Extrusion-based 3D printing of osteoinductive scaffolds with a spongiosa-inspired structure.

Critical-sized bone defects resulting from trauma, inflammation, and tumor resections are individual in their size and shape. Implants for the treatment of such defects have to consider biomechanical and biomedical factors, as well as the individual conditions within the implantation site. In this context, 3D printing technologies offer new possibilities to design and produce patient-specific implants reflecting the outer shape and internal structure of the replaced bone tissue. The selection or modification of materials used in 3D printing enables the adaption of the implant, by enhancing the osteoinductive or biomechanical properties. In this study, scaffolds with bone spongiosa-inspired structure for extrusion-based 3D printing were generated. The computer aided design process resulted in an up scaled and simplified version of the bone spongiosa. To enhance the osteoinductive properties of the 3D printed construct, polycaprolactone (PCL) was combined with 20% (wt) calcium phosphate nano powder (CaP). The implants were designed in form of a ring structure and revealed an irregular and interconnected porous structure with a calculated porosity of 35.2% and a compression strength within the range of the natural cancellous bone. The implants were assessed in terms of biocompatibility and osteoinductivity using the osteosarcoma cell line MG63 and patient-derived mesenchymal stem cells in selected experiments. Cell growth and differentiation over 14 days were monitored using confocal laser scanning microscopy, scanning electron microscopy, deoxyribonucleic acid (DNA) quantification, gene expression analysis, and quantitative assessment of calcification. MG63 cells and human mesenchymal stem cells (hMSC) adhered to the printed implants and revealed a typical elongated morphology as indicated by microscopy. Using DNA quantification, no differences for PCL or PCL-CaP in the initial adhesion of MG63 cells were observed, while the PCL-based scaffolds favored cell proliferation in the early phases of culture up to 7 days. In contrast, on PCL-CaP, cell proliferation for MG63 cells was not evident, while data from PCR and the levels of calcification, or alkaline phosphatase activity, indicated osteogenic differentiation within the PCL-CaP constructs over time. For hMSC, the highest levels in the total calcium content were observed for the PCL-CaP constructs, thus underlining the osteoinductive properties.

Percutaneous thoraco-lumbar-sacral pedicle screw placement accuracy results from a multi-center, prospective clinical study using a skin marker-based optical navigation system.

STUDY DESIGN: Prospective multi-center study. OBJECTIVE: The study aimed to evaluate the accuracy of pedicle screw placement using a skin marker-based optical surgical navigation system for minimal invasive thoraco-lumbar-sacral pedicle screw placement. METHODS: The study was performed in a hybrid Operating Room with a video camera-based navigation system integrated in the imaging hardware. The patient was tracked with non-invasive skin markers while the instrument tracking was via an on-shaft optical marker pattern. The screw placement accuracy assessment was performed by three independent reviewers, using the Gertzbein grading. The screw placement time as well as the staff and patient radiation doses was also measured. RESULTS: In total, 211 screws in 39 patients were analyzed for screw placement accuracy. Of these 32.7% were in the thoracic region, 59.7% were in the lumbar region, and 7.6% were in the sacral region. An overall accuracy of 98.1% was achieved. No screws were deemed severely misplaced (Gertzbein grading 3). The average time for screw placement was 6 min and 25 secs (± 3 min 33 secs). The average operator radiation dose per subject was 40.3 µSv. The mean patient effective dose (ED) was 11.94 mSv. CONCLUSION: Skin marker-based ON can be used to achieve very accurate thoracolumbarsacral pedicle screw placements.

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.

Stimulation of human bone marrow mesenchymal stem cells by electromagnetic transduction therapy - EMTT.

Many different pulsed electromagnetic field (PEMF) devises have been clinically used to stimulate healing processes, but many procedures are still without supporting basic research data. The aim of this study was to investigate a new modified pulsed electromagnetic field therapy: electromagnetic transduction therapy (EMTT). EMTT is technically based on high-intensive PEMFs with a magnetic field strength between 80 and 150 mT. The effect of EMTT for a 10-min session three times a week on human bone marrow mesenchymal stem cells (MSCs) was evaluated by assessing cell viability, gene expression of bone regenerative factors and VEGF-A (vascular endothelial growth factor) secretion after 7 and 14 days of treatment. No negative or toxic effects of EMTT on MSCs in vitro were observed in the applied test frame. The VEGF-ELISA at day 7 of EMTT treatment with 80 mT showed a significant higher VEGF concentration compared to untreated control group. In conclusion, high-intensive electromagnetic impulses showed no harmful effects on MSC cultures in our study. The enhancement of the proangiogenic factor VEGF in MSCs on day 7 indicates a substantial role in cell-stimulating effect of EMTT. Further in vitro and in vivo studies should differentiate specific stimulating and regenerating effects of EMTT impulses in soft tissue engineering. Specific electromagnetic characteristics have to be determined to optimize electromagnetic treatment options in orthopedic surgery and traumatology and soft tissue treatment options.

Graphene Oxide Framework Structures and Coatings: Impact on Cell Adhesion and Pre-Vascularization Processes for Bone Grafts.

Graphene oxide (GO) is a promising material for bone tissue engineering, but the validation of its molecular biological effects, especially in the context of clinically applied materials, is still limited. In this study, we compare the effects of graphene oxide framework structures (F-GO) and reduced graphene oxide-based framework structures (F-rGO) as scaffold material with a special focus on vascularization associated processes and mechanisms in the bone. Highly porous networks of zinc oxide tetrapods serving as sacrificial templates were used to create F-GO and F-rGO with porosities >99% consisting of hollow interconnected microtubes. Framework materials were seeded with human mesenchymal stem cells (MSC), and the cell response was evaluated by confocal laser scanning microscopy (CLSM), deoxyribonucleic acid (DNA) quantification, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and alkaline phosphatase activity (ALP) to define their impact on cellular adhesion, osteogenic differentiation, and secretion of vascular growth factors. F-GO based scaffolds improved adhesion and growth of MSC as indicated by CLSM and DNA quantification. Further, F-GO showed a better vascular endothelial growth factor (VEGF) binding capacity and improved cell growth as well as the formation of microvascular capillary-like structures in co-cultures with outgrowth endothelial cells (OEC). These results clearly favored non-reduced graphene oxide in the form of F-GO for bone regeneration applications. To study GO in the context of a clinically used implant material, we coated a commercially available xenograft (Bio-Oss® block) with GO and compared the growth of MSC in monoculture and in coculture with OEC to the native scaffold. We observed a significantly improved growth of MSC and formation of prevascular structures on coated Bio-Oss®, again associated with a higher VEGF binding capacity. We conclude that graphene oxide coating of this clinically used, but highly debiologized bone graft improves MSC cell adhesion and vascularization.

In vivo biocompatibility evaluation of 3D-printed nickel-titanium fabricated by selective laser melting.

Nickel-titanium (NiTi) belongs to the group of shape-memory alloys (SMAs), which are characterized by flexibility and reversible deformability. Advanced techniques in 3D printing by selective laser-melting (SLM) process allow the manufacturing of complex patient-specific implants from SMAs. Osteosynthesis materials made of NiTi could be used for minimally invasive surgical approaches in oral- and maxillofacial surgery. However, the in vivo biocompatibility has not yet been fully investigated, especially in load-sharing and load-bearing implants. The aim of this study was to evaluate the in vivo biocompatibility of SLM-produced NiTi for intraosseous and subperiosteal applications. Test specimens were implanted into the frontonasal bone of ten miniature pigs. To assess peri-implant bone metabolism, fluorescent dye was administered after 2, 4, 6, 10, 12, and 14 weeks intraperitoneally. Specimens and the surrounding tissues were harvested after 8 and 16 weeks for histological analysis. While the NiTi implants presented a higher bone-to-implant contact ratio (BIC) after 8 than after 16 weeks (43.3 vs. 40.3%), the titanium implants had a significantly higher BIC after 16 weeks (33.6 vs. 67.7%). Histologically, no signs of peri-implant inflammation or foreign-body reaction were detectable. With respect to this preliminary study design, 3D-printed NiTi shows sufficient biocompatibility for intraosseous and subperiosteal implant placement.

Does the time of the day affect multiple trauma care in hospitals? A retrospective analysis of data from the TraumaRegister DGU®.

BACKGROUND: Optimal multiple trauma care should be continuously provided during the day and night. Several studies have demonstrated worse outcomes and higher mortality in patients admitted at night. This study involved the analysis of a population of multiple trauma patients admitted at night and a comparison of various indicators of the quality of care at different admission times. METHODS: Data from 58,939 multiple trauma patients from 2007 to 2017 were analyzed retrospectively. All data were obtained from TraumaRegister DGU®. Patients were grouped by the time of their admission to the trauma center (6.00 am-11.59 am (morning), 12.00 pm-5.59 pm (afternoon), 6.00 pm-11.59 pm (evening), 0.00 am-5.59 am (night)). Incidences, patient demographics, injury patterns, trauma center levels and trauma care times and outcomes were evaluated. RESULTS: Fewer patients were admitted during the night (6.00 pm-11.59 pm: 18.8% of the patients, 0.00-5.59 am: 4.6% of the patients) than during the day. Patients who arrived between 0.00 am-5.59 am were younger (49.4 ± 22.8 years) and had a higher injury severity score (ISS) (21.4 ± 11.5) and lower Glasgow Coma Scale (GCS) score (11.6 ± 4.4) than those admitted during the day (12.00 pm-05.59 pm; age: 55.3 ± 21.6 years, ISS: 20.6 ± 11.4, GCS: 12.6 ± 4.0). Time in the trauma department and time to an emergency operation were only marginally different. Time to imaging was slightly prolonged during the night (0.00 am-5.59 am: X-ray 16.2 ± 19.8 min; CT scan 24.3 ± 18.1 min versus 12.00 pm- 5.59 pm: X-ray 15.4 ± 19.7 min; CT scan 22.5 ± 17.8 min), but the delay did not affect the outcome. The outcome was also not affected by level of the trauma center. There was no relevant difference in the Revised Injury Severity Classification II (RISC II) score or mortality rate between patients admitted during the day and at night. There were no differences in RISC II scores or mortality rates according to time period. Admission at night was not a predictor of a higher mortality rate. CONCLUSION: The patient population and injury severity vary between the day and night with regard to age, injury pattern and trauma mechanism. Despite the differences in these factors, arrival at night did not have a negative effect on the outcome.

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.

Accuracy of augmented reality surgical navigation for minimally invasive pedicle screw insertion in the thoracic and lumbar spine with a new tracking device.

BACKGROUND CONTEXT: Minimally invasive approaches are increasingly used in spine surgery. The purpose of navigation systems is to guide the surgeon and to reduce intraoperative x-ray exposure. PURPOSE: This study aimed to determine the feasibility and clinical accuracy of a navigation technology based on augmented reality surgical navigation (ARSN) for minimally invasive thoracic and lumbar pedicle screw instrumentation compared with standard fluoroscopy-guided minimally invasive technique. STUDY DESIGN/SETTING: Cadaveric laboratory study. METHODS: ARSN was installed in a hybrid operating room, consisting of a flat panel detector c-arm with two dimensional/three dimensional imaging capabilities and four integrated cameras in its frame. The surface-referenced navigation device does not require a bony reference but uses video cameras and optical markers applied to the patient's skin for tracking. In four cadavers, a total of 136 pedicle screws were inserted in thoracic and lumbar vertebrae. The accuracy was assessed by three independent raters in postoperative conventional computed tomography. RESULTS: The overall accuracy of ARSN was 94% compared with an accuracy of 88% for fluoroscopy. The difference was not statistically significant. In the thoracic region, accuracy with ARSN was 92% compared with 83% with fluoroscopy. With fluoroscopy, unsafe screws were observed in three normal cadavers and one with scoliosis. Using ARSN, unsafe screws were only observed in the scoliotic spine. No significant difference in the median of time for K-wire placement was recorded. As no intraoperative fluoroscopy was necessary in ARSN, the performing surgeon was not exposed to radiation. CONCLUSIONS: In this limited cadaveric study minimally invasive screw placement using ARSN was demonstrated to be feasible and as accurate as fluoroscopy. It did not require any additional navigation time or use of any intraoperative x-ray imaging, thereby potentially permitting surgery in a protective lead garment-free environment. A well-powered clinical study is needed to demonstrate a significant difference in the accuracy between the two methods. CLINICAL SIGNIFICANCE: ARSN offers real-time imaging of planned insertion paths, instrument tracking, and overlay of three dimensional bony anatomy and surface topography. The referencing procedure, by optical recognition of several skin markers is easy and does not require a solid bony reference as necessary for conventional navigation which saves time. Additionally, ARSN may foster the reduction of intraoperative x-ray exposure to spinal surgeons.

Evaluation of bone allograft processing methods: Impact on decellularization efficacy, biocompatibility and mesenchymal stem cell functionality.

In an ever-aging society the demand for bone-defect filling grafts continues to gain in importance. While autologous grafting still prevails as the gold standard, allografts and xenografts present viable alternatives with promising results. Physiochemical properties of a graft strongly depend on the processing method such as the decellularization protocol. In addition, the physiochemical characteristics are critical factors for a successful integration of the graft after the implantation and might influence mesenchymal stem cell function in therapeutic approaches combining grafts and autologous mesenchymal stem cells (MSCs). Several decellularization methods have been proposed, however it still remains unclear which method results in favorable physiochemical properties or might be preferred in stem cell applications. In the first part of this study we compared two decellularization approaches resulting in chemically processed allografts (CPAs) or sonication-based processed allografts (SPAs). Each decellularization approach was compared for its decellularization efficacy and its influence on the grafts' surface texture and composition. In the second part of this study biocompatibility of grafts was assessed by testing the effect of extraction medium on MSC viability and comparing them to commercially available allografts and xenografts. Additionally, grafts' performance in terms of MSC functionality was assessed by reseeding with MSCs pre-differentiated in osteogenic medium and determining cell adhesion, proliferation, as well as alkaline phosphatase (ALP) activity and the degree of mineralization. In summary, results indicate a more effective decellularization for the SPA approach in comparison to the CPA approach. Even though SPA extracts induced a decrease in MSC viability, MSC performance after reseeding was comparable to commercially available grafts based on DNA quantification, alkaline phosphatase activity and quantification of mineralization. Commercial Tutoplast allografts showed overall the best effects on MSC functionality as indicated by extraction biocompatibility testing as well as by comparing proliferation and osteogenic differentiation.

Missed foot fractures in multiple trauma patients.

BACKGROUND: Missed or underestimated injuries are one of the central problems in trauma care. Foot injuries can easily be missed because they lay beyond the regularly screened field of a trauma computer tomography scan (CT scan). During primary and secondary survey a careful examination of the extremities often becomes of secondary interest in the severely injured patient. METHODS: Thirty-four thousand ninety-one multiple trauma patients of the TraumaRegister DGU® were evaluated from 2002 to 2014. We differentiated between patients with foot injuries, patients with missed foot injuries and patients without foot injuries. Included were ankle fractures, calcaneus fractures, talus fractures, metatarsal fractures, toe fractures, amputation, soft tissue injuries and/or ligamentous injuries. RESULTS: Summarized evaluation of 34,091 trauma patients showed a share of 2532 patients with foot injuries. Time of diagnosis was documented in 2199 cases. 2055 patients had early diagnosed foot injuries and 144 patients had initially missed foot injuries. Missed foot injuries were especially found in patients with car accidents or fall from ≥3 m. Patients with higher Abbreviated Injury Scale (AIS) or lower Glasgow Coma Scale (GCS) were not significantly more affected by missed foot injuries. Missing foot injuries was also not caused by injury severity or higher age. CONCLUSIONS: Our data highlights the need of careful evaluation of the feet during primary and secondary survey particularly when a tibia or femur fracture is diagnosed. Special attention should be turned to patients after car accidents or fall from great height. Suicide victims also need major attention. Patients with early operations also need careful examination and tertiary survey is highly recommended.

Electromagnetic transduction therapy and shockwave therapy in 86 patients with rotator cuff tendinopathy: A prospective randomized controlled trial.

Rotator cuff (RC) tendinopathy is the most common cause of shoulder pain. The effectiveness of electromagnetic transduction therapy (EMTT), a high energetic pulsed electromagnetic field therapy in this field has not been tested yet in combination with extracorporeal shock wave therapy (ESWT). A total of 86 patients with RC tendinopathy were randomized to undergo three sessions of ESWT in combination with 8 sessions of EMTT or sham-EMTT. Both intervention groups experienced significant and clinical relevant decrease of pain at all follow-up visits, and the functionality of the shoulder evaluated by the Constant Murley score increased significantly as well. The combination of EMTT + ESWT produced significantly greater pain reduction in the visual analogue scale compared to ESWT with sham-EMTT after 24 weeks, during which the Constant Murley score improved significantly when the combination of ESWT and EMTT was employed. In patients with RC tendinopathy, electromagnetic transduction therapy combined with extracorporeal shock wave therapy significantly improves pain and function compared to ESWT with sham-EMTT.

Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF®) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation.

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes.

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.

Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes.

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.

Electromagnetic transduction therapy in non-specific low back pain: A prospective randomised controlled trial.

OBJECTIVES: A prospective randomised controlled trial to investigate the efficacy of electromagnetic transduction therapy (EMTT) for treatment of patients with non-specific low back pain. DESIGN: Two groups with non-specific low back pain were either treated with conventional therapy alone over 6 weeks or in combination with 8 sessions of EMTT. RESULTS: In both intervention groups the low back pain related pain and the degree of disability decreased significantly at follow-up visits. Combination of EMTT and conventional therapy proved significant superior to conventional therapy alone. CONCLUSION: EMTT is a promising treatment in patients with non-specific low back pain.

Platelet-released growth factors induce psoriasin in keratinocytes: Implications for the cutaneous barrier.

Millions of patients around the world suffer minor or major extremity amputation due to progressive wound healing complications of chronic or infected wounds, the therapy of which remains a challenge. One emerging therapeutic option for the treatment of these complicated wounds is the local application of an autologous thrombocytes concentrate lysate (e.g. platelet-released growth factors ((PRGF)) or Vivostat PRF®) that contains a multitude of chemokines, cytokines and growth factors and is therefore supposed to stimulate the complex wound healing process. Although PRGF and Vivostat PRF® are already used successfully to support healing of chronic, hard-to-heal and infected wounds the underlying molecular mechanisms are not well understood. Psoriasin, also termed S100A7, is a multifunctional antimicrobial protein expressed in keratinocytes and is involved in various processes such as wound-healing, angiogenesis, innate immunity and immune-modulation. In this study, we investigated the influence of PRGF on psoriasin expression in human primary keratinocytes in vitro and the influence of Vivostat PRF® on psoriasin expression in experimentally generated skin wounds in vivo. PRGF treatment of primary keratinocytes caused a significant concentration- and time-dependent increase of psoriasin gene and protein expression in vitro that were partially mediated by the epidermal growth factor receptor (EGFR) and the interleukin-6 receptor (IL-6R). In accordance with these cell culture data, Vivostat PRF® induced a significant psoriasin gene and protein expression when applied to artificially generated skin wounds in vivo. The observed psoriasin induction in keratinocytes may contribute to the wound healing-promoting effects of therapeutically used thrombocyte concentrate lysates.