 days ( P<0.05). CCK-8 detection showed that there was no significant difference ( P>0.05) in the cell proliferation between groups and between different time points after mixed culture of two ratios. So the cell-scaffold compound constructed in the ratio of 1∶1 was selected for subsequent experiments. Animal experiments showed that at 1 month after operation, the continuity of the grafted tendon was complete in all groups; HE staining showed that the tissue repair in the Ad-Runx2 group was better and there were fewer inflammatory cells when compared with the ACLR group and the Ad-NC group; sirius red staining and immunofluorescence staining showed that the Ad-Runx2 group had more collagen typeⅠ and Ⅲ fibers, tending to form a normal ACL structure. However, the fluorescence intensity of Tenascin-C protein was weakening when compared to the ACLR and Ad-NC groups.@*CONCLUSION@#Runx2 gene transfection of hAMSCs induces directed differentiation to ligament fibroblasts and promotes tendon-bone healing in reconstructed anterior cruciate ligament in rabbits.

Research progress on bioactive strategies for promoting tendon graft healing after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To review the bioactive strategies that enhance tendon graft healing after anterior cruciate ligament reconstruction (ACLR), and to provide insights for improving the therapeutic outcomes of ACLR.@*METHODS@#The domestic and foreign literature related to the bioactive strategies for promoting the healing of tendon grafts after ACLR was extensively reviewed and summarized.@*RESULTS@#At present, there are several kinds of bioactive materials related to tendon graft healing after ACLR: growth factors, cells, biodegradable implants/tissue derivatives. By constructing a complex interface simulating the matrix, environment, and regulatory factors required for the growth of native anterior cruciate ligament (ACL), the growth of transplanted tendons is regulated at different levels, thus promoting the healing of tendon grafts. Although the effectiveness of ACLR has been significantly improved in most studies, most of them are still limited to the early stage of animal experiments, and there is still a long way to go from the real clinical promotion. In addition, limited by the current preparation technology, the bionics of the interface still stays at the micron and millimeter level, and tends to be morphological bionics, and the research on the signal mechanism pathway is still insufficient.@*CONCLUSION@#With the further study of ACL anatomy, development, and the improvement of preparation technology, the research of bioactive strategies to promote the healing of tendon grafts after ACLR is expected to be further promoted.

Effect of Kartogenin combined with adipose-derived stem cells on tendon-bone healing after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effect of Kartogenin (KGN) combined with adipose-derived stem cells (ADSCs) on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in rabbits.@*METHODS@#After the primary ADSCs were cultured by passaging, the 3rd generation cells were cultured with 10 μmol/L KGN solution for 72 hours. The supernatant of KGN-ADSCs was harvested and mixed with fibrin glue at a ratio of 1∶1; the 3rd generation ADSCs were mixed with fibrin glue as a control. Eighty adult New Zealand white rabbits were taken and randomly divided into 4 groups: saline group (group A), ADSCs group (group B), KGN-ADSCs group (group C), and sham-operated group (group D). After the ACL reconstruction model was prepared in groups A-C, the saline, the mixture of ADSCs and fibrin glue, and the mixture of supernatant of KGN-ADSCs and fibrin glue were injected into the tendon-bone interface and tendon gap, respectively. ACL was only exposed without other treatment in group D. The general conditions of the animals were observed after operation. At 6 and 12 weeks, the tendon-bone interface tissues and ACL specimens were taken and the tendon-bone healing was observed by HE staining, c-Jun N-terminal kinase (JNK) immunohistochemical staining, and TUNEL apoptosis assay. The fibroblasts were counted, and the positive expression rate of JNK protein and apoptosis index (AI) were measured. At the same time point, the tensile strength test was performed to measure the maximum load and the maximum tensile distance to observe the biomechanical properties.@*RESULTS@#Twenty-eight rabbits were excluded from the study due to incision infection or death, and finally 12, 12, 12, and 16 rabbits in groups A-D were included in the study, respectively. After operation, the tendon-bone interface of groups A and B healed poorly, while group C healed well. At 6 and 12 weeks, the number of fibroblasts and positive expression rate of JNK protein in group C were significantly higher than those of groups A, B, and D (P<0.05). Compared with 6 weeks, the number of fibroblasts gradually decreased and the positive expression rate of JNK protein and AI decreased in group C at 12 weeks after operation, with significant differences (P<0.05). Biomechanical tests showed that the maximum loads at 6 and 12 weeks after operation in group C were higher than in groups A and B, but lower than those in group D, while the maximum tensile distance results were opposite, but the differences between groups were significant (P<0.05).@*CONCLUSION@#After ACL reconstruction, local injection of a mixture of KGN-ADSCs and fibrin glue can promote the tendon-bone healing and enhance the mechanical strength and tensile resistance of the tendon-bone interface.

Fracture healing, the diamond concept under the scope: Hydroxyapatite and the hexagon / Consolidación de fractura, una mirada al concepto diamante: Hidroxiapatita y el hexágono

Abstract Bone healing after a fracture has many intercalated steps that depend on the host, type of injury, and often the orthopedist. The diamond concept since 2007 has outlined 4 main facets that have to be considered as a model by the treating surgeon at the time of injury and when nonunion develops: osteogenic cells, osteoconductive scaffolds, osteoinduction, and the biomechanical environment. All of these foment fracture healing in optimal circumstances. Yet, this work proposes other facets, such as osteoimmunology and vascularity, to be considered as well in the model. These are as important as the original four, though their correlation to the original work has been less noted until more recent literature. The mindset of the orthopedist must thoroughly analyze all these facets and many more when dealing with nonunion. This work presents, probably the most sig nificant ones, parting from the original 4-corner diamond model and expanding it to a more representative hexagon integrated model. Metaphorically, just like the strongest inorganic constituent of the bone: hydroxyapatite.

Resumen Hay múltiples pasos intercalados en la consolidación de la fractura que dependen del paciente, el tipo de fractura y frecuentemente del ortopedista. Desde su introducción en el año 2007, el concepto del diamante ha delineado 4 facetas o aristas principales que se han de tener en cuenta por el ortopedista en el momento de la lesión y cuando la no-unión de fractura ocurre: células osteogénicas, matrices osteocunductivas, osteoinducción, y el ambiente biomecánico. Otras facetas para tener en cuenta, no menos importantes, son la osteoimmunología y la vascularidad. Estas son tan importantes como las 4 facetas originales, pero la correlación entre las mismas ha sido poco notada o integrada hasta ahora. El ortopedista tratante debe analizar todas ellas en profundidad, especialmente cuando se trata de una no-unión. Este trabajo presenta las más significantes, partiendo del modelo original del diamante de 4 facetas hacia uno más representativo e integrado como el hexágono. Metafóricamente, como el elemento inorgánico más abundante y fuerte en el hueso: la hidroxiapatita.

Three osteotomy methods and bone healing in Ilizarov tibial bone transport / 中华创伤骨科杂志

Objective:To explore the effects of 3 osteotomy methods on the bone healing in Ilizarov tibial bone transport.Methods:The data of 93 patients were retrospectively reviewed who had been treated by Ilizarov single-segment tibial bone transport at Department of Hand Surgery, The Second Hospital of Tangshan from December 2003 to April 2019. Minimally invasive osteotomy was performed in 16 patients [group A: 16 males with an age of (37.1±8.3) years; 5 cases of type Ⅱ and 11 ones of type Ⅲ by Gustilo classification], subperiosteal saw osteotomy in 57 patients [group B: 47 males and 10 females with an age of (39.1±11.8) years; 17 cases of type Ⅱ and 40 ones of type Ⅲ by Gustilo classification] and extraperiosteal wire saw osteotomy in 20 patients [group C: 19 males and one female with an age of (37.7±11.2) years; 18 cases of type Ⅱ and 2 cases of type Ⅲ by Gustilo classification]. The 3 groups were compared in terms of the bone healing index and the Association for the Study and Application of the Method of Ilizarov (ASAMI) functional scores.Results:The 3 groups were comparable because there was no significant difference in the preoperative general data between them ( P>0.05). All the patients were followed up for 19 to 50 months (average, 27.4 months). All patients achieved bony healing, and their associated complications were cured after corresponding treatments. There were no significant differences in the bone healing index between the 3 groups [(53.09±21.88) d/cm for group A, (59.97±33.29) d/cm for group B and (46.20±14.11) d/cm for group C] ( P>0.05). There were no significant differences either in the good to excellent rate by the ASAMI functional scores between the 3 groups (87.5% for group A, 89.5% for group B and 90.0% for group C) ( P> 0.05). Conclusion:All the 3 osteotomy methods may achieve good bony union, leading to similar bone healing indexes and postoperative functional scores.

Stiffness and Stress Distribution of Internal Fixation System for Long Bone Fractures / 医用生物力学

Objective To study distributions of stiffness and stress of each component in internal fixation system for long bone fractures composed of fractured bones (including callus) and bone plates,and propose a method for determining bending stiffness of fracture internal fixation implants. Methods Based on the linear bending theory and composite beam theory, the mechanical model of femoral shaft internal fracture fixing system composed of fractured bones and bone plate was constructed and verified with the finite element model based on artificial femur CT data. The relationship between stress and stiffness of the internal fixation system for long bone fractures was established. Results The three stages (slow-rapid-steady growth) for variation of fractured bone bending stiffness with callus elastic modulus obtained by calculation and analysis were consistent with the three stages of actual bone healing process, which proved accuracy of the theoretical calculation method. Changing patterns for the neutral axis position of internal fracture fixing system composed of fractured bones and bone plate were further obtained, namely, the neutral axis position was close to (away from) the central axis of bone plate when stiffness of bone plate increased (decreased). According to the stress required for fracture healing (0.72-0.80 MPa), the reasonable range for bending stiffness of bone plate was 0.99-4.20 kN·mm2. Conclusions When elastic modulus of the callus was 0.037.00 GPa, bending stiffness of the fractured bones increased rapidly, which was at the stage of bone bridge formation. When elastic modulus of the callus was above 7 GPa, the callus tended to mature. Based on the femur model in this study, when thickness of bone plate was 3.6-6.0 mm and elastic modulus of fractured bones was 3.013.5 GPa, the entire fractured bone section could be effectively stimulated. In this study, when bending stiffness of bone plate was 0.99-4.20 kN·mm2 during the generation stage of bone bridge, it was conducive to bone healing.

Effect of low intensity ultra sound on bone regeneration and healing: a systematic review

ABSTRACT Objective: Low Intensity Pulsed Ultra Sound (LIPUS) is found to have stimulatory effect on bone healing and regeneration. This review aimed to assess whether LIPUS enhances bone regeneration and healing in terms of efficiency in improving clinical, radiographic, histologic parameters or serum and tissue biomarkers. Methods: A comprehensive search based on PRISMA guidelines with pre-determined eligibility criteria was conducted to identify randomized controlled clinical trials evaluating effectiveness of Low intensity pulsed ultrasound in bone regeneration and healing. The title and abstract of the entries in all languages yielded from the PubMed, Google scholar and Cochrane library were screened. Results: 14 eligible Randomized controlled trials testing the effectiveness of LIPUS was evaluated. More heterogeneity was seen in the screened studies with respect to sample characteristics, type of bone and outcome measures. The studies that screened histological parameters state that LIPUS is significantly beneficial than control. In terms of time for radiographic union, most of the studies stated that LIPUS was more effective than control but numberof studies are very few. Whereas studies which evaluated parameters such as healing time and radiographic union were showing highly inconsistent results regarding effectiveness of LIPUS. Conclusion: This review cannot give a definitive conclusion that LIPUS is effective in bone healing with respect to clinical parameters but a positive influence on radiographical and histological parameters in bone healing and regeneration is promising to pursue future research.

Evaluation of alkaline phosphatase as a biomarker in the healing progression following tooth extraction / Avaliação da fosfatase alcalina como um biomarcador na progressão da cicatrização após extração dentária

Objetivo: A progressão da cicatrização de um alvéolo após uma extração é geralmente analisada por meio de exame clínico e investigação radiográfica. Embora a cicatrização do tecido mole geralmente seja mantida bem, a progressão da cicatrização do tecido duro é mais difícil de prever e gerenciar, com problemas como alvéolo seco ou má união do osso subjacente. Biomarcadores séricos para progressão da cicatrização óssea, como a Fosfatase Alcalina (FAL), podem ser úteis como ferramenta diagnóstica para intervenção precoce. Material e Métodos:Vinte indivíduos saudáveis de 18-30 anos de idade que deveriam extrair dentes do siso inferiores impactados foram incluídos. Foram coletados 2 ml de sangue, antes do tratamento e 48 horas depois, as amostras seguintes foram coletadas 1 mês, 2 meses e 3 meses após o procedimento. As radiografias intraorais foram realizadas no final dos três meses. Resultados: Houve uma correlação obtida com a cura e os níveis de FAL em intervalos de tempo de 1, 2 e 3 meses (p <0,05), onde 17 pacientes que tiveram um aumento substancial nos níveis de FAL também tiveram cura satisfatória após três meses. Três indivíduos que não apresentaram aumento no nível de FAL não tiveram cura satisfatória. Conclusão: FAL é um biomarcador suplementar útil para a consolidação óssea (AU)

Objective: The progression of a healing socket following an extraction is usually analysed through clinical examination and radiographic investigation. Whilst soft tissue healing is usually maintained well, healing progression of hard tissue is more challenging to predict and manage, with issues such as a dry socket or mal-union of the underlying bone. Serum biomarkers for bone healing progression, such as alkaline phosphatase (ALP), could prove helpful as a diagnostic tool for early intervention. Material and Methods: Twenty healthy 18-30-year-old individuals who were to extract lower impacted wisdom teeth were included. 2ml of blood was collected before treatment, 48 hours after then following samples were collected 1 month, 2 months and 3 months after the procedure. Intra-oral radiographs were taken at the end of the three months. Results: There was a significant correlation elicited with the healing and ALP levels at 1,2 & 3 months' time intervals (p<0.05), where 17 patients who had a substantial increase in the levels of ALP also had satisfactory healing after three months. Three individuals who did not show any increase in ALP level did not have satisfactory healing. Conclusion:ALP is a useful supplementary biomarker for bone healing.(AU)

Characterizations of alveolar repair after mandibular second molar extraction: an experimental study in rats

Abstract Characterizations of rat mandibular second molar extraction socket with significantly different buccal and lingual alveolar ridge width remain unclear. Objective: To observe alterations in the alveolar ridge after extraction of mandibular second molars, and to examine processes of alveolar socket healing in an experimental model of alveolar ridge absorption and preservation. Methodology: Eighteen Wistar rats were included and divided into six groups regarding healing time in the study. Bilateral mandibular second molars were extracted. The rats with tooth extraction sockets took 0, 1.5, 2, 3, 4 and 8 weeks of healing. Histological observation, tartrate-resistant acidic phosphatase (TRAP) staining, Masson's trichrome staining, immunohistochemical staining and micro-computed tomography (micro-CT) were applied to estimate alterations in the alveolar ridge. Results: Different buccal and lingual alveolar ridge width led to different height loss. Lingual wall height (LH) decreased significantly two weeks after tooth extraction. Buccal wall height rarely reduced its higher ridge width. From two to eight weeks after extraction, bone volume (BV/TV), density (BMD), and trabecular thickness (Tb.Th) progressively increased in the alveolar socket, which gradually decreased in Tb.Sp and Tb.N. LH showed no significant change during the same period. Osteogenic marker OCN and OPN increased during bone repair from two to eight weeks. The reduced height of the lingual wall of the tooth extraction socket was rarely repaired in the later repair stage. Osteoclast activity led to absorption of the alveolar ridge of the alveolar bone wall within two weeks after operation. We observed positive expression of EMMPRIN and MMP-9 in osteoclasts that participated in the absorption of the spire region. Conclusion: Extraction of rat mandibular second molars may help the study of alveolar ridge absorption and preservation. The EMMPRIN-MMP-9 pathway may be a candidate for further study on attenuating bone resorption after tooth extraction.

Uso de membrana de colágeno y placa de protección mecánica como instrumento de conservación alveolar / Use of collagen membrane and mechanical protective plate as an instrument for alveolar preservation

Luego de una extracción dental ocurren inevitablemente procesos de reabsorción y remodelación ósea, donde la dimensión y morfología de la cresta alveolar se ve modificada, representando un problema para la rehabilitación de la zona. Estudios clínicos han documentado un promedio de 4,0 a 4,5 mm de reabsorción ósea horizontal luego de una exodoncia, como así también cambios dimensionales significativos en los alrededores del hueso alveolar. El propósito fue evaluar y comparar clínica y tomográficamente los procesos de reparación y conservación del reborde alveolar post-extracción de paredes intactas, con y sin la utilización de esponjas de colágeno intraalveolar como relleno y placa termoformada como barrera física, durante el proceso de cicatrización. Se seleccionaron pacientes con indicación de exodoncia de elementos dentarios normalmente implantados y clínicamente aceptables, aplicando los criterios de exclusión, se realiza toma de impresión del terreno para la confección de una placa de protección rígida 0,8 termoformada para ser colocada posterior a la extracción durante la masticación por un período de 30 días. Se indica tomografía cone-beam post operatoria inmediata y a los tres meses para analizar, medir y comparar alto y ancho de crestas alveolares residuales. En la evaluación clínica y tomográfica de los casos estudiados, el grupo control donde se usó únicamente placa de protección alveolar arrojó mejores resultados que el grupo donde se colocaron esponja de colágeno en el interior del alvéolo. Palabras clave: Regeneración ósea, esponja de colágeno, cicatrización ósea, alvéolo postextracción, placa de protección alveolar (AU)

After a tooth extraction, bone resorption and remodeling processes inevitably occurs, where size and morphology of the alveolar crest is modified, representing a problem for the rehabilitation of the area. Clinical studies have documented an average of 4.0 to 4.5 mm of horizontal bone resorption after an extraction, us well us substantial dimensional changes around the alveolar bone. The purpose was to evaluate and compare clinical and tomographically both repair and preservation of post extraction alveolar ridge of intact walls processes, with and without the use of intraalveolar collagen sponges as filler and a thermoformed protective plaque, us physica? barrier, during healing process. Patients with normally implanted and clinically acceptable tooth with extraction indication were selected, applying the exclusion criteria, impression of the field is taken to build a 0.8 rigid thermoformed protective plaque in order to be placed after extraction and used during chewing for a period of 30 days. Immediate and three months post-operative cone beam tomography are indicated to analyze, measure and compare height and width of residual alveolar crests. In the clinical and tomographic evaluation of the cases treated, control group where only alveolar protective plaque was used, showed better results than the group with intraalveolar collagen sponge (AU)

Application of Wall Thickness Analysis in Estimating the Degree of Tibial Fracture Bone Healing / 医用生物力学

Objective To quantitatively judge the degree of tibial bone healing using the finite element wall thickness analysis method, so as to provide an intuitive diagnostic basis for clinical judgment of tibial union and delayed bone healing. Methods After three-dimensional (3D) modeling for the affected and healthy limb side of 48 patients, the maximum wall thickness (MWT) was calculated, and the ratio (B value) was used as a quantitative index of bone healing. When both BMWT2 and BMWT1 were greater than 0.9, bone healing could be judged. When BMWT2 was between 0.9 and 0.7, bone union was judged to be poor, and there was no significant increase in this value after regular reexamination. When BMWT3 was above 0.9 while both BMWT1 and BMWT2 were smaller than 0.7, it could be judged as internal fixation failure, which should be replaced during the second operation. The clinical diagnosis was revised twice, and the final clinical healing results were observed. Results Clinical diagnosis analysis and finite element wall thickness analysis were carried out in 48 patients during each review period, and 21 cases of delayed bone healing and 27 cases of bone nonunion were judged clinically. Among them, 2 cases were judged to be ineffective, and bone grafting intervention was adopted to replace the internal fixation, 12 cases were judged to be still effective, and all cases were finally healed by surgical intervention of bone grafting alone. By Bowker test, P=0.094 was obtained, indicating that the wall thickness analysis method was consistent with the clinical diagnosis. Conclusions The wall thickness analysis method can be used to quantitatively analyze the degree of bone healing at fracture end and realize the rapid calculation of bone healing degree. The case results in this study show that the finite element wall thickness analysis method is superior to the simple clinical diagnosis method, and has better differential diagnostic significance for early diagnosis of poor bone healing.

Local administration of parathyroid hormone and parathyroid hormone-related peptides for bone tissue engineering / 生物医学工程学杂志

Parathyroid hormone (PTH) exerts multiple effects such as regulating bone remodeling, promoting angiogenesis, etc., and it is an active factor with great application potential for bone repair. In recent years, with the development of scaffold material loading strategies and parathyroid hormone-related peptides (PTHrPs), in situ loading of PTH or PTHrPs on scaffold materials to promote bone defect healing gradually becomes possible. Based on the current status and challenges of intermittent PTH (iPTH) for bone tissue engineering, the review summarizes the in-situ application strategies of PTH and the construction of PTHrPs as well as current problems and further directions in this field, with a view to propel the clinical application of scaffold materials loaded with PTH or PTHrPs

Tendon-bone healing in anterior cruciate ligament reconstruction with and without remnant preservation / 中国组织工程研究

BACKGROUND: Whether remnant preservation can improve tendon-bone healing remains a controversy. Experiments were designed to evaluate whether remnant preservation has the biological advantage of promoting tendon-bone healing by histology and imaging. OBJECTIVE: To investigate the effect of preservation of ligament stump on tendon-bone healing in anterior cruciate ligament reconstruction. METHODS: Forty New Zealand rabbits were randomly divided into two groups: anterior cruciate ligament reconstruction group without remnant preservation (group A) and anterior cruciate ligament reconstruction group with remnant preservation (group B), with 20 rabbits in each group. Achilles tendon was selected as the graft, and the bilateral anterior cruciate ligaments of all the rabbits were cut off. In group A, the anterior cruciate ligament stump was completely removed. In group B, the tibia stump was cut off from the femoral stop, and the tibia stump was retained. According to the position of the anterior cruciate ligament of the normal rabbits, the tibia and the femoral canal were selected for reconstruction. At 6 and 12 weeks after surgery, the expression of vascular endothelial growth factor and hypoxia inducible factor-1α was detected by immunohistochemistry. Graft microvessel density was detected by CD34 immunohistochemical staining. The signal intensity of tendon and the width of bone tunnel were observed by MRI and CT. RESULTS AND CONCLUSION: (1) The percentage of hypoxia inducible factor-1α and vascular endothelial growth factor positive cells in group B was significantly higher than that in group A at 6 weeks after operation (P 0.05). (2) At 6 weeks after operation, the expansion of bone tunnel in group B was significantly lower than that in group A, and the signal intensity of tendon graft was lower in group B than that in group A (P 0.05). (3) In this experiment, in the early stage of ligament reconstruction, the anterior cruciate ligament reconstruction with remnant preservation is superior to the anterior cruciate ligament reconstruction without remnant preservation in terms of graft revascularization and reduction of bone tunnel expansion, showing some biological advantages.

Animal models for study on rotator cuff injury / 中南大学学报(医学版)

Rotator cuff injuries are the most common cause of shoulder pain and dysfunction. Ideal animal shoulder models should have similar shoulder anatomy and function as human, and are able to replicate the microenvironment change after tendon injury. At present, a variety of animal models including rat, mouse, rabbit, sheep, canine, bovine, and primate have been used to study the mechanism of rotator cuff injury, effects of different repair techniques, and factors affecting tendon to bone healing. Although large animal models are more anatomically similar to humans, small animal models are more convenient in revealing the biological mechanism of rotator cuff injury and healing. Choosing appropriate animal models based on research objectives and establishing new small animal models play a critical role in revealing the mechanism of rotator cuff diseases and developing novel treating strategies.

Systemic lithium chloride administration improves tooth extraction wound healing in estrogen-deficient rats

Abstract The purpose of this investigation was to evaluate the effects of lithium chloride (LiCl) on the socket healing of estrogen-deficient rats. Seventy-two rats were allocated into one of the following groups: Control, Ovariectomy and LiCl (150 mg/kg/2 every other day orally) + Ovariectomy. Animals received LiCl or water from the 14th day post-ovariectomy, until the completion of the experiment. On the 21st day after ovariectomy, the first molars were extracted. Rats were euthanized on the 10th, 20th and 30th days following extractions. Bone healing (BH), TRAP positive cells and immunohistochemical staining for OPG, RANKL, BSP, OPN and OCN were evaluated. The Ovariectomy group presented decreased BH compared to the LiCl group at 10 days, and the lowest BH at 20 days (p<0.05). At 30 days, the Ovariectomy and LiCl-groups presented lower BH than that of the Control (p<0.05). The number of TRAP-stained cells was the lowest in the LiCl group at 20 days and the highest in the Ovariectomy group at 30 days (p<0.05). At 10 days of healing, the LiCl group demonstrated stronger staining for all bone markers when compared to the other groups, while the Ovariectomy group presented higher RANKL expression than that of the Control (p<0.05). LiCl enhanced bone healing in rats with estrogen deficiency, particularly in the initial healing phases. However, as data on the effects of lithium chloride on bone tissue are still preliminary, more studies related to its toxicity and protocol of administration are necessary before its application in clinical practice.

Resumo O objetivo deste estudo foi avaliar os efeitos do Cloreto de Lítio (ClLi) na cicatrização de alvéolos de ratas deficientes em estrogênio. Setenta e duas ratas foram alocadas em um dos seguintes grupos: Controle, Ovariectomia e Cloreto de Lítio (150mg/kg/ oralmente a cada 2 dias) + ovarectomia. Os animais receberam ClLi ou água a partir do 14º dia pós-ovariectomia, até a conclusão do experimento. No 21º dia após a ovariectomia, os primeiros molares foram extraídos. As ratas foram sacrificadas nos dias 10, 20 e 30 após extrações. Foram avaliadas a cicatrização óssea (BH), células positivas para TRAP e coloração imuno-histoquímica para OPG, RANKL, BSP, OPN e OCN. O grupo Ovariectomia apresentou BH diminuída em comparação ao grupo LiCl aos 10 dias e a menor BH aos 20 dias (p<0,05). Aos 30 dias, os grupos Ovariectomia e LiCl apresentaram menor BH do que o Controle (p<0,05). O número de células positivas para TRAP foi menor no grupo ClLi em 20 dias e o maior no grupo Ovariectomia em 30 dias (p<0,05). Aos 10 dias de cicatrização, o grupo ClLi demonstrou imunomarcação mais intensa em todos os marcadores testados quando comparado aos outros grupos, enquanto o grupo Ovariectomia apresentou maior expressão de RANKL do que a do controle (p<0,05). O ClLi melhorou a cicatrização óssea em ratos com deficiência de estrogênio, particularmente nas fases iniciais do reparo. No entanto, como os dados sobre os efeitos do cloreto de lítio no tecido ósseo ainda são preliminares, mais estudos relacionados à sua toxicidade e protocolo de administração são necessários antes de sua aplicação na prática clínica.

The Effect of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) on Bone Healing around Osseointegrated Dental Implants - A Systematic Review

NSAIDs are considered effective pain-relieving agents after dental implant placement. However, they may have related side effects. We wanted to determine as to whether these agents have a positive or negative impact on the supporting alveolar bone after dental implant placement. METHODSPRISMA flowchart was followed and the clinical question in PICO format was: ‘‘Do systemic NSAIDs help or impede the healing of osssointergrated implants?’’. The databases of Ovid, PubMed, Scopus, and Web of Science were used in this systematic literature search for clinical trials. Publications between January 1, 1990 and January 31, 2020 were searched. RESULTSThe initial search resulted in 385 articles. Only four studies were selected for qualitative synthesis after fulfilling the eligibility criteria (three double blind randomized controlled trials (RCTs) and one retrospective cohort study) with 222 patients and 686 implants placed. CONCLUSIONSThe results showed that the administration of NSAIDs post implant placement may not have a significant effect on the supporting bone.

Aloenxertos ósseos e enxerto sintético de hidroxiapatita em falha óssea ulnar em galinhas (Gallus gallus domesticus), aspectos radiográficos e histológicos / Bone allografts and synthetic grafts hydroxyapatite on ulnar bone defect in fowl (Gallus gallus domesticus), radiographic and histological aspects

Dos atendimentos ortopédicos realizados em aves no HCV-UFRGS, 86% são fraturas, sendo aproximadamente 30% delas cominutivas com perda óssea expressiva, justificando a importância da utilização de enxertos em fraturas de aves. O objetivo deste trabalho foi avaliar dois aloenxertos e enxerto sintético de hidroxiapatita em defeito ósseo de galinhas. Utilizaram-se 30 galinhas separadas em três grupos: aloenxerto congelado em ultra-freezer (GUF), aloenxerto congelado em nitrogênio líquido (GNL) e enxerto sintético de hidroxiapatita deficiente em cálcio (GHA). Nos três grupos, os enxertos foram aplicados com placas e parafusos bloqueados de 2mm na ulna direita das aves, avaliando-se a evolução por meio de exames radiográficos até serem completados 90 dias de pós-operatório e o resultado final mediante exame histológico. A média e desvio-padrão relacionando o tempo de consolidação óssea radiográfica foi: GNL 61,67±21,79 dias (90% de consolidação), GUF 47,14±13,50 dias (70% de consolidação) e GHA 70±18,17 dias (60% de consolidação). Houve diferença significativa no tempo de consolidação óssea entre o GUF e o GHA. Histologicamente, os enxertos do GUF foram os que estavam em consolidação mais avançada. Os aloenxertos do GNL foram superiores no preenchimento de falha óssea ulnar de galinhas.(AU)

Of the orthopedic visits performed on birds at HCV-UFRGS, 86% are fractures, and approximately 30% of them are comminuted with expressive bone loss, justifying the importance of the use of grafts in bird fractures. The objective of this work was to test two allografts and a synthetic HADC graft on finishing in Gallus gallus domesticus. 30 laying hens were used, divided in three groups: frozen allograft in ultrafreezer (UFG); frozen allograft in liquid nitrogen (LNG); calcium deficient synthetic hydroxyapatite graft (HAG). The three graft groups were exposed to serial radiographs until the 90 postoperative days, as well as the histological examination at the end of the experiment were: LNG 61.67±21.79 days (90% consolidation), UFG 47.14±13.50 days (70% consolidation) and HAG 70±18.17 days (60% consolidation). There was a significant difference in bone healing time between GUF and GHA. Histologically, GUF grafts were the ones that were in the most advanced consolidation. LNG allografts were superior in filling ulnar bone failure of fowl.(AU)