The HIPGEN study funded under EU Horizon 2020 (Grant 7792939) has the aim to investigate the potential of the first regenerative cell therapy for the improvement of recovery after muscle injury in hip fracture patients. For this aim we intramuscularly injected placental derived mesenchymal stromal cells during hip fracture arthroplasty. Despite not having reached the primary endpoint, which was the Short Physical Performance Battery, we could observe an increase in abductor muscle strength and a faster return to balance looking at symmetry in insole measurements during follow up.
Years ago, we identified the need of a dedicated group and conference for advanced therapies with musculoskeletal indications. We saw a disconnect between high-level science and the criticality of actual medical need, thus creating a gap between research and industry – a gap that needed to be bridged. To achieve this goal, a vehicle to connect and amplify the expertise of key opinion leaders in advanced therapies in orthopaedics was needed. With that purpose in mind and after years of preparation, the “Advanced Therapies in Orthopaedics Foundation” (ATiO) was established with the aim to create a network consisting of all important stake holders in the field, ranging from clinics & research, to corporates, finance and regulators – an Alliance for Advanced Therapies in Orthopaedics to form the future.
The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.Aims
Methods
In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach. In a retrospective analysis with a standard postoperative follow-up, 95 patients with a PJI of the hip and knee who were treated with a two-stage exchange between 2013 and 2017 formed the study group. A historical cohort of 86 patients treated between 2009 and 2011 not according to the standardized protocol served as a control group. The success of treatment was defined according to the Delphi criteria in a two-year follow-up.Aims
Patients and Methods
Two stage revision is the most commonly used surgical treatment strategy for periprosthetic hip infections (PHI). The aim of our study was to assess the intra- and postoperative complications during and after two stage revision using resection arthroplasty between ex- and reimplantation. In this retrospective cohort study, all patients treated with a two stage revision using resection arthroplasty for PHI were included from 2008 to 2014. During the first stage, the prosthesis was removed resulting in a resection arthroplasty without the use a PMMA spacer. During second stage, (cemented or uncemented) reimplantation of the hip prosthesis was performed. The cohort was stratified into two groups according to the length of prosthesis-free interval (≤10 weeks and >10 weeks). Data on complications during explantation, prosthesis-free interval, reimplantation, and after reimplantation was collected. The overall complication rate between both groups was compared using the chi-squared test. The revision-free and infection-free survival was estimated using Kaplan-Meier survival analysis.Aim
Method
The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (Aims
Patients and Methods
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.
The aim of this study was to identify the incidence of positive
cultures during the second stage of a two-stage revision arthroplasty
and to analyse the association between positive cultures and an
infection-free outcome. This single-centre retrospective review of prospectively collected
data included patients with a periprosthetic joint infection (PJI)
of either the hip or the knee between 2013 and 2015, who were treated
using a standardised diagnostic and therapeutic algorithm with two-stage
exchange. Failure of treatment was assessed according to a definition
determined by a Delphi-based consensus. Logistic regression analysis
was performed to assess the predictors of positive culture and risk
factors for failure. The mean follow-up was 33 months (24 to 48).Aims
Patients and Methods
Despite the lack of data regarding the diagnostic validity of synovial aspiration in Girdlestone hips a Girdlestone-aspiration is often performed before reimplantation to detect a possible persistence of infection during two staged revision total hip arthroplasty (THA). The aim of this study was to assess the diagnostic performance of the synovial aspiration in Girdlestone hips, without a PMMA-Spacer, for the detection of infection persistence prior to THA reimplantation. Seventy four patients undergoing a two staged revision THA surgery between 2006 and 2013 were included in this retrospective cohort study. Both synovial cultures and CRP values were acquired before explantation of the THA and of the Girdlestone hip before reimplantation. An antibiotic holiday of 14 days was observed prior to synovial aspiration. A PJI was defined according to the following criteria: intraarticular presence of pus or a sinus tract, a periprosthetic membrane indicative of infection in the histological analysis, or a positive microbiological isolation in a minimum of two samples.Introduction
Methods
The main reasons for hip prosthesis failure are aseptic loosening and periprosthetic joint infection (PJI). The real frequency of PJI is probably largely underestimated because of non-standardized definition criteria, diagnostic procedure, treatment algorithm and other confounders. Therefore, data from joint registries are not reflecting the frequency of PJI and can be misleading; particularly low-grade PJI can be frequently misdiagnosed as aseptic failure. Therefore, prospective clinical studies with standardized protocol, comprehensive diagnostic procedure and sufficient follow-up should be performed. Sonication of explanted prosthesis is highly sensitive for detection of biofilms on prosthetic surface and allows quantitative analysis of biofilm formation. We hypothesize that by using sonication, ceramic components (BIOLOX®delta, BIOLOX®forte) will show higher resistance against biofilm adhesion compared to polyethylene (PE) and metal (CoCrMo). In this prospective multicentre study (level of evidence: Ia), we included all consecutive adults ≥18 years of age, who underwent explantation of the hip prosthesis for infection or aseptic reason. Excluded were patients in whom part of the prosthetic components were retained. A standardized and comprehensive diagnostic algorithm was applied, including sonication of all removed prosthetic components for qualitative and quantitative microbiological analysis (ultrasound bath 40 kHz, 1 W/cm2, 1 min). Individual components (metal, PE, ceramic) were separately placed in sterile boxes for investigation. All patients were simultaneously included in the European Prosthetic joint infection cohort (EPJIC, Background
Methods
Intact abductors of the hip play a crucial role
in preventing limping and are known to be damaged through the direct lateral
approach. The extent of trauma to the abductors after revision total
hip replacement (THR) is unknown. The aim of this prospective study
was to compare the pre- and post-operative status of the gluteus
medius muscle after revision THR. We prospectively compared changes
in the muscle and limping in 30 patients who were awaiting aseptic
revision THR and 15 patients undergoing primary THR. The direct
lateral approach as described by Hardinge was used for all patients.
MRI scans of the gluteus medius and functional analyses were recorded
pre-operatively and six months post-operatively. The overall mean
fatty degeneration of the gluteus medius increased from 35.8% (1.1
to 98.8) pre-operatively to 41% (1.5 to 99.8) after multiple revision
THRs (p = 0.03). There was a similar pattern after primary THR,
but with considerably less muscle damage (p = 0.001), indicating
progressive muscle damage. Despite an increased incidence of a positive
Trendelenburg sign following revision surgery (p = 0.03) there was
no relationship between the cumulative fatty degeneration in the
gluteus medius and a positive Trendelenburg sign (p = 0.26). The
changes associated with other surgical approaches to the hip warrant
investigation. Cite this article:
Skeletal muscle injuries often lead to severe functional deficits. Mesenchymal stem cell (MSC) therapy is a promising but still experimental tool in the regeneration of muscle function after severe trauma. One of the most important questions, which has to be answered prior to a possible future clinical application is the ideal time of transplantation. Due to the initial inflammatory environment we hypothesized that a local injection of the cells immediately after injury would result in an inferior functional outcome compared to a delayed transplantation. Twenty-seven female Sprague Dawley rats were used for this study. Bone marrow was aspirated from both tibiae of each animal and autologous MSC cultures obtained from the material. The animals were separated into three groups (each n=9) and the left soleus muscles were bluntly crushed in a standardized manner. In group 1 2×106 MSCs were transplanted into the injured muscle immediately after trauma, whereas group 2 and 3 received an injection of saline. Another week later the left soleus muscles of the animals of group 2 were transplanted with the same number of MSCs. Group 1 and 3 received a sham treatment with the application of saline solution in an identical manner. In vivo functional muscle testing was performed four weeks after trauma to quantify muscle regeneration. Maximum contraction forces after twitch stimulation decreased to 39 ± 18 % of the non injured right control side after crush trauma of the soleus muscles as measured in group 3. Tetanic stimulation showed a reduction of the maximum contraction capacity of 72 ± 12 % of the value obtained from intact internal control muscles. The transplantation of 2 x 106 MSCs one week after trauma improved the functional regeneration of the injured muscles as displayed by significantly higher contraction forces in group 2 (twitch: p = 0.014, tetany: p = 0.018). Local transplantation of the same number of MSCs immediately after crush injury was able to enhance the regeneration process to a similar extent with an increase of maximum twitch contraction forces by 73.3 % (p = 0.006) and of maximum tetanic contraction forces by 49.6 % (p = 0.037) compared to the control group. The presented results underline the effectivity of MSC transplantation in the treatment of severe skeletal muscle injuries. The most surprising finding was that despite of the fundamental differences of the local environment into which MSCs had been transplanted, similar results could be obtained in respect to functional skeletal muscle regeneration. We assume that the effect of the MSC after immediate injection can partly be explained by their known immunomodulatory competences. The data of our study provide evidence for a large time window of MSC transplantation after muscle trauma.
The development of iron oxide nanoparticles, which are taken up and endosomally stored by stem cells, allows the evaluation of cellular behaviour in the muscle with the use of magnetic resonance imaging (MRI). Previous work has shown that labelling does not affect the proliferation and neurogenic differentiation capacity of embryonic stem cells. In the present study we are currently investigating the in vivo distribution and migration of locally transplanted MSC after blunt muscle trauma in a rat model.
