Blood Pressure Variability and Plasma Biomarkers of Neuronal Injury and Alzheimer's Disease: A Clinic-Based Study of Patients with Diseases Along the Heart-Brain Axis.

 Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and orthostatic hypotension in 518 participants with vascular cognitive impairment, carotid occlusive disease, heart failure, or reference participants. We determined cross-sectional associations between BPV indices and plasma biomarkers of neuronal injury (neurofilament light chain) and Alzheimer's disease (phosphorylated-tau-181 and Aß42/Aß40). None of the BPV indices were significantly associated with any of the biomarkers. Hence, in patients with diseases along the heart-brain axis, we found no evidence for an association between BPV and selected markers of neuronal injury or Alzheimer's disease.

[Large Language Models for Rapid Simplification of Quality Assurance Data Input: Field Trial with Real Data in the Context of Tumour Documentation in Urology]. / Large Language Modelle zur schnellen Vereinfachung der Eingabe von Qualitätssicherungsdaten: Performance-Test mit Echtdaten am Beispiel der Tumordokumentation in der Urologie.

INTRODUCTION: Large Language Models (LLMs) such as ChatGPT have rapidly brought the application of artificial intelligence into widespread use. Among many different use cases for text generation and processing, one application is the extraction of data from existing documents and conversations for simplified and automated form-filling. OBJECTIVE: In the field of quality assurance and documentation of cancer diseases, there is currently a significant workload involved in transferring data under various aspects into slightly varying formats and applying interpretations such as the TNM classification of tumours. However, there is a lack of trials with real data to assess the applicability of LLM-supported processes in this area, which would enable an evaluation of efficiency and practicality. This study aims to implement and assess such a trial. METHODOLOGY: A trial was conducted with N=153 privacy-compliant and ethics committee-cleared medical reports from 25 patients. Using the publicly available version of ChatGPT 4.0, an automated script was used to extract the date of initial diagnosis and common tumor classifications. The results were then individually checked for accuracy. Based on this, the utility of a simple system for guided support in tasks related to tumour documentation was assessed. Additionally, the approach was evaluated in terms of operational costs for the model and its applicability. RESULTS: In summary, the study concludes that the use of generative AI in this field is promising and suitable as a tool even in an untrained state. In a simplified calculation, costs of 35 cents are offset by a value creation of 61,54 euros. However, it also becomes clear that AI can only act in a supportive role, and the correct integration with pre-made specific prompts and tools into the workflow is crucial for a relevant performance. CONCLUSION: The use of generative AI in the context of search, transfer, and interpretation tasks in the creation of tumor documentation is a promising approach. However, its implementation in practical applications must be closely monitored, and the optimal interaction between man and machine should continue to be evaluated and must be accompanied by tools and task-specific prompts.

Routine 6-Week Outpatient Radiography and Visit in Patients with Conservatively Treated Multiple Rib Fractures: Valuable or a Waste of Resources?

Background: This study investigated the incidence and clinical consequences of abnormal radiological and clinical findings during routinely performed 6-week outpatient visits in patients treated conservatively for multiple (3 or more) rib fractures. Methods: A retrospective analysis was conducted among patients with multiple rib fractures treated conservatively between 2018 and 2021 (Opvent database). The primary outcome was the incidence of abnormalities on chest X-ray (CXR) and their clinical consequences, which were categorized as requiring intervention or additional clinical/radiological examination. The secondary focus was the incidence of deviation from standard treatment in response to the findings (clinical or radiological) at the routine 6-week outpatient visit. Results: In total, 364 patients were included, of whom 246 had a 6-week visit with CXR. The median age was 57 years (interquartile range, 46-70 years) and the median Injury Severity Score was 17 (interquartile range, 13-22). Forty-six abnormalities (18.7%) were found on CXR. These abnormalities resulted in additional outpatient visits in 4 patients (1.5%) and in chest drain insertion in 2 (0.8%). Only 2 patients (0.8%) with an abnormality on CXR presented without symptoms. None of the 118 patients who had visits without CXR experienced problems. Conclusion: Routine 6-week outpatient visits for patients with conservatively treated multiple rib fractures infrequently revealed abnormalities requiring treatment modifications. It may be questioned whether the 6-week outpatient visit is even necessary. Instead, a more targeted approach could be adopted, providing follow-up to high-risk or high-demand patients only, or offering guidance on recognizing warning signs and providing aftercare through a smartphone application.

Using Rapid Prototyping to Develop a Cell-Based Platform with Electrical Impedance Sensor Membranes for In Vitro RPMI2650 Nasal Nanotoxicology Monitoring.

Due to advances in additive manufacturing and prototyping, affordable and rapid microfluidic sensor-integrated assays can be fabricated using additive manufacturing, xurography and electrode shadow masking to create versatile platform technologies aimed toward qualitative assessment of acute cytotoxic or cytolytic events using stand-alone biochip platforms in the context of environmental risk assessment. In the current study, we established a nasal mucosa biosensing platform using RPMI2650 mucosa cells inside a membrane-integrated impedance-sensing biochip using exclusively rapid prototyping technologies. In a final proof-of-concept, we applied this biosensing platform to create human cell models of nasal mucosa for monitoring the acute cytotoxic effect of zinc oxide reference nanoparticles. Our data generated with the biochip platform successfully monitored the acute toxicity and cytolytic activity of 6 mM zinc oxide nanoparticles, which was non-invasively monitored as a negative impedance slope on nasal epithelial models, demonstrating the feasibility of rapid prototyping technologies such as additive manufacturing and xurography for cell-based platform development.

Does plate position influence the outcome in midshaft clavicular fractures? A multicenter analysis.

PURPOSE: To date, it remains unclear whether superior or anterior plating is the best option for treating midshaft clavicular fractures. The aim of this study was to compare both techniques with regard to the incidence of implant removal due to implant irritation, risk of complications, time to union, and function. METHODS: In this retrospective cohort study, all midshaft clavicular fractures treated operatively between 2017 and 2020 in two hospitals in Switzerland were analyzed. The participating hospitals differed with regard to their standard practice; one offered superior plating only, while the other predominantly employed an anterior plate. The primary outcome was the incidence of implant removal for irritation. Secondary outcomes were time to union, complications, re-interventions, and range of motion during the follow-up period of at least 6 months. RESULTS: In total, 168 patients were included in the study of which 81 (48%) received anterior plating and 87 (52%) superior plating. The overall mean age was 45 years (SD 16). There was no significant difference between anterior and superior plating with regard to implant removal (58.5% versus 57.1%, p = 0.887), infection (5.7% versus 1.8%, p = 0.071), and time to union (median 48 weeks versus 52 weeks, p = 0.643). Data on range of motion were available in 71 patients. There was no significant difference in anteflexion (median 180 degrees anterior versus 180 degrees superior) and abduction (median 180 degrees anterior versus 180 degrees superior) between the two groups. CONCLUSION: This retrospective cohort study did not find sufficient evidence to recommend one implant position over the other for midshaft clavicular fractures with regard to removal due to irritation. Time to union was similar and Infections were equally rare in both groups. Notably, a considerable number of patients in both groups had their implants removed due to irritation. Larger prospective studies are needed to determine how much plate position contributes to the occurrence of irritation and whether other patient or implant-related factors might play a role. Until this is clarified, implant position should be based on surgeons preference and experience.

Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

Proximal humerus fractures are common in an aging population. The standard operative treatment is open reduction internal fixation (ORIF) using an angular stable plate. However, this procedure has complications such as a relatively high rate of secondary dislocation, humeral head necrosis or nonunion caused by delayed bony consolidation. Autologous bone marrow mononuclear cells (BMC) combined with a ß-TCP scaffold could support bone healing and is considered clinically safe. This multicentric, randomized, open phase IIa clinical trial (Clinical Trials. Gov Identifier: NCT02803177, Eudra CT No: 2015-001820-51) evaluated whether autologous BMC with ß-TCP in addition to ORIF reduces the incidence of secondary dislocations in patients with proximal humerus fracture. Ninty-four patients equally divided between verum group (BMC+ß-TCP) and control group (ß-TCP only) were targeted and calculated. At the time of planned interim evaluation, ie, enrolment of 56 patients, no statistical difference in secondary dislocations or complications was demonstrated in either group after an observation period of 12 weeks. Radiographic bone healing and DASH score to determine shoulder function were comparable between both groups. Bone marrow harvest and BMC transplantation did not result in any severe adverse events. Therefore, the study was terminated after the interim analysis, as no other result could be expected. From the study results, it can be concluded that the application of autologous BMC is well tolerated, and bone healing can be achieved. Augmentation of bone defects with ß-TCP could be shown to be feasible and might be considered in other clinical situations.

[Medium-term Results after percutaneous Needle Fasciotomy in Dupuytren's Disease]. / Mittelfristige Ergebnisse nach perkutaner Nadelfasziotomie bei Morbus Dupuytren.

BACKGROUND: Dupuytren's disease often leads to an increasing limitation in finger extension in affected patients. As the incidence rises with age, the number of cases is expected to rise in the future due to the demographic change. Therefore, an easy and patient-oriented treatment is required. In the following study, we investigated the short and medium-term results after percutaneous needle fasciotomy (PNF). PATIENTS AND METHODS: Overall, 65 fingers of 40 patients were treated with PNF. We evaluated the total passive deficit of extension (TPED), the passive deficit of extension of the joints (PED), the Buck-Gramcko score, rate of recurrence, DASH score and patient satisfaction. The average age of the patients was 65,9 years. Most of the patients (82%) were male. RESULTS: Directly after the PNF, extension in the treated fingers improved significantly (TPED before PNF 74,6°±41,1 SD to 32,8°±29,0 SD after the procedure). By the time of the follow-up examination (30,2±13,9 SD months), TPED had increased again (52,7°±40,2 SD). The rate of recurrence was 29,7%, and a higher Tubiana stage before the procedure correlated significantly with a higher recurrence rate. Nevertheless, patients demonstrated a very high level of satisfaction with the procedure and almost all patients would choose to undergo PNF again. CONCLUSION: Although it is associated with a relatively high recurrence rate, PNF represents an effective and patient-oriented treatment of Dupuytren's contracture.

Computer vision-based algorithm to sUppoRt coRrect electrode placemeNT (CURRENT) for home-based electric non-invasive brain stimulation.

OBJECTIVE: Home-based non-invasive brain stimulation (NIBS) has been suggested as an adjunct treatment strategy for neuro-psychiatric disorders. There are currently no available solutions to direct and monitor correct placement of the stimulation electrodes. To address this issue, we propose an easy-to-use digital tool to support patients for self-application. METHODS: We recruited 36 healthy participants and compared their cap placement performance with the one of a NIBS-expert investigator. We tested participants' placement accuracy with instructions before (Pre) and after the investigator's placement (Post), as well as participants using the support tool (CURRENT). User experience (UX) and confidence were further evaluated. RESULTS: Permutation tests demonstrated a smaller deviation within the CURRENT compared with Pre cap placement (p = 0.02). Subjective evaluation of ease of use and usefulness of the tool were vastly positive (8.04 out of 10). CURRENT decreased the variability of performance, ensured placement within the suggested maximum of deviation (10 mm) and supported confidence of correct placement. CONCLUSIONS: This study supports the usability of this novel technology for correct electrode placement during self-application in home-based settings. SIGNIFICANCE: CURRENT provides an exciting opportunity to promote home-based, self-applied NIBS as a safe, high-frequency treatment strategy that can be well integrated in patients' daily lives.

The semiconstrained DRUJ prosthesis: blessing or curse?

PURPOSE: There are numerous operative procedures to treat osteoarthritic changes or a significant instability of the distal radioulnar joint (DRUJ). The key problem of most methods is the destabilization of the forearm leading to secondary painful impingement between the radius and ulna, as well as a significant limitation of forearm rotation. The Aptis-Prosthesis designed by Scheker represents a complete substitute for the DRUJ. It is mostly used after the failure of various treatment options to solve the primary problems (arthritis, instability). We have used this type of prosthesis mostly after multiple operative treatments for more than 25 years. METHODS: In the following retrospective study, we analyzed the data of patients that received an Aptis-prosthesis between 2016 and 2021. We have implanted this prosthesis in 13 cases (11 female, 2 male). Routinely, we document the clinical outcome concerning range of motion (ROM), grip strength, and pain according to numeric rate scaling (NRS) after more than 12 months (month 12-24). In addition, complications, osseous changes, and the rate of loosening of the prosthesis were registered. Furthermore, DASH-Score and patients ' satisfaction were evaluated. Also-as with other implants-follow-up x-rays were performed. RESULTS: Removal or significant revision of any of the prostheses was not needed. The ROM was 68.1° ± 19.7° for pronation and 72.3° ± 20.9° for supination, grip strength amounted to 27.7 kg ± 11.0 kg equaling 83% of the contralateral side. NRS was 0 at rest and 1.2 (0-2) under weight-bearing. A lysis margin of the radial tap was noted in the radiological examination in 2 patients but without any signs of loosening. The DASH-Score added up to 31.8 ± 13.8 (13-55). All patients were satisfied or very satisfied having this implant. CONCLUSION: The semiconstrained Aptis-prosthesis is a safe and efficient treatment option after failed DRUJ surgeries. It is striking that of the 20 implanted prostheses no significant revision or explantations were necessary over a period of 25 years.

A new 3D-printed polylactic acid-bioglass composite for bone tissue engineering induces angiogenesis in vitro and in ovo.

Large bone defects such as those that occur after trauma or resections due to cancer still are a challenge for surgeons. Main challenge in this area is to find a suitable alternative to the gold-standard therapy, which is highly risky, and a promising option is to use biomaterials manufactured by 3D printing. In former studies, we demonstrated that the combination of polylactic acid (PLA) and bioglass (BG) resulted in a stable 3D-printable material, and porous and finely structured scaffolds were printed. These scaffolds exhibited osteogenic and anti-inflammatory properties. This 3D-printed material fulfills most of the requirements described in the diamond concept of bone healing. However, the question remains as to whether it also meets the requirements concerning angiogenesis. Therefore, the aim of this study was to analyze the effects of the 3D-printed PLA-BG composite material on angiogenesis. In vitro analyses with human umbilical vein endothelial cells (HUVECs) showed a positive effect of increasing BG content on viability and gene expression of endothelial markers. This positive effect was confirmed by an enhanced vascular formation analyzed by Matrigel assay and chicken chorioallantoic membrane (CAM) assay. In this work, we demonstrated the angiogenic efficiency of a 3D-printed PLA-BG composite material. Recalling the osteogenic potential of this material demonstrated in former work, we manufactured a mechanically stable, 3D-printable, osteogenic and angiogenic material, which could be used for bone tissue engineering.

Local Gentamicin Fixation with Sprayed Fibrin-An In Vivo Animal Study Reveals New Options to Treat Soft Tissue Infections.

For acute and chronic soft tissue infections, radical surgical debridement is required and is considered the gold standard, along with its immediate systemic antibiotic therapy. Treatment with local antibiotics and/or antibiotic-containing materials is commonly used as an additional tool in clinical practice. Spraying with fibrin and antibiotics is a newer technique that has been studied for some antibiotics. However, for gentamicin, data are not yet available on absorption, optimal application, antibiotic fate at the site and transfer of antibiotic into the blood. In an animal study involving 29 Sprague Dawley rats, 116 back wounds were sprayed with gentamicin using either gentamicin alone or one of two possible spray combinations of gentamicin and fibrin. Simultaneous application of gentamicin and fibrin via a spray system to soft tissue wounds resulted in significant antibiotic concentration over a long period of time. The technique is easy and cost-effective. The systemic crossover was significantly minimized in our study, which may have led to fewer side effects in patients. These results could lead to an improvement in local antibiotic therapy.

A novel measurement strategy and a dedicated sampling cell for the parallel characterization of organic and inorganic constituents in polymer samples by concurrent laser ablation ICP-OES and EI-MS.

Polymeric composite materials are gaining importance due to their universal applicability and easy adaptability for their intended use. For the comprehensive characterization of these materials, the concurrent determination of the organic and the elemental constituents is necessary, which cannot be provided by classical analysis methods. In this work, we present a novel approach for advanced polymer analysis. The proposed approach is based on firing a focused laser beam onto a solid sample placed in an ablation cell. The generated gaseous and particular ablation products are measured online parallelly by EI-MS and ICP-OES. This bimodal approach allows direct characterization of the main organic and inorganic constituents of solid polymer samples. The LA-EI-MS data showed excellent agreement with the literature EI-MS data allowing not only the identification of pure polymers but also of copolymers, as demonstrated with acrylonitrile butadiene styrene (ABS) as the sample. The concurrent collection of ICP-OES elemental data is vital for classification, provenance determination, or authentication studies. The applicability of the proposed procedure has been demonstrated by analysis of various polymer samples from everyday use.

Various effects of 11,12 EET rescue wound healing in a combined model of diabetes and ischemia.

Chronic non healing wounds in diabetic patients still impose a major problem in modern medicine. Especially additional peripheral vascular disease complicates treatment success in these patients. Thus, we analyzed the effects of 11,12 epoxyeicosatrienoic acid (EET) in a combined model of hyperglycemia and ischemia in mice. Hyperglycemia was induced by Streptozotozin 2 weeks prior to wounding. 3 days before wound creation 2 of the 3 suppling vessels of the moue ear were cautherized for ischemia. Either 11,12 EET or solvent for control was applied. Wound closure as well as TNF-α, TGF-ß, SDF-1α, VEGF, CD31, and Ki67 were measured. The wounds closed on day 14.4 ± 0.4 standard deviation (SD). 11,12 EET treatment enhanced healing to 9.8 ± 0.6 SD. TNF-α level was augmented on day 9 compared to control and receded on day 18. TGF-ß seemed to be elevated all days observed after 11,12 EET treatment. SDF-1α was enhanced on day 6 and 9 by 11,12 EET, and VEGF on day 6 and 18 as well as CD13 on day 3, 6, and 18. 11,12 EET did not alter Ki67. 11,12 EET are able to rescue deteriorated wound healing in a combined model of hyperglycamia and ischemia by resolution of inflammation, augmentation of neovascularization and increasing expression of TGF-ß as well as SDF-1α.

MR angiography facilitates the differentiation of aneurysmal from unicameral bone cysts.

OBJECTIVES: The objective of this work was to evaluate the incremental value of MR angiography over plain radiographs and MRI for the differentiation of aneurysmal bone cysts (ABCs) from unicameral bone cysts (UBCs). METHODS: Thirty-six juvenile patients with histologically secured primary ABCs or UBCs were included in this retrospective study. Two radiologists assessed all obtained images in a blinded fashion using a catalog of previously suggested imaging findings. A second readout with supplementary MR angiography images was performed after 8 weeks to prevent observer recall bias. Diagnostic accuracy parameters were calculated for individual imaging findings, and overall diagnostic accuracy and diagnostic confidence were assessed for all readouts. Receiver operating characteristic (ROC) curve comparison was used to determine the incremental value of MR angiography. RESULTS: Of 16 imaging features, only abnormal vascularization in MR angiography provided sufficient diagnostic accuracy for the identification of ABCs. Other imaging features such as fluid-fluid levels and internal septations were insufficient for the differentiation of UBCs from ABCs. Availability of MR angiography images significantly increased diagnostic accuracy (94.4 vs 75.0% and 83.3 vs 69.4%, respectively, p < 0.05) and diagnostic confidence (4.5 vs 3.7, p < 0.05) of reading radiologists. CONCLUSION: The presence of arterial feeders in MR angiography can accurately discriminate primary ABCs from UBCs and increases the diagnostic accuracy and diagnostic confidence of reporting radiologists. ADVANCES IN KNOWLEDGE: Radiographic differentiation of cystic bone lesions such as ABCs and UBCs remains challenging. We demonstrate that MR angiography provides incremental value and suggest inclusion in standard examination protocols.

Sterilization of PLA after Fused Filament Fabrication 3D Printing: Evaluation on Inherent Sterility and the Impossibility of Autoclavation.

Three-dimensional printing, especially fused filament fabrication (FFF), offers great possibilities in (bio-)medical applications, but a major downside is the difficulty in sterilizing the produced parts. This study evaluates the questions of whether autoclaving is a possible solution for FFF-printed parts and if the printer itself could be seen as an inherent sterilization method. In a first step, an investigation was performed on the deformation of cylindrically shaped test parts after running them through the autoclaving process. Furthermore, the inherent sterility possibilities of the printing process itself were evaluated using culture medium sterility tests. It could be shown that, depending on the needed accuracy, parts down to a diameter of 5-10 mm can still be sterilized using autoclaving, while finer parts suffer from major deformations. For these, inherent sterilization of the printer itself is an option. During the printing process, over a certain contact time, heat at a higher level than that used in autoclaving is applied to the printed parts. The contact time, depending on the printing parameters, is calculated using the established formula. The results show that for stronger parts, autoclaving offers a cheap and good option for sterilization after FFF-printing. However, the inherent sterility possibilities of the printer itself can be considered, especially when printing with small layer heights for finer parts.

Epidemiology of carpal fractures: is it only about the scaphoid?

Because of their low incidence, studies about carpal fractures are rare. The aim of the present study was to analyze epidemiology and treatment of fractured carpal bones. We retrospectively analyzed data of 178 patients admitted to our emergency room with carpal fractures over 6 years. More males than woman were injured. In 91%, a CT scan was performed. The most commonly affected bone was the triquetrum followed by the scaphoid. Almost all triquetral fractures were treated conservatively as opposed to perilunate dislocations that were all operated on. Half of all patients with scaphoid fractures were operated. Young men had the highest risk to sustain a carpal fracture. The triquetrum and the scaphoid are most frequently affected. Usually a CT scan is needed. Treatment of scaphoid and perilunate luxation fractures is rather operative whereas the other fractures mostly allow conservative casting. Nevertheless, correct indication for treatment is important to avoid sequelae.

Intensive hands-on microsurgery course provides a solid foundation for performing clinical microvascular surgery.

PURPOSE: Microvascular surgery requires highly specialized and individualized training; most surgical residency training programs are not equipped with microsurgery teaching expertise and/or facilities. The aim of this manuscript was to describe the methodology and clinical effectiveness of an international microsurgery course, currently taught year-round in eight countries. METHODS: In the 5-day microsurgery course trainees perform arterial and venous end-to-end, end-to-side, one-way-up, and continuous suture anastomoses and vein graft techniques in live animals, supported by video demonstrations and hands-on guidance by a full-time instructor. To assess and monitor each trainee's progress, the course's effectiveness is evaluated using "in-course" evaluations, and participant satisfaction and clinical relevance are assessed using a "post-course" survey. RESULTS: Between 2007 and 2017, more than 600 trainees participated in the microsurgery course. "In-course" evaluations of patency rates revealed 80.3% (arterial) and 39% (venous) performed in end-to-end, 82.7% in end-to-side, 72.6% in continuous suture, and 89.5% (arterial) and 62.5% (venous) one-way-up anastomoses, and 58.1% in vein graft technique. "Post-course" survey results indicated that participants considered the most important components of the microcourse to be "practicing on live animals", followed by "the presence of a full-time instructor". In addition, almost all respondents indicated that they were more confident performing clinical microsurgery cases after completing the course. CONCLUSIONS: Microvascular surgery requires highly specialized and individualized training to achieve the competences required to perform and master the delicate fine motor skills necessary to successfully handle and anastomose very small and delicate microvascular structures. The ever-expanding clinical applications of microvascular procedures has led to an increased demand for training opportunities. By teaching time-tested basic motor skills that form the foundation of microsurgical technique this international microsurgery-teaching course is helping to meet this demand.

In vitro Evaluation of a 20% Bioglass-Containing 3D printable PLA Composite for Bone Tissue Engineering.

Three-dimensional (3D) printing is considered a key technology in the production of customized scaffolds for bone tissue engineering. In a previous work, we developed a 3D printable, osteoconductive, hierarchical organized scaffold system. The scaffold material should be osteoinductive. Polylactic acid (PLA) (polymer)/Bioglass (BG) (mineral/ion source) composite materials are promising. Previous studies of PLA/BG composites never exceed BG fractions of 10%, as increase of bioactive BG component negatively affects the printability of the composite material. Here, we test a novel, 3D printable PLA/BG composite with BG fractions up to 20% for its biological activity in vitro. PLA/BG filaments suitable for microstructure 3D printing were spun and the effect of different BG contents (5%, 10%, and 20%) in this material on mesenchymal stem cell (MSC) activity was tested in vitro. Our results showed that all tested composites are biocompatible. MSC cell adherence and metabolic activity increase with increasing BG content. The presence of BG component in scaffold has only slight effect on osteogenic gene expression, but it has significant suppressive effect on the expression of inflammatory genes in MSC. In addition, the material did not provoke any significant inflammatory response in whole-blood stimulation assay. The results show that by increasing the BG content, the bioactivity can be further enhanced.

3D-Printed PLA-Bioglass Scaffolds with Controllable Calcium Release and MSC Adhesion for Bone Tissue Engineering.

Large bone defects are commonly treated by replacement with auto- and allografts, which have substantial drawbacks including limited supply, donor site morbidity, and possible tissue rejection. This study aimed to improve bone defect treatment using a custom-made filament for tissue engineering scaffolds. The filament consists of biodegradable polylactide acid (PLA) and a varying amount (up to 20%) of osteoconductive S53P4 bioglass. By employing an innovative, additive manufacturing technique, scaffolds with optimized physico-mechanical and biological properties were produced. The scaffolds feature adjustable macro- and microporosity (200-2000 µm) with adaptable mechanical properties (83-135 MPa). Additionally, controllable calcium release kinetics (0-0.25 nMol/µL after 24 h), tunable mesenchymal stem cell (MSC) adhesion potential (after 24 h by a factor of 14), and proliferation (after 168 h by a factor of 18) were attained. Microgrooves resulting from the 3D-printing process on the surface act as a nucleus for cell aggregation, thus being a potential cell niche for spheroid formation or possible cell guidance. The scaffold design with its adjustable biomechanics and the bioglass with its antimicrobial properties are of particular importance for the preclinical translation of the results. This study comprehensibly demonstrates the potential of a 3D-printed bioglass composite scaffold for the treatment of critical-sized bone defects.