MRI findings of knee abnormalities in adolescent and adult volleyball players.

Background: To longitudinally and cross-sectionally evaluate knee abnormalities by sex and age in adolescent and adult volleyball athletes over 2 years using magnetic resonance imaging (MRI).

Methods: Thirty-six high-level volleyball athletes (18 adolescents: 56% female, mean age 16.0 ± 0.

Strain shielding inspired re-design of proximal femoral stems for total hip arthroplasty.

A large number of hip prosthesis with different designs have been developed. However, the influence of hip implant design changes on the strains induced in the bone remains unclear. The purpose of this study is to better understand the mechanics of short stem total hip arthroplasty.

The haematoma and its role in bone healing.

Fracture treatment is an old endeavour intended to promote bone healing and to also enable early loading and regain of function in the injured limb. However, in today's clinical routine the healing potential of the initial fracture haematoma is still not fully recognized. The Arbeitsgemeinschaft für Osteosynthesefragen (AO) formed in Switzerland in 1956 formulated four AO principles of fracture treatment which are still valid today.

Mechanosensation across borders: fibroblasts inside a macroporous scaffold sense and respond to the mechanical environment beyond the scaffold walls.

In tissue defects, cells face distinct mechanical boundary conditions, but how this influences early stages of tissue regeneration remains largely unknown. Biomaterials are used to fill defects but also to provide specific mechanical or geometrical signals. However, they might at the same time shield mechanical information from surrounding tissues that is relevant for tissue functionalisation.

[Steel or titanium for osteosynthesis : A mechanobiological perspective].

Background: An implant used for stabilizing a fracture creates a mechanical construct, which directly determines the biology of bone healing. The stabilization of fractures places high mechanical demands on implants and therefore steel and titanium are currently almost exclusively used as the materials of choice.

Objectives: The possible range of attainable mechanobiological stimulation for mechanotherapy as a function of plate stiffness depending on the selection of the plate material and the physical and mechanical properties of the material options are discussed.

Tomography-Based Quantification of Regional Differences in Cortical Bone Surface Remodeling and Mechano-Response.

Bone has an adaptive capacity to maintain structural integrity. However, there seems to be a heterogeneous cortical (re)modeling response to loading at different regions within the same bone, which may lead to inconsistent findings since most studies analyze only one region. It remains unclear if the local mechanical environment is responsible for this heterogeneous response and whether both formation and resorption are affected.

Substrate Stress-Relaxation Regulates Scaffold Remodeling and Bone Formation In Vivo.

The rate of stress relaxation of adhesion substrates potently regulates cell fate and function in vitro, and in this study the authors test whether it can regulate bone formation in vivo by implanting alginate gels with differing rates of stress-relaxation carrying human mesenchymal stem cells into rat calvarial defects. After three months, the rats that received fast-relaxing hydrogels (t ≈ 50 s) show significantly more new bone growth than those that received slow-relaxing, stiffness-matched hydrogels. Strikingly, substantial bone regeneration results from rapidly relaxing hydrogels even in the absence of transplanted cells.

CD31+ Cells From Peripheral Blood Facilitate Bone Regeneration in Biologically Impaired Conditions Through Combined Effects on Immunomodulation and Angiogenesis.

Controlled revascularization and inflammation are key elements regulating endogenous regeneration after (bone) tissue trauma. Peripheral blood-derived cell subsets, such as regulatory T-helper cells and circulating (endothelial) progenitor cells, respectively, can support endogenous tissue healing, whereas effector T cells that are associated with an aged immune system can hinder bone regeneration. CD31 is expressed by diverse leukocytes and is well recognized as a marker of circulating endothelial (precursor) cells; however, CD31 is absent from the surface of differentiated effector T cells.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma.

Treatment with recombinant human bone morphogenetic protein 7 leads to a transient induction of neutralizing autoantibodies in a subset of patients.

Background: Recombinant human bone morphogenetic protein 7 (rhBMP7) is applied for treatment of bone fractures, especially tibial non-unions. Its application may induce autoantibodies (aAB) affecting the targeted and endogenous signaling pathways and in turn negatively impact treatment efficacy.

Methods: Novel and sensitive assays for the quantification of BMP7-aAB and BMP2-aAB were established and used to analyze serum samples from healthy controls (n = 100 men, n = 100 women) and patients with long bone fracture (n = 265) treated or not with rhBMP7.

Longitudinal bone, muscle and adipose tissue changes in physically active subjects - sex differences during adolescence and maturity.

Objectives: To explore changes in bone, muscle and adipose tissue composition in athletes with high physical activity levels at different stages of life.

Methods: Thigh MRIs were acquired at baseline and 2-year follow-up for 20 young (16±1 years) and 20 mature (46±5 years) athletes (10 males, 10 females, respectively). Longitudinal changes in cross-sectional areas (CSAs) of femoral bone, quadriceps muscle, and thigh subcutaneous (SCF) and intermuscular (IMF) adipose tissue were evaluated.

Strategies for Derisking Translational Processes for Biomedical Technologies.

Inefficient translational processes for technology-oriented biomedical research have led to some prominent and frequent failures in the development of many leading drug candidates, several designated investigational drugs, and some medical devices, as well as documented patient harm and postmarket product withdrawals. Derisking this process, particularly in the early stages, should increase translational efficiency and streamline resource utilization, especially in an academic setting. In this opinion article, we identify a 12-step guideline for reducing risks typically associated with translating medical technologies as they move toward prototypes, preclinical proof of concept, and possible clinical testing.

The Restoration of Passive Rotational Tibio-Femoral Laxity after Anterior Cruciate Ligament Reconstruction.

While the anterior cruciate ligament (ACL) is considered one of the most important ligaments for providing knee joint stability, its influence on rotational laxity is not fully understood and its role in resisting rotation at different flexion angles in vivo remains unknown. In this prospective study, we investigated the relationship between in vivo passive axial rotational laxity and knee flexion angle, as well as how they were altered with ACL injury and reconstruction. A rotometer device was developed to assess knee joint rotational laxity under controlled passive testing.

Synthetic niche to modulate regenerative potential of MSCs and enhance skeletal muscle regeneration.

Severe injury to the skeletal muscle often results in the formation of scar tissue, leading to a decline in functional performance. Traditionally, tissue engineering strategies for muscle repair have focused on substrates that promote myogenic differentiation of transplanted cells. In the current study, the reported data indicates that mesenchymal stromal cells (MSCs) transplanted via porous alginate cryogels promote muscle regeneration by secreting bioactive factors that profoundly influence the function of muscle progenitor cells.

Standardized Loads Acting in Hip Implants.

With the increasing success of hip joint replacements, the average age of patients has decreased, patients have become more active and their expectations of the implant durability have risen. Thus, pre-clinical endurance tests on hip implants require defining realistic in vivo loads from younger and more active patients. These loads require simplifications to be applicable for simulator tests and numerical analyses.

Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro.

In hip arthroplasty the implants' articulating surfaces can be made of a cobalt-chromium-molybdenum (CoCrMo) alloy. The use of these metal-on-metal (MoM) pairings can lead to the release of wear products such as metallic particles and dissociated metal species, raising concerns regarding their safety amongst orthopedic surgeons and the public. MoM-wear particles are reported to be heterogeneous in their physicochemical properties, are capable of inducing adverse effects on a cellular level and are thought to be involved in relevant clinical problems like aseptic osteolysis.

A double-layer patch design for local and controlled drug delivery as an intraoperative custom-made implant-coating technology.

Background: The specific biological need of patients frequently becomes obvious just in the intraoperative setting. We hypothesized that a double-layer patch approach that allowed rapid attachment to an implant surface would represent a potential solution for technically challenging intraoperative personalized local drug delivery.

Methods: Dexamethasone-loaded poly[(rac-lactide)-co-glycolide] (PLGA) microparticles were embedded within a polyvinyl alcohol (PVA) patch that was attached to metal implant surfaces by in situ polymerization of alkyl-2-cyanoacrylates (CAs).

Biomechanical competence of six different bone screws for reconstructive surgery in three different transplants: Fibular, iliac crest, scapular and artificial bone.

The goal of this study was to determine a combination of screw and transplantation type that offers optimal primary stability for reconstructive surgery. Fibular, iliac crest, and scapular transplants were tested along with artificial bone substrate. Six different kinds of bone screws (Medartis(©)) were compared, each type utilized with one of six specimens from human transplants (n = 6).

The Periosteal Bone Surface is Less Mechano-Responsive than the Endocortical.

Dynamic processes modify bone micro-structure to adapt to external loading and avoid mechanical failure. Age-related cortical bone loss is thought to occur because of increased endocortical resorption and reduced periosteal formation. Differences in the (re)modeling response to loading on both surfaces, however, are poorly understood.

Generation of an iPS cell line from bone marrow derived mesenchymal stromal cells from an elderly patient.

An induced pluripotent stem cell line was generated from primary human bone marrow derived mesenchymal stromal cells of a 74 year old donor using retroviruses harboring OCT4, SOX2, KLF4 and c-MYC in combination with the following inhibitors TGFβ receptor-SB 431542, MEK-PD325901, and p53-Pifithrin α. Pluripotency was confirmed both in vitro and in vivo.

Establishment of a preclinical ovine screening model for the investigation of bone tissue engineering strategies in cancellous and cortical bone defects.

Background: New tissue engineering strategies for bone regeneration need to be investigated in a relevant preclinical large animal model before making the translation into human patients. Therefore, our interdisciplinary group established a simplified large animal screening model for intramembranous bone defect regeneration in cancellous and cortical bone.

Methods: Related to a well-established model of cancellous drill hole defect regeneration in sheep, both the proximal and distal epimetaphyseal regions of the femur and the humerus were used bilaterally for eight drill hole cancellous defects (Ø 6 mm, 15 mm depth).

Immune modulation as a therapeutic strategy in bone regeneration.

We summarize research approaches and findings on bone healing and regeneration that were presented at a workshop at the 60th annual meeting of the Orthopedic Research Society (ORS) in New Orleans in 2014. The workshop was designed to discuss the role of inflammation in bone regeneration in the context of fundamental biology, and to develop therapeutic strategies that involve immune modulation. Delayed or non-healing of bone is a major clinical problem, with around 10% of fracture patients suffering from unsatisfying healing outcomes.

Biologic-free mechanically induced muscle regeneration.

Severe skeletal muscle injuries are common and can lead to extensive fibrosis, scarring, and loss of function. Clinically, no therapeutic intervention exists that allows for a full functional restoration. As a result, both drug and cellular therapies are being widely investigated for treatment of muscle injury.

BMPs in bone regeneration: Less is more effective, a paradigm-shift.

Worldwide, the clinical application of BMP2 (bone morphogenetic protein 2) has helped an increasing number of patients achieve bone regeneration in a clinical area lacking simple solutions for difficult bone healing situations. In this review, the historical aspects and current critical clinical issues are summarized and positioned against new research findings on efficacy and function of BMP2. Knowledge concerning how the dose of this growth factor as well as its interaction with mechanical loading influences the efficacy of bone regeneration, might open possible future strategies in cases where bony bridging is unachievable so far.