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Purpose: This study aimed to investigate the length change patterns of the native deep medial collateral ligament (dMCL) and potential anteromedial reconstructions (AMs) that might be added to a reconstruction of the superficial MCL (sMCL) to better understand the control of anteromedial rotatory instability (AMRI). Methods: Insertion points of the dMCL and potential AM reconstructions were marked with pins (tibial) and eyelets (femoral) in 11 cadaveric knee specimens. Length changes between the pins and eyelets were then tested using threads in a validated kinematics rig with muscle loading of the quadriceps and iliotibial tract. Between 0° and 100° knee flexion, length change pattern of the anterior, middle and posterior part of the dMCL and simulated AM reconstructions were analysed using a rotary encoder. Isometry was tested using the total strain range (TSR). Results: The tibiofemoral distance of the anterior dMCL part lengthened with flexion (+12.7% at 100°), whereas the posterior part slackened with flexion (−12.9% at 100°). The middle part behaved almost isometrically (maximum length: +2.8% at 100°). Depending on the femoral position within the sMCL footprint, AM reconstructions resulted in an increase in length as the knee flexed when a more centred position was used, irrespective of the tibial attachment position. Femoral positioning in the posterior aspect of the sMCL footprint exhibited <4% length change and was slightly less tight in flexion (min TSR = 3.6 ± 1.5%), irrespective of the tibial attachment position. Conclusion: The length change behaviour of potential AM reconstructions in a functionally intact knee is mainly influenced by the position of the femoral attachment, with different tibial attachments having a minimal effect on length change. Surgeons performing AM reconstructions to control AMRI would be advised to choose a femoral graft position in the posterior part of the native sMCL attachment to optimise graft length change behaviour. Given the high frequency of MCL injuries, sufficient restoration of AMRI is essential in isolated and combined ligamentous knee injuries. Level of Evidence: There is no level of evidence as this study was an experimental laboratory study. [ABSTRACT FROM AUTHOR]

Background: Both the superficial medial collateral ligament (sMCL) and the deep MCL (dMCL) contribute to the restraint of anteromedial (AM) rotatory instability (AMRI). Previous studies have not investigated how MCL reconstructions control AMRI. Purpose/Hypothesis: The purpose was to establish the optimal medial reconstruction for restoring normal knee kinematics in an sMCL- and dMCL-deficient knee. It was hypothesized that AMRI would be better controlled with the addition of an anatomically shaped (flat) sMCL reconstruction and with the addition of an AM reconstruction replicating the function of the dMCL. Study Design: Controlled laboratory study. Methods: A 6 degrees of freedom robotic system equipped with a force-torque sensor was used to test 8 unpaired knees in the intact, sMCL/dMCL sectioned, and reconstructed states. Four different reconstructions were assessed. The sMCL was reconstructed with either a single-bundle (SB) or a flattened hamstring graft aimed at better replicating the appearance of the native ligament. These reconstructions were tested with and without an additional AM reconstruction. Simulated laxity tests were performed at 0°, 30°, 60°, and 90° of flexion: 10 N·m valgus rotation, 5 N·m internal and external rotation (ER), and an AM drawer test (combined 134-N anterior tibial drawer in 5 N·m ER). The primary outcome measures of this force-controlled setup were anterior tibial translation (ATT; in mm) and axial tibial rotation (in degrees). Results: Sectioning the sMCL/dMCL increased valgus rotation, ER, and ATT with the simulated AM draw test at all flexion angles. SB sMCL reconstruction was unable to restore ATT, valgus rotation, and ER at 30°, 60°, and 90° of flexion to the intact state (P <.05). Flat MCL reconstruction restored valgus rotation at all flexion angles to the intact state (P >.05). ER was restored at all angles except at 90°, but ATT laxity in response to the AM drawer persisted. Addition of an AM reconstruction improved control of ATT relative to the intact state at all flexion angles (P >.05). Combined flat MCL and AM reconstruction restored knee kinematics closest to the intact state. Conclusion: In a cadaveric model, AMRI resulting from an injured sMCL and dMCL complex could not be restored by an isolated SB sMCL reconstruction. A flat MCL reconstruction or an additional AM procedure, however, better restored medial knee stability. Clinical Relevance: In patients evaluated with a combined valgus and AM rotatory instability, a flat sMCL and an additional AM reconstruction may be superior to an isolated SB sMCL reconstruction. [ABSTRACT FROM AUTHOR]

Background: The treatment of osteochondral defects (OCDs) constitutes a major problem for orthopaedic surgeons. The altered mechanics and the cell types, with associated soluble factors derived from the exposed subchondral bone, are likely responsible for the mechanically and structurally inferior articular cartilage subsequently obtained as a repair tissue. There is therefore an unmet clinical need for bioresponsive biomaterials that allow cell delivery, reduce cell infiltration from the bone marrow, and support chondrogenesis in the presence of joint mechanical loading. Purpose: To develop a cell-laden injectable biomaterial, with bioadhesive properties, low cell invasion, and good mechanoresilience, in which simulated joint loading could induce tissue maturation through the production and activation of transforming growth factor beta 1 (TGF-β1). Study Design: Controlled laboratory study. Methods: Human bone marrow–derived mesenchymal stromal/stem cells were encapsulated in tyramine-modified hyaluronic acid (HA-Tyr) hydrogels, with crosslinking initiated by the addition of horseradish peroxidase (HRP) and various concentrations of hydrogen peroxide (H2O2; 0.3-2 mM). Cytocompatibility and biomechanical and adhesive properties were analyzed by live/dead staining, rheology, and push-out test, respectively. For multiaxial loading, cell-laden hydrogels were subjected to 10% compression superimposed onto a 0.5-N preload and shear loading (±25°) at 1 Hz for 1 hour per day and 5 times a week for 4 weeks. TGF-β1 production and activation were measured by enzyme-linked immunosorbent assay (ELISA). Results: The viscoelastic properties of the cell-laden HA-Tyr hydrogels, as crosslinked with different ratios of HRP and H2O2, were demonstrated for a range of cell densities and HRP/H2O2 concentrations. In the absence of serum supplementation, cell invasion into HA-Tyr hydrogels was minimal to absent. The bonding strength of HA-Tyr to articular cartilage compared favorably with clinically used fibrin gel. Conclusion: HA-Tyr hydrogels can be mechanically conditioned to induce activation of endogenous TGF-b1 produced by the embedded cells. HA-Tyr hydrogels function as cell carriers supporting biomechanically induced production and activation of TGF-β1 and as bioadhesive materials with low cell invasion, suggesting that they hold promise as a novel biomaterial for OCD repair strategies. Clinical Relevance: Leveraging physiological joint mechanics to support chondrogenic graft maturation in an optimized mechanosensitive hydrogel in the absence of exogenous growth factors is of highest interest for OCD repair. [ABSTRACT FROM AUTHOR]

Regulatory focus theory suggests that promoters are more concerned with growth and preventers are more concerned with security. Since coaching is a growth-oriented process, it seems to be more suitable for clients high on promotion than for clients high on prevention. Applying regulatory fit theory, the present research investigates how preventers can also benefit from coaching. First, a study looking at real coaching processes (N1 = 103) found that a higher promotion than prevention focus was indeed related to more coaching success, i.e., satisfaction and approach motivation. Next, testing the hypothesis that fit effects should also be present in coaching, a study using a vignette approach (N2 = 99) shows that participants experiencing a fit between their focus and a promotion versus a prevention coaching indicate a better coaching evaluation than participants experiencing no fit. In three studies (N3a = 120, N3b = 85, N3c = 189), we used an experimental approach and manipulated the regulatory focus of coaching interventions. We found promotion as well as prevention fit effects showing that participants experiencing a fit indicate more coaching success than participants experiencing no fit. Two studies (N4a = 41, N4b = 87) further tested interpersonal fit, i.e., the fit between the coach's and client's regulatory focus. We found promotion as well as prevention fit effects on participants' satisfaction with and trust in a coach (Study 4a) and promotion fit effects on participants' goal attainment and coaching progress (4b). The findings suggest that by adapting coaching to the client's focus, coaching success can be increased not only for promoters but also for preventers. Thus, we found that regulatory fit effects, albeit small to medium, are also present in coaching. Multiple studies assessing multiple variables relevant to coaching showed that the findings differ regarding the interventions used and the variables that we looked at. The practical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Although open-surgical techniques for the reconstruction of the posterolateral corner (PLC) are well established, the use of arthroscopic procedures has recently increased. When compared with open surgical preparation, arthroscopic orientation in the PLC is challenging and anatomic relations may not be familiar. Nevertheless, a profound knowledge of anatomic key structures and possible structures at risk as well as technical variations of arthroscopic approaches are mandatory to allow a precise and safe surgical intervention. Materials and methods: In a cadaveric video demonstration, an anterolateral (AL), anteromedial (AM), posteromedial (PM) and posterolateral (PL) portal, as well as a transseptal approach (TSA) were developed. Key structures of the PLC were defined and sequentially exposed during posterolateral arthroscopy. Finally, anatomic relations of all key structures were demonstrated. Results: All key structures of the PLC can be visualized during arthroscopy. Thereby, careful portal placement is crucial in order to allow an effective exposure. Two alternatives of the TSA were described, depending on the region of interest. The peroneal nerve can be visualized dorsal to the biceps femoris tendon (BT), lateral to the soleus muscle (SM) and about 3 cm distal to the fibular styloid (FS). The distal attachment of the fibular collateral ligament (FCL) can be exposed on the lateral side of the fibular head (FH). The fibular attachment of the popliteofibular ligament (PFL) is exposed at the tip of the FS. Conclusion: Arthroscopy of the posterolateral recessus allows full visualization of all key structures of the posterolateral corner, which provides the basis for anatomic and safe drill channel placement in PLC reconstruction. A sufficient exposure of relevant anatomic landmarks and precise portal preparation reduce the risk of iatrogenic vascular and peroneal nerve injury. [ABSTRACT FROM AUTHOR]

Purpose: Multiple trauma patients have a high risk of missed injuries. The main point of our study was to provide new epidemiological data on hand and forearm injuries in multiple trauma with a focus on those that were missed. Therefore, we used the database of the TraumaRegister DGU®.Methods: In this study, we evaluated anonymous data from 139931 patients aged 1-100 years with multiple trauma in the TraumaRegister DGU® of the German Society for Trauma Surgery from 2007 to 2017. Patients with hand and forearm injuries documented during hospital stay were identified and analyzed. We included fractures, dislocations, tendon injuries, nerve injuries and vessel injuries. Patients with missed hand and forearm injuries were compared with patients with primary diagnosed injuries in view of gender, age, ISS, Abbreviated Injury Score (AIS), Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), trauma mechanism type of injury, hospital stay, RISC II and mortality rate. Missed injuries were defined as injuries that were recently diagnosed and documented in the intensive care unit (ICU).Results: A total of 50459 multiple trauma patients (36.1%) had hand or forearm injuries, and 89472 patients (63.9%) had neither. Patients with hand injuries were younger and were more often involved in car and motorcycle accidents. Severe head trauma was evaluated less frequently, and severe thorax trauma was evaluated more often in patients with hand injuries. The times of diagnosis of hand injuries were documented in 10971 cases. A total of 727 patients (6.6%) with missed hand injuries were registered. The most commonly missed injuries in multiple trauma were 104 carpal fractures/dislocations (11.2%), 195 nerve injuries (25.4%) and 54 tendon injuries (11.4%). Predisposing factors for missing injuries were multiple diagnoses, primary care in the first hospital and direct from emergency room transfer to the ICU.Conclusion: In contrast to previous findings, severely injured patients, especially those with head injuries and GCS of ≤8, were not predisposed to have missed hand injuries compared to patients without severe head trauma. Special attention should be paid to younger patients after traffic accidents with multiple diagnoses and direct transfer to the ICU. [ABSTRACT FROM AUTHOR]

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. [ABSTRACT FROM AUTHOR]

Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo. [ABSTRACT FROM AUTHOR]

Background: Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before. In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice.Methods: HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA. To investigate major sources of HBD-2, its expression and regulation in plasma samples, polymorphonuclear neutrophils (PMN) and human tissue samples of liver and skin were analysed by ELISA. As liver samples of trauma patients are hard to obtain we tried to review findings in an established trauma model. Plasma samples and liver samples of 56 male C57BL/6 N-mice with a thorax trauma and a femur fracture were analysed by ELISA, real-time PCR and immunohistochemistry for murine beta defensin 4 (MBD-4) and compared with the expression of control group without trauma. The induction of HBD-2 expression in cultured hepatocytes (Hep G2) was analysed after incubation with IL-6, supernatant of Staphylococcus aureus (SA) and Lipopolysaccharides (LPS). One possible signalling pathway was tested by blocking toll-like receptor 2 (TLR2) in hepatocytes.Results: Compared to healthy control group, plasma of multiple traumatized patients and mice showed significantly higher defensin levels after trauma. Compared to skin cells, which are known for high beta defensin expression, liver tissue showed less HBD-2 expression, but higher HBD-2 expression compared to PMN. Immunhistochemical staining demonstrated upregulated MBD-4 in hepatocytes of traumatised mice. In HepG2 cells HBD-2 expression could be increased by stimulation with IL-6 and SA. Neutralization of HepG2 cells with αTLR2 showed reduced HBD-2 expression after stimulation with SA.Conclusion: Plasma samples of multiple traumatized patients showed high expression of HBD-2, which may protect the severely injured patient from overwhelming bacterial infection. Our data support the hypothesis that liver is one possible source for HBD-2 in plasma while posttraumatic inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates are a main component in the therapy of osteoporosis and other bone resorptive diseases. Previous studies have shown a positive effect of systemically applied bisphosphonates on fracture healing. Nevertheless high doses are related to side effects like osteonecrosis of the jaw, nephrotoxis and gastrointestinal symptoms. In this study we investigated the effect of locally applied pamidronate on fracture healing.Methods: In a rodent model a simple femur fracture was set in female Wistar rats. We performed intramedullary fixation of the fracture and placed a collagen matrix around the fracture area. One group was treated with pamidronate, the other group with placebo via the matrix. To investigate the volume and quality of the callus we used micro-CT (μCT) and histology after 14 and 28 days.Results: Our results show a positive influence of local applied pamidronate on callus volume. After 14 days an insignificant increase of callus volume in the treated animals was seen. 28 days after trauma the increase of callus volume in the treatment group was significantly higher in comparison to the control group. Osteonecrosis was not seen.Conclusions: Locally applied bisphosphonates increase the callus volume in fracture healing. [ABSTRACT FROM AUTHOR]

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF. [ABSTRACT FROM AUTHOR]

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates. We analyzed nuclear blebbing/TUNEL, sGAG content, immunohistochemistry, and the expression of COL1A1, COL2A1, COL10A1, SOX9, and ACAN. Post-injuriously, PC was associated with less cell death, increased COL2A1 expression, and decreased COL10A1 expression and, interestingly, the combination with Il-10 or Il-10 alone had no additional effects, except on COL10A1, which was most effectively decreased by the combination of PC and Il-10. The expression of COL2A1 or SOX9 was statistically not modulated by these substances. In contrast, in chondrocytes in ACI grafts the combination of PC and IL-10 had the most pronounced effects on all parameters except ACAN. Thus, using adjuvants such as PC and IL-10, preferably in combination, is a promising strategy for enhancing repair and graft maturation of autologous transplanted chondrocytes after cartilage injury. [ABSTRACT FROM AUTHOR]

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products. [ABSTRACT FROM AUTHOR]

A continuing challenge in cartilage tissue engineering for cartilage regeneration is the creation of a suitable synthetic microenvironment for chondrocytes and tissue regeneration. The aim of this study was to develop a highly tunable hybrid scaffold based on a silk fibroin matrix (SM) and a hyaluronic acid (HA) hydrogel. Human articular chondrocytes were embedded in a porous 3-dimensional SM, before infiltration with tyramine modified HA hydrogel. Scaffolds were cultured in chondropermissive medium with and without TGF-β1. Cell viability and cell distribution were assessed using CellTiter-Blue assay and Live/Dead staining. Chondrogenic marker expression was detected using qPCR. Biosynthesis of matrix compounds was analyzed by dimethylmethylene blue assay and immuno-histology. Differences in biomaterial stiffness and stress relaxation were characterized using a one-step unconfined compression test. Cell morphology was investigated by scanning electron microscopy. Hybrid scaffold revealed superior chondro-inductive and biomechanical properties compared to sole SM. The presence of HA and TGF-β1 increased chondrogenic marker gene expression and matrix deposition. Hybrid scaffolds offer cytocompatible and highly tunable properties as cell-carrier systems, as well as favorable biomechanical properties. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was in thoracolumbar fractures to assess the effectiveness of minimal invasive stabilisation compared to the open technique with regards to the change in kyphosis angle, the loss of reduction and length of hospital stay.Methods: The retrospective study consisted of 104 patients who received minimally invasive stabilisation or open stabilisation. Patients were between 15 and 86 years of age, had a thoracolumbar fracture and no neurological deficits. Kyphotic angle (Cobb angle) and loss of reduction was compared after minimal invasive and open stabilisation. The Cobb angle was evaluated directly post operatively, at 6 weeks, 3 months, 6 months and 12 months after surgery.Results: Evaluated patients who received the minimally invasive technique had a shorter surgical intervention time and a shorter hospital stay compared to patients who received the open technique. Kyphosis angle and loss of reduction showed no significant difference compared to open technique. There was also no significant difference between minimally invasive poly-axial and mono-axial stabilisation.Conclusion: In this study we provide evidence that MIS instrumentation in selected thoracolumbar fractures can effectively be used without significant differences in loss of reduction compared to open stabilisation. MIS can also sufficiently retain reduction as compared to traditional open techniques. The main advantages are reduced operation time and shorter hospital stay. [ABSTRACT FROM AUTHOR]