Clinical Report: Land-Based Versus Pool-Based Exercise for People Awaiting Joint Replacement Surgery of the Hip or Knee: Results of a Randomized Controlled Trial

Background: Individuals with either knee or hip osteoarthritis are at risk of experiencing pain and developing functional limitations (Bennell 2005). In many cases, to alleviate pain and improve one\u27s quality of life, an individual may require a total joint replacement. Despite advances in surgical technique and joint replacement hardware, surgical procedures are not without risk. Conservative treatments, including therapeutic exercise programmes, may improve a patient\u27s status while avoiding the potential risks associated with surgery (pain, medication utilisation, long bouts of rehabilitation, and/ or death). Researchers have demonstrated that some patients may experience improvements in pain and functional abilities after participating in either land-based or aquatic-based exercise programmes (Maurer et al 1999, Hinman et al 2007). However, according to Gill et al (2009), there is paucity of literature addressing post-exercise outcomes in individuals who are scheduled for either hip or knee joint replacement surgery. Aim: To assess self-reported and performance-based functional measures in individuals (who were scheduled to have either a hip or knee joint replacement) after the completion of either a land-based or pool-based exercise programme. Methods: The authors implemented a randomised controlled trial, allocating subjects to either the land-based (n=40) or pool-based (n=42) exercise programme, stratified by the involved joint. Subjects were recruited from a waiting list of patients who were scheduled for either a knee replacement or hip replacement. Each exercise session was performed for one hour over a total period of 12 sessions (2 times a week for 6 weeks). In addition, the authors instructed the subjects to exercise 3 days a week at home (for 30 minutes each session) performing a combination of walking, stationary bicycling, and/or other exercises they performed in class. Self-reported function (as measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), performance-based outcomes (50-foot timed walk and 30-second chair stand test), and psychosocial status (SF-36 MCS) measures were collected prior to treatment, at the end of the 6-week training session, and finally two months later. These data were collected by a blinded assessor. Additionally, daily pre- and post-exercise pain levels were recorded during each session. Results: The authors reported that both pool-based and land-based exercise programmes were effective in reducing pain and increasing function in patients with a diagnosis of either knee or hip arthritis. However, there were no differences between groups for WOMAC pain (p = .614), WOMAC function (p = .739), 50-foot timed walk test p = .173), the 30-second chair stand test (p = .179), or the SF-36 MCS (p = .205). Those who participated in the land-based programme experienced improvements in pain at both assessment periods (p = .000; .015) whereas the participants in the pool-based programme only demonstrated improvements at the first assessment (p = .011; .431). Both groups demonstrated significant functional improvements at the first testing session for performance-based tests as well as demonstrating significant improvement in WOMAC function scores and the 30-second chair stand test at the final assessment session. Those who participated in the pool-based programme experienced a significantly lower daily pain score (p = .005) when compared to those in the land-based programme. Conclusion: The authors report that both training programmes may lead to positive functional outcomes in individuals who are awaiting a joint replacement surgery. In addition, the authors report that those who participated in the pool programme may tolerate the treatment with less post-exercise pain

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2-enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers. KEYWORDS: nanofibers, tissue engineering, human mesenchymal stem cells, PLLA, BMP, VEGF Schofer et al.: Growth Factor Gene Expession in hMSCs TheScientificWorldJOURNAL (2009) 9, 313-319 314 INTRODUCTION The reconstruction of large bony defects after injury or tumor resection often requires the use of graft material. Besides autologous bone grafts, artificial scaffolds based on synthetic biomaterials such as metals, ceramics, polymers, and composites have been developed BMP-2 is a well-studied member of the transforming growth factor beta (TGFβ) family known to induce osteoblast differentiation MATERIAL AND METHODS Construction of Nanofibers and Characterization The preparation of PLLA nanofibers and the incorporation of BMP-2 into the nanofibers, as well as their characterization by scanning electron microscopy (SEM) and analysis of static contact angles of water, has been reported earlier hMSC Isolation, Characterization, and Culture hMSCs were obtained from consenting patients with the approval of the institutional review board. The indication for surgery was primary osteoarthritis of the hip with increasing pain, decreased range of motion, and signs of progressive osteoarthritis in radiographs. The patients had no evidence of other bone or autoimmune diseases. The routinely removed bone was obtained from the proximal femur, while preparing the implant bed. MSCs were isolated and cultured according to the preparation of Pittenger et al. Gene Expression Analysis Extraction of RNA, synthesis of cDNA, as well as quantitative polymerase chain reaction (qPCR) analysis were performed as described earlier Schofer et al.: Growth Factor Gene Expession in hMSCs Statistics All values were expressed as mean ± standard error of different patients as indicated in the text. Normal distribution was analyzed using the Kolmogorov-Smirnov-Test. Significances between the two groups were calculated using Students' t-test in the case of normal distribution. Otherwise, the Mann-Whitney U test was performed. Values of p < 0.05 were considered to be significant and marked with *. All calculations were done using the statistical analysis software SPSS 17.0. RESULTS Gene Expression of VEGF In order to appraise the impact of PLLA nanofibers on angiogenesis, we first analyzed the ability of hMSCs to express VEGF. As shown in Gene Expression of BMP-2 With respect to the expression of BMP-2, a different pattern could be observed. As shown in Influence of BMP-2 Incorporation on the Expression of Growth Factors In order to elucidate whether the incorporation of BMP-2 is sufficient to compensate the decrease in gene expression of growth factors, we analyzed the time-dependent gene expression of VEGF and BMP-2 of hMSCs grown on PLLA-BMP-2 nanofibers and compared it to that obtained of hMSCs cultured on PLLA nanofibers alone. With respect to BMP-2 gene expression, an initial increase was observed when cells were cultured on PLLA-BMP-2 fibers, which normalized during the course of cultivation 316 DISCUSSION PLLA is a biocompatible, biodegradable, and FDA-approved polymer that can easily be electrospun into a 3-D nonwoven networ