Isometry of anteromedial reconstructions mimicking the deep medial collateral ligament depends on the femoral insertion.

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.

Antibacterial properties of marine algae incorporated polylactide acid membranes as an alternative to clinically applied different collagen membranes.

The reconstruction of bony defects in the alveolar crest poses challenges in dental practice. Guided tissue regeneration (GTR) and guided bone regeneration (GBR) procedures utilize barriers to promote bone regeneration and prevent epithelial growth. This study focuses on evaluating the antibacterial properties of marine algae-polylactic acid (PLA) composite membranes compared to commercially available collagen membranes. Marine algae (Corallina elongata, Galaxaura oblongata, Cystoseira compressa, Saragassum vulgare, and Stypopodium schimperi) were processed into powders and blended with PLA to fabricate composite membranes. Cytocompatibility assays using human periodontal ligament fibroblasts (n = 3) were performed to evaluate biocompatibility. Antibacterial effects were assessed through colony-forming units (CFU) and scanning electron microscopy (SEM) analysis of bacterial colonization on the membranes. The cytocompatibility assays demonstrated suitable biocompatibility of all marine algae-PLA composite membranes with human periodontal ligament fibroblasts. Antibacterial assessment revealed that Sargassum vulgare-PLA membranes exhibited the highest resistance to bacterial colonization, followed by Galaxaura oblongata-PLA and Cystoseira compressa-PLA membranes. SEM analysis confirmed these findings and revealed smooth surface textures for the marine algae-PLA membranes compared to the fibrous and porous structures of collagen membranes. Marine algae-PLA composite membranes show promising antibacterial properties and cytocompatibility for guided bone and tissue regeneration applications. Sargassum vulgare-PLA membranes demonstrated the highest resistance against bacterial colonization. These findings suggest that marine algae-PLA composite membranes could serve as effective biomaterials for infection control and tissue regeneration. Further in vivo validation and investigation of biodegradation properties are necessary to explore their clinical potential.

Coaching as a growth- or security-oriented process-How regulatory fit increases coaching success.

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.

[Multiligament instabilities of the knee in sports injuries : An update of the Hamburg concept]. / Multiligamentäre Instabilitäten des Kniegelenkes bei Sportverletzungen : Ein Update zum "Hamburger Konzept".

BACKGROUND: Knee dislocation (KD) is a rare but severe injury of the knee joint, with a high rate of concomitant neurovascular injuries. The severity of the ligamentous injury, which is classified according to the Schenck classification, the mechanism of injury, concomitant injuries and individual factors determine the treatment strategy in KD. TREATMENT STRATEGY: Furthermore, a clear differentiation between high-velocity (HV) and low-velocity (LV) injuries is necessary. Generally, surgical treatment within 7-10 days should be aspired. Herein, the one-stage hybrid treatment using augmented ligament sutures (ligament bracing) in combination with primary ligament reconstruction (posterolateral and ACL) leads to very good functional results in the mid-term. Ultra-low-velocity (ULV) dislocations and those with concomitant peroneal lesions require a modified approach, due to a limited prognosis. During rehabilitation, the individual progress must be closely monitored and follow an early functional approach. In approximately 20% of all cases, early arthroscopic arthrolysis shows a high success rate.

Comparison of different intraoperative reduction monitoring methods in a cadaveric intraarticular calcaneal fracture model: 3D scan vs arthroscopy vs nanoscopy.

AIMS: Visualization of the subtalar joint surface in surgical management of calcaneal factures remains a big challenge and anatomic reduction of the articular surface is essential for a good clinical outcome. We hypothesize that video-assistance can provide superior fracture reduction compared to fluoroscopy and that nanoscopy (NSC) achieves more extensive visualization compared to fracturoscopy (FSC). METHODS: Ten human cadaveric feet with artificially pre-fractured intraarticular calcaneal fractures with involvement of the posterior facet were treated via a minimal invasive subtalar approach. After initial control of reduction by 2D fluoroscopy, the reduction was further analyzed intraoperatively by FSC and NSC. 3D Scan served as gold standard control of reduction. Need of revision of reduction after the different visualization techniques was recorded and the extent of visualization of the subtalar joint surface in the medio-lateral dimension was compared for FSC and NSC. To quantify access and visualization of the medial and posterior facet, a depth gauge was used to measure from laterally at the clinically widest portion of the calcaneus targeted to the sustentaculum tali. The distance in millimetres was referred to the complete medio-lateral distance seen on paracoronal CT at the widest portion of the calcaneus. RESULTS: Fracture analysis in preoperative CT-scans according to Sanders classification revealed four type IC, two IIA, three IIC and one IIIAC fractures. Mean visualization of the medial and posterior facet was significantly improved with NSC (30.4 ± 3.78 mm) compared to FSC (23.6 ± 6.17 mm) (p = 0.008). An imperfect reduction requiring revision was more often required with NSC compared to FSC. Insufficient reduction using video-assistance was found in two cases. CONCLUSION: In order to optimize subtalar joint reduction and congruency, video-assisted techniques, especially NSC, provide superior visualization and thus can improve reduction in the surgical treatment of intraarticular calcaneal fractures.

Comparison of Onlay Anchor Fixation Versus Transosseous Fixation for Lateral Extra-articular Tenodesis During Revision ACL Reconstruction.

Background: There is evidence on the clinical effectiveness of the Lemaire technique for lateral extra-articular tenodesis (LET) in patients undergoing revision anterior cruciate ligament reconstruction (ACLR), but the best fixation technique is unknown. Purpose: To compare the clinical outcomes of 2 fixation techniques after revision ACLR: (1) onlay anchor fixation, which would avoid tunnel conflict and physis injury, and (2) transosseous tightening and interference screw fixation. Pain at the area of LET fixation was also assessed. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective 2-center study of patients with first-time revision ACLR and either LET with anchor fixation (aLET) with a 2.4-mm suture anchor or LET with transosseous fixation (tLET). Outcomes at minimum 12-month follow-up were assessed with the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, visual analog scale for pain at the LET fixation area, Tegner score, and anterior tibial translation (ATT). A subgroup analysis within the aLET group investigated passing the graft over or under the lateral collateral ligament (LCL). Results: In total, 52 patients were included (26 patients in each group); the mean ± SD follow-up was 13.7 ± 3.4 months. No statistically significant differences were detected between the groups with respect to patient-reported outcome scores, clinical examination, or instrumented testing (side-to-side difference in ATT at 30° of flexion; aLET, 1.5 ± 2.5 mm; tLET, 1.6 ± 1.7 mm). Clinical failure was detected in 1 patient with aLET and none with tLET. Subgroup analysis revealed a small, nonsignificant flexion deficit in knees in which the iliotibial band strand was passed under (n = 42) or over (n = 10) the LCL. No clinically relevant tenderness was detected at the area of LET fixation in any group (aLET, 0.6 ± 1.3; tLET, 0.9 ± 1.7; over the LCL, 0.2 ± 0.6; under the LCL, 0.9 ± 1.6). Conclusion: Onlay anchor fixation and transosseous fixation of the LET were equivalent with respect to outcome scores and instrumented ATT testing. Clinically, there were minor differences in passage of the LET graft over or under the LCL.

In Vitro Comparison of 2 Clinically Applied Biomaterials for Autologous Chondrocyte Implantation: Injectable Hydrogel Versus Collagen Scaffold.

OBJECTIVE: In autologous chondrocyte implantation (ACI), there is no consensus about used bioscaffolds. The aim of this study was to perform an in vitro comparative analysis of 2 clinically applied biomaterials for cartilage lesion treatment. DESIGN: Monolayer expanded human chondrocytes (n = 6) were embedded in a collagen scaffold (CS) and a hyaluronic acid-based hydrogel (HA). Cells were cultured in chondropermissive medium supplemented with and without interleukin-10 (IL-10) and bone morphogenetic protein-2 (BMP-2). Gene expression of chondrogenic markers (COL1A1, COL2A1, COL10A1, ACAN, SOX9) was detected via quantitative real-time-polymerase chain reaction (RT-qPCR). Biosynthesis of matrix compounds, cell viability, morphology as well as migration from surrounding native bovine cartilage into cell-free scaffolds were analyzed histologically. Adhesion of the material to adjacent cartilage was investigated by a custom-made push-out test. RESULTS: The shift of COL1/2 ratio toward COL2A1 was more pronounced in HA, and cells displayed a more spherical morphology compared with CS. BMP-2 and IL-10 significantly increased COL2A1, SOX9, and ACAN expression, which was paralleled by enhanced staining of glycosaminoglycans (GAGs) and type 2 collagen in histological sections of CS and HA. COL10A1 was not significantly expressed in HA and CS. Better interfacial integration and enhanced cell invasion was observed in CS. Push-out tests using CS showed higher bonding strength to native cartilage. CONCLUSION: HA-based hydrogel revealed a more chondrocyte-like phenotype but only allowed limited cell invasion, whereas CS were advantageous in terms of cellular invasion and interfacial adhesion. These differences may be clinically relevant when treating cartilaginous or osteochondral defects.

Nanoscopy and an extended lateral approach can improve the management of latero-central segments in tibial plateau fractures: a cadaveric study.

INTRODUCTION: The objective of this investigation was to compare different techniques to improve visualization and reduction in tibial plateau fractures involving the central lateral segments. METHODS: Matched pairs of pre-fractured cadaveric tibial plateau fractures that include the central lateral segments were treated by either an anterolateral approach (supine) or PL approach (prone). Reduction was stepwise extended by additional fracturoscopy (FS), nanoscopy (NS) and lastly by epicondyle osteotomy (ECO). Reduction was analyzed by 3D scan and visualization of the lateral plateau was quantified. RESULTS: Ten specimens (3 pairs 41B3.1, 2 pairs 41C3.3) were analyzed. Fracture steps involving the antero-latero-central (ALC) segment were insufficiently reduced after fluoroscopy using both approaches (AL 2.2 ± 1.2 mm vs PL 2.2 ± 1.0 mm, p 0.95). Additional NS and ECO achieved optimized fracture reduction in the ALC segment (NS AL 1.6 ± 1.3 mm vs PL 0.8 ± 0.9 mm, p 0.32). NS provided visualization of the entire lateral plateau (PL 102.9% ± 7.4, AL 108.8 ± 19.2%), while fracturoscopy only allowed visualization of the ALL segment and partially of PLL and ALC segments (PL 22.0 ± 23.4%, AL 29.7 ± 18.3%). CONCLUSION: Optimized reduction of tibial head fractures with involvement of latero-central segments requires additional video-assisted reduction or extended approaches. Nanoscopy helps visualizing of the entire lateral plateau, when compared to fracturoscopy and may become a valuable reduction aid.

Anterolateral versus modified posterolateral approach for tibial plateau fractures with involvement of the posterior column: a cadaveric study.

INTRODUCTION: The aim of this study was to compare the reduction quality of the anterolateral (AL) and modified posterolateral approach (PL) in lateral tibial plateau fractures involving the posterior column and central segments. METHODS: Matched pairs of pre-fractured cadaveric tibial plateau fractures were treated by either AL approach (supine position) or PL approach (prone position). Reduction was controlled by fluoroscopy and evaluated as satisfying or unacceptable. Afterwards, the reduction was examined by 3D scan. RESULTS: 10 specimens (3 pairs 41B3.1, 2 pairs 41C3.3) were evaluated. PL approach achieved significantly (p 0.00472) better fracture reduction results (0.4 ± 0.7 mm) of the posterior column compared to the AL group (2.1 ± 1.4 mm). Fracture steps involving the central area of the lateral plateau were insufficiently reduced after fluoroscopy using both approaches. CONCLUSION: Optimal reduction of displaced tibial plateau fractures involving the posterolateral column necessitates a posterior approach, which can be conducted in prone or lateral positioning. The anterolateral approach is indicated in fractures with minor displacement of the posterolateral rim but fracture extension in the latero-central segments. In these cases, an additional video-assisted reduction or extended approaches are helpful.

Retrospective Mid-Term Follow-Up of Posttraumatic and Iatrogenic Neurovascular Complications in Surgically Treated Paediatric Patients with Distal Humerus Fracture.

BACKGROUND: The purpose of the study was to investigate and describe neurovascular complications and mid-term clinical outcomes of operatively managed fractures of the distal humerus in a paediatric population. Neurovascular injuries are common in these fractures, but reports about their implications for mid-term clinical outcomes is sparse. METHODS: A single-centre retrospective study was conducted at a university teaching hospital investigating paediatric patients who underwent operative management of a distal humerus fracture between 2014 and 2018. Patient demographics, fracture classification, pre-, peri- and postoperative neurovascular complications were investigated. Mid-term follow up clinical examination and functional scoring using QuickDASH, the Broberg and Morrey Score (BMS), the Mayo Elbow Performance Score (MEPS) and the Numeric Rating Scale were performed. RESULTS: A total of 84 patients were identified, of which 34 met the inclusion criteria and were available for follow-up clinical examination. The average time to follow-up was 150 weeks (1049.44 days ± 448.54). Ten primary traumatic neurovascular complications were identified, the majority of which involved the median nerve. Primary traumatic dissection of the brachial artery was recorded in three patients. Secondary iatrogenic nerve injury was documented in five patients after previously normal clinical examination. At follow-up, the average QuickDASH score was 3.0 ± 4.3, BMS was 98.6 ± 3.4 and MEPS was 97.1 ± 3.3 points. CONCLUSIONS: The mid-term clinical outcome following surgical management of distal humerus fractures is excellent. There is, however, a considerable frequency of both primary and secondary neurovascular complications, which must be considered when opting to treat these injuries surgically.

The Control of Anteromedial Rotatory Instability Is Improved With Combined Flat sMCL and Anteromedial Reconstruction.

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.

Platelet-Released Growth Factors Influence Wound Healing-Associated Genes in Human Keratinocytes and Ex Vivo Skin Explants.

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.

Arthroscopic anatomy of the posterolateral corner of the knee: anatomic relations and arthroscopic approaches.

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.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro.

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.

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

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.

Silk Fiber-Reinforced Hyaluronic Acid-Based Hydrogel for Cartilage Tissue Engineering.

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-ß1. 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-ß1 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.

Missed hand and forearm injuries in multiple trauma patients: An analysis from the TraumaRegister DGU®.

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.

An Ex Vivo Bone Defect Model to Evaluate Bone Substitutes and Associated Bone Regeneration Processes.

The increased incidence of bone defects, especially in cases of comminuted fractures or bone tumor resections demands suitable bone grafts and substitutes. The aim of this study was to establish an ex vivo bone defect model to evaluate new bone substitutes and associated repair processes under controlled conditions. Femoral heads derived from patients undergoing total hip replacement were cut into cylinders (20 mm diameter, 7 mm height). A central bone defect (6 mm diameter, 5 mm depth) was inserted centrally. The bone slides were cultured for 28 days and viability was evaluated by lactate dehydrogenase and alkaline phosphatase assay, and Calcein-AM viability staining and DNA quantification. Data revealed the viability of the bone tissue over the tested time period of 28 days, and an increase in cell numbers implicating active cell proliferation processes in the sections. To analyze the bone regeneration potential of this model in combination with a bone replacement material, we injected a collagen-type 1 hydrogel into the central defect. Cellular ingrowth into the gel was evaluated by microscopy and DNA quantification at different time points demonstrating an increase of cells in the defect over time. Finally, gene expression of osteogenic markers indicated an osteoblastic phenotype of the cells in the defect. In summary, the ex vivo bone defect model remains viable and shows active bone repair processes over 28 days. Additional advantages include high reproducibility, manageable costs, and a native bone-implant interface supporting the evaluation of bone substitute materials and associated regeneration processes. Impact statement Testing of new implant materials and bone repair strategies up to date rely mainly on in vivo and in vitro investigation models providing different pros and cons. In this study we established a novel human ex vivo bone defect model with a proven vitality of at least 28 days. The model provides a native bone implant interface and is designed to monitor cell invasion into a critically sized defect filled with the potential implant material. Furthermore, associated repair processes can be documented on the cell and molecular level, including additional advantages such as high reproducibility and manageable costs.

Articular Joint-Simulating Mechanical Load Activates Endogenous TGF-ß in a Highly Cellularized Bioadhesive Hydrogel for Cartilage Repair.

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-ß1). 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-ß1 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-ß1 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.