Local Application of Strontium in a Calcium Phosphate Cement System Accelerates Healing of Soft Tissue Tendon Grafts in Anterior Cruciate Ligament Reconstruction: Experiment Using a Rabbit Model

Background: The healing of soft tissue tendon graft within the bone tunnel in anterior cruciate ligament (ACL) reconstruction is known to be slower than that of bone-patellar tendon-bone graft. There are attempts in accelerating the healing of the graft within the bone tunnel. One of the methods is the use of strontium-enriched calcium phosphate bone cement (Sr-CPC). The early result in animal study was encouraging, though it was not known whether the accelerated healing was solely due to the effect of the strontium within the cement, or due to the calcium phosphate cement (CPC) itself. Hypothesis: There would be differences between a strontium-enriched calcium phosphate cement (Sr-CPC) and a conventional calcium phosphate cement (CPC) in terms of the effect on soft tissue tendon graft healing within the bone tunnels in anterior cruciate ligament (ACL) reconstruction. Study Design: Controlled laboratory study. Methods: Thirty single bundle ACL reconstruction procedures were performed in 15 rabbits with the use of an Achilles tendon allograft. The graft on the left limb was coated with Sr-CPC, while that on the right limb was coated with CPC. Three animals were sacrificed for histological and histomorphometric analysis at 3, 6, 9, 12 and 24 weeks post-operation. Results: In the Sr-CPC group, early Sharpey fiber formation was present at 6 weeks post-operation while early remodeling of a graft-fibrocartilage-bone junction was noted at 12weeks. In the CPC group, early Sharpey fiber formation was only found at 9 to 12 weeks post-operation. At 24 weeks, a direct enthesis was found in both groups. According to histomorphometric score, graft healing in the Sr-CPC group took place 3 weeks faster than that in the CPC group at and before 12 weeks, but there was no difference at 24 weeks. Conclusion: The local application of strontium in a CPC system leads to accelerated graft healing within the bone tunnels. Clinical Relevance: The use of Sr-CPC to enhance graft-bone healing may improve the clinical results of ACL reconstruction using soft tissue tendon graft. Keywords: anterior cruciate ligament (ACL); strontium; calcium phosphate cementpostprin

Use of strontium-enriched bioactive bone cement in enhancing tendon osteointegration in a rabbit anterior cruciate ligament reconstruction model

Conference Theme: Defying the Aging Spine: Our Mission ContinuesConcurrent Free Papers 5 - Sports: no. 5.17Introduction: It was hypothesised that strontium led to accelerated healing of strontium-enriched calcium phosphate cement (Sr-CPC)–treated soft tissue tendon graft within the bone tunnel in anterior cruciate ligament (ACL) reconstruction. This hypothesis was tested in a rabbit ACL reconstruction model using Achilles tendon allograft. Methods: A total of 30 bilateral ACL reconstructions were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, while that on the contralateral limb was treated with CPC. Three were sacrificed for histomorphometric analysis respectively at 3, 6, 9, 12, and 24 weeks after the index operation. Histomorphometric analysis of the healing of graft was done by 2 independent observers in 42 histological zones per animal using a scoring system of 0 to 9. The data were analysed by Mann-Whitney U test. Results: Accelerated healing of the graft within bone tunnel was noted in the strontium-treated limb at 3, 6, 9, and 12 weeks after the operation (p < 0.001) when compared with the CPC-treated limb. Complete healing of the graft by Sharpey’s fibre formation at 9 weeks and early evidence of remodelling into normal ACL insertion site at 12 weeks were noted in the SrCPC group. The healing of the graft in the CPC-treated limb was noted 3 to 6 weeks slower than the Sr-CPC group. Conclusion: Strontium is the main contributing factor leading to accelerated healing of Sr-CPC–treated soft tissue tendon graft in a rabbit ACL reconstruction model.postprin

Use of strontium-enriched bioactive bone cement in enhancing tendon osteointegration in a rabbit anterior cruciate ligament reconstruction model

Conference Theme: Defying the Aging Spine: Our Mission ContinuesConcurrent Free Papers 5 - Sports: no. 5.17Introduction: It was hypothesised that strontium led to accelerated healing of strontium-enriched calcium phosphate cement (Sr-CPC)–treated soft tissue tendon graft within the bone tunnel in anterior cruciate ligament (ACL) reconstruction. This hypothesis was tested in a rabbit ACL reconstruction model using Achilles tendon allograft. Methods: A total of 30 bilateral ACL reconstructions were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, while that on the contralateral limb was treated with CPC. Three were sacrificed for histomorphometric analysis respectively at 3, 6, 9, 12, and 24 weeks after the index operation. Histomorphometric analysis of the healing of graft was done by 2 independent observers in 42 histological zones per animal using a scoring system of 0 to 9. The data were analysed by Mann-Whitney U test. Results: Accelerated healing of the graft within bone tunnel was noted in the strontium-treated limb at 3, 6, 9, and 12 weeks after the operation (p < 0.001) when compared with the CPC-treated limb. Complete healing of the graft by Sharpey’s fibre formation at 9 weeks and early evidence of remodelling into normal ACL insertion site at 12 weeks were noted in the SrCPC group. The healing of the graft in the CPC-treated limb was noted 3 to 6 weeks slower than the Sr-CPC group. Conclusion: Strontium is the main contributing factor leading to accelerated healing of Sr-CPC–treated soft tissue tendon graft in a rabbit ACL reconstruction model.postprin

促進前交叉韌帶重建術後腱-骨愈合的方法學進展

近年来,应用肌腱移植物(如腘绳肌腱)行前交叉韧带重建术越来越普遍。手术的远期疗效关键取决于肌腱移植物能否在骨隧道内获得可靠的腱-骨愈合,腱-骨界面开始仅通过一些Sharpey样纤维连接,其在力学上逊于正常的纤维软骨连接,之后肌腱移植物在骨隧道内需要相当长时间才能获得可靠的腱-骨愈合。因此,在没有获得可靠的腱-骨愈合前,腱-骨界面被认为是'弱点',肌腱移植物容易产生滑移甚至从骨隧道内拔出,最终导致手术失败。因此,如何促进腱-骨愈合是目前研究的热点。本文对相关文献做一综述,重点关注应用于骨隧道局部的一些方法学进展。其中干细胞技术、生长因子的局部应用、基因转染技术以及炎症反应的生物调控技术等均已获得令人振奋的研究成果。生物活性骨水泥的应用以及物理治疗方法也取得可喜的成果。组织工程技术可能成为降低供区并发症的方法 ,尽管目前的研究成果令人鼓舞,但仅基于动物实验,应用于临床实践尚需进一步随机对照临床研究

Daphnia revisited: Local stability and bifurcation theory for physiologically structured population models explained by way of an example

We consider the interaction between a general size-structured consumer population and an unstructured resource. We show that stability properties and bifurcation phenomena can be understood in terms of solutions of a system of two delay equations (a renewal equation for the consumer population birth rate coupled to a delay differetial equation for the resource concentration). As many results for such systems are available, we can draw rigorous conclusions concerning dynamical behaviour from an analysis of a characteristic equation. We derive the characteristic equation for a fairly general class of population models, including those based on the Kooijman-Metz Daphnia model and a model introduced by Gurney-Nisbet and Jones et al., and next obtain various ecological insights by analytical or numerical studies of special cases

Suppression subtractive hybridization coupled with microarray analysis to examine differential expression of genes in virus infected cells

High throughput detection of differential expression of genes is an efficient means of identifying genes and pathways that may play a role in biological systems under certain experimental conditions. There exist a variety of approaches that could be used to identify groups of genes that change in expression in response to a particular stimulus or environment. We here describe the application of suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis for isolation and identification of chicken transcripts that change in expression on infection of host cells with a paramyxovirus. SSH was used for initial isolation of differentially expressed transcripts, a large-scale validation of which was accomplished by microarray analysis. The data reveals a large group of regulated genes constituting many biochemical pathways that could serve as targets for future investigations to explore their role in paramyxovirus pathogenesis. The detailed methods described herein could be useful and adaptable to any biological system for studying changes in gene expression

Variation in RNA expression and genomic DNA content acquired during cell culture

Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14c, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell