Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.

Objectives: Increasing resistance of microorganisms and particularly tolerance of bacterial biofilms against antibiotics require the need for alternative antimicrobial substances. S. aureus is the most frequent pathogen causing vascular graft infections. In order to evaluate the antimicrobial efficacy, quantification of the bacterial biofilms is necessary. Aim of the present study was the validation of an in vitro model for quantification of bacterial biofilm on vascular graft surfaces using three different assays. Methods: Standardized discs of vascular graft material (Dacron or PTFE) or polystyrene (PS) as control surface with 0.25 cm² surface area were inoculated with 10⁻³ diluted overnight culture of three biofilm-producing S. aureus isolates (BEB-029, BEB-295, SH1000) in 96-well PS culture plates. After incubation for 4 and 18 h, the biofilm was determined by three different methods: (a) mitochondrial ATP concentration as measure of bacterial viability (ATP), (b) crystal violet staining (Cry), and (c) vital cell count by calculation of colony-forming units (CFU). The experiments were performed three times. Quadruplicates were used for each isolate, time point, and method. In parallel, bacterial biofilms were documented via scanning electron microscopy. Results: All three methods could quantify biofilms on the PS control. Time needed was 0:40, 13:10, and 14:30 h for ATP, Cry, and CFU, respectively. The Cry assay could not be used for vascular graft surfaces due to high unspecific background staining. However, ATP assay and CFU count showed comparable results on vascular graft material and control. The correlations between ATP and CFU assay differed according to the surface and incubation time and were significant only after 4 h on Dacron (BEB-029, p = 0.013) and on PS (BEB-029, p < 0.001). Between ATP and Cry assay on PS, a significant correlation could be detected after 4 h (BEB-295, p = 0.027) and after 18 h (all three strains, p < 0.026). The reproducibility of the ATP-assay presented as inter-assay-variance of 2.1 and as intra-assay variance of 8.1 on polystyrene. Conclusion: The in-vitro model reproducibly quantifies biofilm on standardized vascular graft surfaces with ATP assay as detection system. The ATP assay allows accelerated microbial quantification, however the correlation with the CFU assay may be strain- and surface-dependent.

Robot-assisted gait training (RAGT) provides a task-based support of walking using exoskeletons. Evidence shows moderate, but positive effects in the therapy of patients with cerebral palsy (CP). This study investigates the impact of RAGT on walking speed and gait parameters in pediatric CP patients. Thirty subjects (male = 23; female = 7), with a mean age of 13.0 ± 2.5 (9–17) years, and with spastic CP, were recruited. The intervention group (n = 15) underwent six 20-minute RAGT sessions with the Hybrid Assistive Limb (HAL) during an 11-day hospital stay. Additionally, a therapy concept including physiotherapy, physician-performed manual medicine, massage and exercise therapy was provided. The control group (n = 15) was treated with the therapy concept only. The outcome was based on a 10-Metre Walking Test (10MWT), 6-Minute Walking Test (6MWT), Gross Motor Function Measure (GMFM-88) and lower extremities passive range of motion. The intervention group achieved a mean increase in walking speed in the 10MWT (self-selected walking speed SSW) of 5.5 s (p = 0.378). There were no significant differences between the groups in the 10MWT (max) (p = 0.123) and the 6MWT (p = 0.8). Changes in the GMFM (total) and in the dimension standing and walking, running and jumping (D + E) showed clinically relevant significant results (p = 0.002 and p = 0.046). RAGT as a supplement to an inpatient therapy stay appears to have a positive, yet not significant impact on the gait parameters of pediatric CP patients as well as motivating them to practice walking. Further studies with adapted study designs are needed to evaluate different influencing factors.

Peripheral arterial disease, particularly critical limb ischemia, is an area with urgent need for optimized therapies because, to date, vascular interventions often have limited life spans. In spite of initial encouraging technical success after femoropopliteal percutaneous transluminal angioplasty or stenting, postprocedural restenosis remains the major problem. The challenging idea behind the drug-coated balloon (DCB) concept is the biological modification of the injury response after balloon dilatation. Antiproliferative drugs administered via DCBs or drug-eluting stents are able to suppress neointimal hyperplasia, the main cause of restenosis. This article reviews the results of DCB treatments of femoropopliteal and infrapopliteal lesions in comparison to standard angioplasty with uncoated balloons. A systematic literature search was performed in 1) medical journals (ie, MEDLINE), 2) international registers for clinical studies (ie, www.clinicaltrials.gov), and 3) abstracts of scientific sessions. Several controlled randomized trials with follow-up periods of up to 5 years demonstrated the efficacy of paclitaxel –DCB technology. However, calcified lesions seem to affect the efficacy of DCB. Combinations of preconditioning methods with DCBs showed promising results. Although the mechanical abrasion of calcium via atherectomy or laser ablation showed favorable periprocedural results, the long-term impact on restenosis and clinical outcome has to be demonstrated. Major advantages of the DCBs are the rapid delivery of drug at uniform concentrations with a single dose, their efficacy in areas wherein stents have been contraindicated until now (ie, bifurcation, ostial lesions), and in leaving no stent scaffold behind. Reinterventions are easier to perform because DCBs leave no metal behind. Various combinations of DCBs with other treatment modalities may prove to be viable options in future. The follow-up results of clinical studies will evaluate the long-term impact of DCBs.

Background: During joint replacement, surgical vacuum suction guarantees a sufficient overview on the situs. We assume high concentrations of mesenchymal stromal cells (MSCs) on surgical vacuum filters.We compared the in vitro proliferative and differentiation potency of cells from the following: (i) bone marrow (BM), (ii) cancellous bone (CB), (iii) vacuum filter (VF), and (iv) cell saver filtrate reservoir (SF) in 32 patients undergoing elective total hip replacement.Methods: Mononuclear cells (MNC) were isolated, and cell proliferation and colony-forming units (CFU) were measured. Adherent cells were characterized by flow cytometry for MSC surface markers. Cells were incubated with osteogenic, adipogenic, and chondrogenic stimuli. Cells were cytochemically stained and osteoblastic expression (RUNX-2, ALP, and BMP-2) investigated via qPCR.Results: Dependent on the source, initial MNC amount as well as CFU number was significantly different whereas generation time did not vary significantly. CFU numbers from VF were superior to those from SR, BM, and CB. The resulting amount of MSC from the respective source was highest in the vacuum filter followed by reservoir, aspirate, and cancellous bone. Cells from all groups could be differentiated into the three mesenchymal lines demonstrating their stemness nature. However, gene expression of osteoblastic markers did not differ significantly between the groups.Conclusion: We conclude that surgical vacuum filters are able to concentrate tissue with relevant amounts of MSCs. A new potent source of autologous regeneration material with clinical significance is identified. Further clinical studies have to elucidate the regenerative potential of this material in an autologous setting.