Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System

Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix.Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model.Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA.Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45(+) leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures.Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth

1st EFORT European Consensus: Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices

Innovations in Orthopaedics and Traumatology have contributed to the achievement of a high-quality level of care in musculoskeletal disorders and injuries over the past decades. The applications of new implants as well as diagnostic and therapeutic techniques in addition to implementation of clinical research, have significantly improved patient outcomes, reduced complication rates and length of hospital stay in many areas. However, the regulatory framework is extensive, and there is a lack of understanding and clarity in daily practice what the meaning of clinical & pre‐clinical evidence as required by the MDR is. Thus, understanding and clarity are of utmost importance for introduction of new implants and implant-related instrumentation in combination with surgical technique to ensure a safe use of implants and treatment of patients. Therefore EFORT launched IPSI, The Implant and Patient Safety Initiative, which starting from an inaugural workshop in 2021 issued a set of recommendations, notably through a subsequent Delphi Process involving the National Member Societies of EFORT, European Specialty Societies as well as International Experts. These recommendations provide surgeons, researchers, implant manufacturers as well as patients and health authorities with a consensus of the development, implementation, and dissemination of innovation in the field of arthroplasty. The intended key outcomes of this 1st EFORT European Consensus on “Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices”are consented, practical pathways to maintain innovation and optimisation of orthopaedic products and workflows within the boundaries of MDR 2017/745. Open Access practical guidelines based on adequate, state of the art pre-clinical and clinical evaluation methodologies for the introduction of joint replacements and implant-related instrumentation shall provide hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, Notified Bodies but also for National Institutes and authorities, patient representatives and further stakeholders. We would like to acknowledge and thank the Scientific Committee members, all International Expert Delegates, the Delegates from European National & Specialty Societies and the Editorial Team for their outstanding contributions and support during this EFORT European Consensus

Total Hip Arthroplasty Using Imageless Computer-Assisted Navigation—2-Year Follow-Up of a Prospective Randomized Study

The purpose of this study is to compare computer-assisted to manual implantation-techniques in total hip arthroplasty (THA) and to find out if the computer-assisted surgery is able to improve the clinical and functional results and reduce the dislocation rate in short-terms after THA. We performed a concise minimum 2-year follow-up of the patient cohort of a prospective randomized study published in 2014 and evaluated if the higher implantation accuracy in the navigated group can be seen as an important determinant of success in total hip arthroplasty. Although a significant difference was found in mean postoperative acetabular component anteversion and in the outliers regarding inclination and anteversion (p < 0.05) between the computer-assisted and the manual-placed group, we could not find significant differences regarding clinical outcome or revision rates at 2-years follow-up. The implantation accuracy in the navigated group can be regarded as an important determinant of success in THA, although no significant differences in clinical outcome could be detected at short-term follow-up. Therefore, further long-term follow-up of our patient group is needed

No effect in primary stability after increasing interference fit in cementless TKA tibial components

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Early Results of a New Rotating Hinge Knee Implant

Background. Indication for rotating hinge (RH) total knee arthroplasty (TKA) includes primary and revision cases, with contradictory results. The aim of this study was to report prospective early results of a new modular rotating hinge TKA (EnduRo). For this implant several new design features and a new bearing material (carbon-fiber reinforced poly-ether-ether-ketone) have been developed. Furthermore, we tried to establish a new classification of failure modes for revision TKA. Methods. 152 EnduRo rotating-hinge prostheses were implanted in two centers. In 90 patients a primary implantation has been performed and 62 patients were revision cases. Knee Society Score (KSS), Western Ontario and McMaster Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), and Range of motion (ROM) were assessed before surgery, 3 months postoperatively, 12 months postoperatively, and annually thereafter. We defined 3 types of complications: Type 1, infection; type 2, periprosthetic complications; type 3, implant failures. Results. KSS, WOMAC, OKS, and ROM revealed significant improvements between the preoperative and the follow-up investigations. There were 14 complications (9.2%) leading to revision surgery, predominantly type 2. Conclusion. Our study shows excellent clinical results of the EnduRo TKA. Furthermore, no premature material failure or unusual biological response to the new bearing material could be detected

Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System

Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix.Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model.Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA.Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45+ leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures.Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth

Image_3_Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System.pdf

<p>Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix.</p><p>Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model.</p><p>Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA.</p><p>Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45⁺ leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures.</p><p>Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth.</p

The effect of different interference fits on the primary fixation of a cementless femoral component during experimental testing

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