Comparative in vitro treatment of mesenchymal stromal cells with GDF-5 and R57A induces chondrogenic differentiation while limiting chondrogenic hypertrophy.

Purpose: Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotype remains a problem.

PMMA Bone Cement: Antibiotic Elution and Mechanical Properties in the Context of Clinical Use.

This literature review discusses the use of antibiotic loaded polymethylmethacrylate bone cements in arthroplasty. The clinically relevant differences that have to be considered when antibiotic loaded bone cements (ALBC) are used either for long-term implant fixation or as spacers for the treatment of periprosthetic joint infections are outlined. In this context, in vitro findings for antibiotic elution and material properties are summarized and transferred to clinical use.

The Impact of Total Knee Replacement with a Customized Cruciate-Retaining Implant Design on Patient-Reported and Functional Outcomes.

Purpose: To treat patients with tricompartimental knee osteoarthritis (OA), a customized cruciate-retaining total knee arthroplasty (CCR-TKA) system can be used, including both individualized instrumentation and implants. The objective of this monocentric cohort study was to analyze patient-reported and functional outcomes in a series of patients implanted with the second generation of this customized implant.

Methods: At our arthroplasty center, we prospectively recruited a cohort of patients with tricompartmental gonarthrosis to be treated with total knee replacement (TKA) using a customized cruciate-retaining (CCR) implant design.

Patient-specific cruciate-retaining total knee replacement with individualized implants and instruments (iTotal™ CR G2).

Objective: Treatment of tricompartimental osteoarthritis (OA) using customized instruments and implants for cruciate-retaining total knee arthroplasty. Use of patient-specific instruments and implants (ConforMIS iTotal CR G2) together with a 3D-planning protocol (iView®). Retropatellar resurfacing is optional.

Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty.

Background: For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated.

Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer.

Objective: As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors.

Design: Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX) 9, transforming growth factor beta (TGFB) 1 or bone morphogenetic protein (BMP) 2 cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP.

The human arthritic hip joint is a source of mesenchymal stromal cells (MSCs) with extensive multipotent differentiation potential.

Background: While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint.

Methods: MSCs were isolated and multiplied in adherent monolayer cell cultures.

Editorial Commentary: Subacromial Bursa-Friend or Foe Within The Shoulder? An Old Debate With New Insights.

There is an ongoing debate about whether to resect or preserve the subacromial bursa during surgical treatment of rotator cuff tears. Neer was the first to systematically describe bursitis as a component of subacromial impingement syndrome that may extend to rotator cuff disease, often discussed as a point of controversy with Uhthoff who first identified the bursa as a contributor to rotator cuff healing, both experimentally and clinically. Because the subacromial bursa provides the gliding mechanism of the shoulder and regenerates itself after surgical removal, interest evolved on the role of the bursa in the healing of rotator cuff tears for evolution of regenerative therapies as a support of arthroscopic repair techniques.

Tendon-derived stem cells from the long head of the biceps tendon: Inflammation does not affect the regenerative potential.

Objectives: The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration.

High variability of proximal tibial asymmetry and slope: a CT data analysis of 15,807 osteoarthritic knees before TKA.

Purpose: As the correct rotational and sagittal alignment of the tibial tray are of key importance for optimal total knee arthroplasty (TKA) function, the objective of this study was to determine these individual variations in the proximal tibial geometry in terms of posterior tibial slope (PTS) and tibial surface asymmetry by analysing a large dataset of computer tomography (CT) information.

Methods: A retrospective two-part review was performed on 15,807 datasets that were generated during the design phase for a customized TKA implant. First, 15807 CAD (computer-aided-design) models derived from CT data were used to conduct the analysis on the variation of the PTS.

Antibiotic elution and compressive strength of gentamicin/vancomycin loaded bone cements are considerably influenced by immersion fluid volume.

The effect of doubling the immersion fluid (eluate) volume on antibiotic concentrations and on mechanical stability from vancomycin and gentamicin loaded bone cements was investigated in vitro. Antibiotic loaded bone cements containing premixed 1.34% gentamicin antibiotic concentration in the cement powder (wt), premixed 1.

Evaluation of implant fit and frontal plane alignment after bi-compartmental knee arthroplasty using patient-specific instruments and implants.

Introduction: The goals of successful bi-compartmental knee arthroplasty are to achieve correct fit and positioning of the implant, while appropriately correcting the mechanical alignment of the leg after surgery. As these requirements are not always reliably fulfilled using off-the-shelf implant systems, newer approaches for bi-compartmental resurfacing have been explored.

Material And Methods: In this article we report the radiographic results of 30 patients with anteromedial osteoarthritis (OA) who were treated with a novel patient-specific fixed-bearing bi-compartmental knee resurfacing system using custom-made implants and instruments.

TGF-β1-Modified Hyaluronic Acid/Poly(glycidol) Hydrogels for Chondrogenic Differentiation of Human Mesenchymal Stromal Cells.

In cartilage regeneration, the biomimetic functionalization of hydrogels with growth factors is a promising approach to improve the in vivo performance and furthermore the clinical potential of these materials. In order to achieve this without compromising network properties, multifunctional linear poly(glycidol) acrylate (PG-Acr) is synthesized and utilized as crosslinker for hydrogel formation with thiol-functionalized hyaluronic acid via Michael-type addition. As proof-of-principle for a bioactivation, transforming growth factor-beta 1 (TGF-β1) is covalently bound to PG-Acr via Traut's reagent which does not compromise the hydrogel gelation and swelling behavior.

The Mayo conservative hip: complication analysis and management of the first 41 cases performed at a University level 1 department.

Background: To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems.

Methods: In this study, we present a retrospective analysis of the patients' outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients.

Rescued Chondrogenesis of Mesenchymal Stem Cells under Interleukin 1 Challenge by Foamyviral Interleukin 1 Receptor Antagonist Gene Transfer.

Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established model (aggregate culture system) of chondrogenesis in the presence of IL1β.

Loading with vancomycin does not decrease gentamicin elution in gentamicin premixed bone cement.

Antibiotic loaded bone cements are used as drug delivery systems for the treatment of periprosthetic joint infections. They can be loaded with antibiotics during industrial component production (premixing) and during cement preparation (manually blending). Although double premixed antibiotic loaded bone cements are available, manually blending of a gentamicin premixed antibiotic loaded bone cement with vancomycin is still popular.

Case report - calcification of the medial collateral ligament of the knee with simultaneous calcifying tendinitis of the rotator cuff.

Background: Calcification of the medial collateral ligament (MCL) of the knee is a very rare disease. We report on a case of a patient with a calcifying lesion within the MCL and simultaneous calcifying tendinitis of the rotator cuff in both shoulders.

Case Presentation: Calcification of the MCL was diagnosed both via x-ray and magnetic resonance imaging (MRI) and was successfully treated surgically.

[Total knee arthroplasty. Patient-specific instruments and implants].

This article describes the concept and surgical technique of patient-specific total knee arthroplasty. Patient-specific implants and instruments are designed and fabricated based on computed tomography (CT) data of the leg. The disposable patient-specific drill guides and cutting-jigs are manufactured taking into consideration the anatomical and biomechanical axes of the knee joint and mediating the efficient pre-navigation of the osseous saw-cuts, without the need for additional navigation or balancing aids.

Characterization of bursa subacromialis-derived mesenchymal stem cells.

Introduction: The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level.

Methods: BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip.

Ex vivo gene delivery to synovium using foamy viral vectors.

Background: Gene transfer technologies have the potential to fundamentally improve current therapies for arthritic conditions, although this is essentially dependent on safe and efficient vector systems. The foamy virus (FV)-based vectors have many safety features that favour their use in the treatment of arthritis. In the present study, we investigated the use of safe prototype foamy viral vectors (FVV) for indirect gene delivery to articular tissues.

Symptomatic loosening of a total knee arthroplasty caused by a tibial chondrosarcoma - a case report.

Premature implant loosening following total knee arthroplasty (TKA) can have several causes. In this article we report on a rare case of a 74 year old male patient suffering tibial component loosening 14 month after primary TKA. The patient did neither have any malignancies nor joint arthroplasty before.

Synergistic effect of Indian hedgehog and bone morphogenetic protein-2 gene transfer to increase the osteogenic potential of human mesenchymal stem cells.

Introduction: To stimulate healing of large bone defects research has concentrated on the application of mesenchymal stem cells (MSCs).

Methods: In the present study, we induced the overexpression of the growth factors bone morphogenetic protein 2 (BMP-2) and/or Indian hedgehog (IHH) in human MSCs by adenoviral transduction to increase their osteogenic potential. GFP and nontransduced MSCs served as controls.

Foamy virus-adenovirus hybrid vectors for gene therapy of the arthritides.

Background: Genetic treatments of chronic arthritic conditions are essentially dependent on safe and efficient vector systems. To combine features of the efficient transduction of adenovirus vectors with the advantage of stable integration into the host cell genome of apathogenic prototype foamy virus vectors, hybrid vectors (FAD) have been established. In the present study, we have generated and investigated the use of safe FAD vectors for direct gene delivery to joints.

Concise review: the clinical application of mesenchymal stem cells for musculoskeletal regeneration: current status and perspectives.

Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies.

Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells.

Introduction: To date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in human primary MSCs, and whether it was possible by such an approach to modulate the appearance of chondrogenic hypertrophy in pellet cultures in vitro.

Methods: First-generation adenoviral vectors encoding the cDNA of the human IHH gene were created by cre-lox recombination and used alone or in combination with adenoviral vectors, bone morphogenetic protein-2 (Ad.