Tim Schwarting

Bone Morphogenetic Protein 7 (BMP-7) Influences Tendon-Bone Integration In Vitro

Introduction Successful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration. Materials and Methods To study the biological effects of BMP-7 on the process of tendon-bone-integration, two independent in vitro models were used. The first model involved the mono- and coculture of bovine tendon specimens and primary bovine osteoblasts with and without BMP-7 exposure. The second model comprised the mono- and coculture of primary bovine osteoblasts and fibroblasts. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lactate and osteocalcin (OCN) were analyzed by ELISA. Histological analysis and electron microscopy of the tendon specimens were performed. Results In both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures. Discussion This study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts. Conclusion Our findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface.

Stimulation with bone morphogenetic protein-2 (BMP-2) enhances bone–tendon integration in vitro

ABSTRACT Purpose: Preclinical studies have reported that bone morphogenetic protein (BMP)-2 promotes bone–tendon healing following anterior cruciate ligament reconstruction. We examined the region-specific effects of BMP-2 on osteoblast and fibroblast differentiation in a highly standardized murine in vitro co-culture model of bone–tendon integration. Materials and methods: We used quantitative PCR to measure the dose- and time-dependent influence of BMP-2 on the expression of alkaline phosphatase, osteocalcin, collagen type 1 (alpha 1 chain), runt-related transcription factor 2, osteopontin, collagen type 1 (alpha 2 chain), collagen type 5 (alpha 1 chain), decorin, fibromodulin, mohawk homeobox, bone morphogenetic protein receptor, type 1A, bone morphogenetic protein receptor, type 2, and Noggin in the osteoblast, interface, and fibroblast regions of a co-culture model of the murine preosteoblast cell line MC3T3-E1 and the fibroblast cell line 3T6. Results: Stimulation with BMP-2 resulted in a significant upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), collagens (p < 0.001), runt-related transcription factor 2 (p < 0.05), and osteopontin (p < 0.001) expression in the osteoblast region. In the interface region, BMP-2 exposure led to dose- and time-dependent upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), osteopontin (p < 0.001), runt-related transcription factor 2 (p < 0.001), and markers of extracellular matrix production (p < 0.001). Both BMP receptors showed a significant BMP-2-dependent upregulation at the interface region, and Noggin was downregulated at the osteoblast and interface region following BMP-2 exposure. Conclusions: Exposure to BMP-2 upregulated the expression of genes associated with bone–tendon integration in vitro, suggesting the stimulation of transdifferentiation processes at the interface and fibroblast regions as well as the induction of positive feedback mechanisms. Further studies will be needed to establish BMP-2 dose and treatment algorithms following tendon reinsertion and reconstruction.

Rehabilitation von Schwerverletzten in Deutschland

BACKGROUND In recent years, there has been an ongoing improvement in the treatment and structural aspects of acute trauma care. Because of the definition of rehabilitation as a post-acute part of the treatment of traumatic injuries, especially in multiple injured patients, there is need to improve the interaction and cooperation between acute care hospitals and rehabilitation clinics. This article gives a survey of the current state of rehabilitation in Germany. MATERIALS AND METHODS Based on a directory of rehabilitation clinics and an internet search, all rehabilitation clinics were identified and included in the analysis for clinic location, structural and equipment attributes. RESULTS In total 551 rehabilitation clinics with expertise in the treatment of traumatic and orthopedic injuries were identified. In detail, broad differences between the federal states could be observed. The number of rehabilitation clinics per state ranged from 1 to 136 and the number of beds from 70 to 18040. The average catchment area covered by a rehabilitation clinic is 648 km(2) (range 149-2106 km(2)) with an average of 1584 patients per clinic per year. Of the clinics 68% can treat patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and 62.1% are able to deal with patients who need renal dialyses. Almost all clinics provide an x-ray facility (96.4%) while computed tomography (CT) and magnetic resonance imaging (MRI) are available in 52.6% and 50.3%, respectively. CONCLUSION The number of rehabilitation clinics available seems to be adequate for all patients with traumatic injuries but there are enormous differences between the federal states. Because rehabilitation is important for the outcome of multiple injured patients, a further improvement of the quality and integration into the regional trauma network seem to be necessary.

Effect of Bone Morphogenetic Protein-2 on Tendon–Bone Integration in an In Vitro Cell Culture

The goal of this study was to evaluate the influence of bone morphogenetic protein-2 (BMP-2) on tendon-bone integration in a bovine in vitro cell culture. Seventy-two bovine tendons were cultivated over 3 months. The effects of BMP-2 were evaluated by generation in 4 subgroups. The groups differed in 2 parameters: the application of BMP-2 and the application of primary bovine osteoblasts. Results were analyzed biochemically by determining alkaline phosphatase activity and histologic tendon calcification, both markers for graft incorporation. Histological analysis demonstrated a positive effect of BMP-2 on the production of extracellular matrix and therefore the induction of osteogenesis. In addition, the results showed a superior cell ingrowth on the tendon in the BMP-2-stimulated groups. Calcium carbonate-like structures and organized ossification zones could only be detected in the BMP-2-stimulated tendons. The histological results matched those of the biochemical alkaline phosphatase analysis. The highest alkaline phosphatase activity was detected using BMP-2 stimulation in the first month (P<.001). High alkaline phosphatase values suggest high osteoblast activity and a high potential for mineralization. Furthermore, a positive effect of BMP-2 on fibroblasts existed with regard to the overall integration process. These results confirm the positive influence and triggering effect of BMP-2 on the mineralization process. Bone morphogenetic protein-2 seems to accelerate and optimize tendon-bone integration in the early process of graft incorporation. Besides the influence of BMP-2 on bovine osteoblasts, an additional positive effect of BMP-2 on bovine fibroblasts was detected; therefore, graft incorporation may be carried out by osteoblasts and fibroblasts.

The osseous morphology of nondegenerated shoulders shows no side-related differences in elderly patients: an analysis of 102 computed tomography scans.

BACKGROUND A precise understanding of glenohumeral anatomy is required to optimize preoperative planning in shoulder joint arthroplasty, which is difficult in the presence of degenerative disease. In unilateral disease, the contralateral shoulder can be used as a representation of normal anatomy; however, intrasubject differences in shoulder morphology have not been investigated. METHODS A retrospective study of all patients aged >65 years who received whole body computed tomography at our trauma center from 2010 through 2014 was conducted. Right and left shoulder computed tomography scans were examined, and the following anatomic parameters were measured: humeral head diameter in anteroposterior and axial views, glenoid diameter in anteroposterior and axial views, glenoid surface, scapula neck depth, neck-shaft angle, glenoid inclination, glenoid/head ratio, and glenoid version. Patients with inadequate scan quality, osseous lesions, pre-existing anatomic abnormality, or metallic implant at the shoulder region and significant osteoarthritis were excluded. RESULTS The study analyzed 102 shoulders of 51 patients. Mean age was 71.4 ± 8.2 years. Humeral head and glenoid diameters, scapula neck depth (right, 36 ± 8 mm; left, 36 ± 7 mm; P = .684), glenoid/head ratio (right, 0.6 ± 0.1; left, 0.6 ± 0.0; P = .961), and glenoid surface (right, 790 ± 152 mm(2); left, 754 ± 134 mm(2); P = .215) showed no significant side-related differences. In addition, no significant difference was found regarding the neck-shaft angle (P = .211) and glenoid anteversion or retroversion (right, 65% [n = 33] anteversion and 35% [n = 18] retroversion; left, 69% [n = 35] anteversion and 31% [n = 16] retroversion; P = .417). CONCLUSION There are no significant side-dependent differences in the osseous anatomy of the glenohumeral joint. In patients with unilateral shoulder degeneration, the contralateral shoulder can provide reference values during the planning of shoulder replacement surgery.

The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model

The effects of cyclooxygenase (COX) inhibition following the reconstruction of the anterior cruciate ligament remain unclear. We examined the effects of selective COX-2 and nonselective COX inhibition on bone-tendon integration in an in vitro model. We measured the dose-dependent effects of ibuprofen and parecoxib on the viability of lipopolysaccharide- (LPS-) stimulated and unstimulated mouse MC3T3-E1 and 3T3 cells, the influence on gene expression at the osteoblast, interface, and fibroblast regions measured by quantitative PCR, and cellular outgrowth assessed on histological sections. Ibuprofen led to a dose-dependent suppression of MC3T3 cell viability, while parecoxib reduced the viability of 3T3 cultures. Exposure to ibuprofen significantly suppressed expression of Alpl (P < 0.01), Bglap (P < 0.001), and Runx2 (P < 0.01), and although parecoxib reduced expression of Alpl (P < 0.001), Fmod (P < 0.001), and Runx2 (P < 0.01), the expression of Bglap was increased (P < 0.01). Microscopic analysis showed a reduction in cellular outgrowth in LPS-stimulated cultures following exposure to ibuprofen and parecoxib. Nonselective COX inhibition and the specific inhibition of COX-2 led to region-specific reductions in markers of calcification and cell viability. We suggest further in vitro and in vivo studies examining the biologic and biomechanical effects of selective and nonselective COX inhibition.

RETRACTED ARTICLE: The benefit of arthroscopically assisted therapy for concomitant glenohumeral injuries in patients with unstable lateral clavicle fractures

This article has been retracted at the request of the authors. The reason is that the authors have stated that the number of patients at time points investigated as well as data regarding pain levels and functional outcome are incorrect. They would like to express their regrets to the Editor-inChief and the whole Editorial Board. The online version of this article contains the full text of the retracted article as electronic supplementary material.

The relationship between initial closed reduction and the surgical reconstruction of the radiocarpal joint line in distal radial fractures

INTRODUCTION Whilst initial closed reduction followed by definitive open fixation is widely applied in the treatment of distal radial fractures, the effect of the closed reduction on the reconstruction of the articular surface remains unclear. Our research questions were: METHODS Palmar tilt and radiocarpal inclination of 425 patients were measured at admission, following initial closed reduction and after surgical reconstruction. RESULTS Closed reduction increased palmar tilt by 12.1° and radial inclination by 2.7°. Open surgical reduction further corrected palmar tilt by 17.88° and radial inclination by 3.5°. Whilst there was no association between postoperative palmar tilt and initially achieved closed reduction, a significant association between radial inclination following closed reduction and surgical fixation was found. CONCLUSION Our retrospective study challenges the existence of a relationship between the initial closed reduction and the reconstruction of the anatomic joint line in surgically treated distal radial fractures.

Is there a benefit of proximal locking screws in osteoporotic distal radius fractures? – A biomechanical study

INTRODUCTION The distal radial fracture is a common fracture and frequently seen in geriatric patients. During the last years, volar plating has become a popular treatment option. While the application of locking screws at the distal fragment is widely accepted, there is no evidence for their use at the radial shaft. MATERIALS AND METHODS In six osteoporotic pairs of matched human cadaver radii an extra-articular model creating an AO 23-A2.1 fracture was employed. Osteosynthesis were performed using the APTUS 2.5 Adaptive TriLock Distal Radius System (Medartis AG) with locking (LS) or non-locking screws (NLS) for proximal fixation. Biomechanical testing was performed in a staircase fashion: starting with 50 cycles at 200N, the load was continuously increased by 50N every 80 cycles up to a maximum force of 400N. Finally, load to failure was analyzed with failure defined as sudden loss of force measured (20%) or major deformation of the radii (10mm). RESULTS At 200N, 250N, 300N, 400N and load to failure, the NLS group showed a higher degree of elastic modulus. In contrast, the LS group showed higher elastic modulus at 350N. Maximum force was higher in the LS group without reaching statistical significance. Reasons for loss of fixation were longitudinal shaft fractures, horizontal peri-implant fractures and distal cutting out. No difference was seen between the two groups concerning the development of the above mentioned complications. CONCLUSION Our study did not show biomechanical superiority for distal radius fracture fixation by using locking screws in the proximal holes in an osteoporotic cadaver study. At load to failure, longitudinal shaft fractures and peri-implant fractures seemed to be a more relevant problem rather than failure of the proximal fixation.

Surgical complications following ESIN for clavicular mid-shaft fractures do not limit functional or patient-perceived outcome

Elastic intramedullary nailing (ESIN) has been proposed as an alternative minimal-invasive method for the operative management of mid-shaft fractures of the clavicle. However, a relevant complication rate has been reported in previous cohorts. The present retrospective single-centre study aimed to analyse the complications following ESIN in adult patients with clavicular mid-shaft fractures (Allman type I) and their impact on functional and patient-perceived outcome measures. Results were compared to a control group receiving locking plate osteosynthesis. The clinical course and outcome of operatively managed patients with clavicular mid-shaft fractures were retrospectively analysed. Patients were assigned to group A (ESIN) and group B (plate fixation). Radiological, functional (Constant Murley Shoulder Outcome Score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) Score, the Oxford Shoulder Score (OSS)), and patient perceived aesthetic and clinical outcome were measured. A total of 47 (33 male, 14 female) operatively managed patients with a mean age of 26.7 ± 14.9 years and a follow up time of 38.1 ± 19.4 months were analysed. 36 patients were treated by ESIN (Group A), whereas 11 patients received open reduction and internal plate fixation (Group B). Patients were operatively treated with a mean delay of 7.4 ± 9.3 days (group A: 6.6 ± 8.7 days, group B: 10.2 ± 11.1 days, p=0.326) between trauma and the surgical index procedure. There were no significant differences in the functional (CS: p=0.338, DASH: p=0.247, OSS: p=0.434) and patient-perceived (p=0.346) outcome measures between both groups. Surgical complications were noted in 14 patients (group A: 12, group B: 2) and non-union in 4 patients (group A: 3, group B: 1). There was no correlation between the recorded complications as assessed by the Clavien and Dindo classification and the functional as well as the patient-perceived outcome measures. Despite a relevant incidence rate of surgical complications, ESIN provides good to excellent functional and patient-perceived results in the treatment of clavicular mid-shaft fractures.