Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration.

There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration appears to be impaired in case of local accumulation of CD8+ effector T cells (T), impairing endogenous regeneration by increasing a primary "useful" inflammation toward a damaging level. Thus, rescuing regeneration by regulating the heightened pro-inflammatory reaction employing regulatory CD4+ T (T) cells could represent an immunomodulatory option to enhance healing.

Clinical and Research Approaches to Treat Non-union Fracture.

Purpose Of Review: Impaired healing outcomes or even non-unions after bone injury are still a highly relevant problem in the daily clinical life. Especially within an aging population, the occurrence of bone fractures increases and thus novel treatment approaches to overcome compromised bone regeneration are needed.

Recent Findings: The gold standard to treat delayed or non-healing bone injuries is still the use of autologous bone grafts to foster regeneration.

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.

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.

Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.

Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive.

T and B cells participate in bone repair by infiltrating the fracture callus in a two-wave fashion.

Fracture healing is a regenerative process in which bone is restored without scar tissue formation. The healing cascade initiates with a cycle of inflammation, cell migration, proliferation and differentiation. Immune cells invade the fracture site immediately upon bone damage and contribute to the initial phase of the healing process by recruiting accessory cells to the injury site.

Initiation and early control of tissue regeneration - bone healing as a model system for tissue regeneration.

Introduction: Tissue regeneration in itself is a fascinating process that promises repeated renewal of tissue and organs.

Areas Covered: This article aims to illustrate the different strategies available to control tissue regeneration at a very early stage, using bone as an exemplary tissue. The aspects of a controlled inflammatory cascade to achieve a balanced immune response, cell therapeutic approaches for improved tissue formation and angiogenesis, guiding the organization of newly formed extracellular matrix by biomaterials, the relevance of mechanical signals for tissue regeneration processes, and the chances and limitations of growth factor treatments are discussed.

CD133: enhancement of bone healing by local transplantation of peripheral blood cells in a biologically delayed rat osteotomy model.

Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing.

Inflammatory phase of bone healing initiates the regenerative healing cascade.

Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced impaired/delayed bone healing group.

The pin-bone interface in external fixator: a standardized analysis in a sheep osteotomy model.

Objectives: The hypothesis of the study was that the incidence of pin loosening and pin infection would increase, whereas the general stability of the pin-bone interface would decrease with ongoing implantation time. The aim of this study was to analyze the biologic reactions of the bone tissue adjacent to the pin to determine the relationship among the osseous anchorage of pins, the incidence of infections, and the histologic appearance.

Methods: Three groups of sheep received a tibial osteotomy stabilized by external fixators.

Repeatability and reproducibility of OSSCA, a functional approach for assessing the kinematics of the lower limb.

Marker-based gait analysis of the lower limb that uses assumptions of generic anatomical morphology can be susceptible to errors, particularly in subjects with high levels of soft tissue coverage. We hypothesize that a functional approach for assessing skeletal kinematics, based on the application of techniques to reduce soft tissue artefact and functionally identify joint centres and axes, can more reliably (repeatably and reproducibly) assess the skeletal kinematics than a standard generic regression approach. Six healthy adults each performed 100 repetitions of a standardized motion, measured on four different days and by five different observers.

[Clinical research in partnership: musculoskeletal surgery].

As a result of the demographic development of industrial nations the number of musculoskeletal diseases and injuries rises continuously. This challenges health care as well as clinical research and demands additional endeavours. The United Nations have recognised this issue at an early stage.

Cyclic strain disrupts endothelial network formation on Matrigel.

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration.

Insight into the molecular pathophysiology of delayed bone healing in a sheep model.

Delayed and nonunions are still challenging problems. In this study, we examined the endogenous mRNA expression of genes regulating cartilage formation, bone formation, endochondral ossification, and bone remodeling during mechanically induced delayed bone healing in a large animal model. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a rotationally unstable fixator leading to delayed healing.

Stair climbing results in more challenging patellofemoral contact mechanics and kinematics than walking at early knee flexion under physiological-like quadriceps loading.

The mechanical environment during stair climbing has been associated with patellofemoral pain, but the contribution of loading to this condition is not clearly understood. It was hypothesized that the loading conditions during stair climbing induce higher patellofemoral pressures, a more lateral force distribution on the trochlea and a more lateral shift and tilt of the patella compared to walking at early knee flexion. Optical markers for kinematic measurements were attached to eight cadaveric knees, which were loaded with muscle forces at instances of walking and stair climbing cycles at 12 degrees and 30 degrees knee flexion.

Joint line elevation in revision TKA leads to increased patellofemoral contact forces.

One difficulty in revision total knee arthroplasty (TKA) is the management of distal femoral bone defects in which a joint line elevation (JLE) is likely to occur. Although JLE has been associated with inferior clinical results, the effect that an elevated joint line has on knee contact forces has not been investigated. To understand the clinical observations and elaborate the potential risk associated with a JLE, we performed a virtual TKA on the musculoskeletal models of four subjects.

Biaxial cell stimulation: A mechanical validation.

To analyse mechanotransduction resulting from tensile loading under defined conditions, various devices for in vitro cell stimulation have been developed. This work aimed to determine the strain distribution on the membrane of a commercially available device and its consistency with rising cycle numbers, as well as the amount of strain transferred to adherent cells. The strains and their behaviour within the stimulation device were determined using digital image correlation (DIC).

Locally applied osteogenic predifferentiated progenitor cells are more effective than undifferentiated mesenchymal stem cells in the treatment of delayed bone healing.

Mesenchymal stem cells (MSCs) and osteogenic predifferentiated cells (OPCs) have been shown to promote healing of critical-sized bone defects. This study investigated the regenerative capacity of autologous MSCs versus OPCs after local injection into a compromised bone healing situation. We hypothesized that treatment with MSCs and OPCs would enhance the healing and that the MSCs would be more effective due to their lower differentiation and higher proliferative competence.

Influence of scaffold stiffness on subchondral bone and subsequent cartilage regeneration in an ovine model of osteochondral defect healing.

Background: In osteochondral defects, subchondral bone, as a load-bearing structure, is believed to be important for bone and cartilage regeneration.

Hypothesis: A stiff scaffold creates better conditions for bone formation and cartilage regeneration than does a softer one.

Study Design: Controlled laboratory study.

Pressure, oxygen tension and temperature in the periosteal callus during bone healing--an in vivo study in sheep.

Adequate blood supply and sufficient mechanical stability are necessary for timely fracture healing. Damage to vessels impairs blood supply; hindering the transport of oxygen which is an essential metabolite for cells involved in repair. The degree of mechanical stability determines the mechanical conditions in the healing tissues.

A comparison of techniques for fixation of the quadriceps muscle-tendon complex for in vitro biomechanical testing of the knee joint in sheep.

Whilst in vitro testing can contribute to a better understanding of the biomechanical interactions at the knee joint, the application of physiological-like muscle forces in vitro remains challenging. One main difficulty seems to be the adequate fixation of the muscle-tendon complex to the mechanical apparatus that provides the forces in vitro. The goal of this study was to compare the ability of different muscle-tendon fixation mechanisms, including a new technique developed to optimise the interface grip of the soft tissues, to reliably transmit physiological in vivo loads through the muscle-tendon complex to the attached bone.