No evidence for intervention-dependent influence of methodological features on treatment effect.

Objectives: The goal of this systematic review was to evaluate if the influence of methodological features on treatment effect differs between types of intervention.

Study Design And Setting: MEDLINE, Embase, Web of Science, Cochrane methodology register, and reference lists were searched for meta-epidemiologic studies on the influence of methodological features on treatment effect. Studies analyzing influence of methodological features related to internal validity were included.

Spine surgery research: on and beyond current strategies.

Background Context: Systematic reviews of the literature are powerful tools in evidence-based medicine. However, the design and report of systematic reviews in spinal surgery contain many aspects amenable to improvement.

Purpose: To discuss the issues especially relevant for systematic reviews in spinal surgery.

Total disc replacement for chronic discogenic low back pain: a Cochrane review.

Study Design: Systematic literature review.

Objective: To assess the effect of total disc replacement for chronic low back pain due to lumbar degenerative disc disease compared with fusion or other treatment options.

Summary Of Background Data: There is an increasing use in disc replacement devices for degenerative disc disease, but their effectiveness compared with other interventions such as fusion of the motion segment or conservative treatment remains unclear.

Effect of methodological quality measures in spinal surgery research: a metaepidemiological study.

Background Context: Methodological quality measures of trials in meta-analyses have been shown to influence the pooled effect sizes in several medical fields. However, for spinal surgery, influence of quality measures has not been assessed.

Purpose: The purpose of this study was to analyze the influence of quality measures in studies on effectiveness in spinal surgery.

Scaffolds with a standardized macro-architecture fabricated from several calcium phosphate ceramics using an indirect rapid prototyping technique.

Calcium phosphate ceramics, commonly applied as bone graft substitutes, are a natural choice of scaffolding material for bone tissue engineering. Evidence shows that the chemical composition, macroporosity and microporosity of these ceramics influences their behavior as bone graft substitutes and bone tissue engineering scaffolds but little has been done to optimize these parameters. One method of optimization is to place focus on a particular parameter by normalizing the influence, as much as possible, of confounding parameters.

Growth factor interactions in bone regeneration.

Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors.

Micro-CT quantification of subchondral endplate changes in intervertebral disc degeneration.

Background: The intervertebral disc (IVD) is dependent on nutrient provision through a cartilage layer with underlying subchondral bone, analogous to joint cartilage. In the joint, subchondral bone remodeling has been associated with osteoarthritis (OA) progression due to compromised nutrient and gas diffusion and reduced structural support of the overlaying cartilage. However, subchondral bone changes in IVD degeneration have never been quantified before.

Hypertrophic differentiation and calcification during intervertebral disc degeneration.

Background: In degenerative intervertebral discs (IVDs) collagen type X expression and calcifications have been demonstrated, resembling advanced osteoarthritis (OA), which is associated with hypertrophic differentiation, characterized by the production of collagen type X, Runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), alkaline phosphatase (ALP) and calcifications.

Objective: The aim of this study was to determine if hypertrophic differentiation occurs during IVD degeneration.

Methods: IVDs from all Thompson degeneration grades were prepared for histology, extraction of nucleus pulposus (NP) and annulus fibrosis (AF) tissue (N=50) and micro-CT (N=27).

The presence of extracellular matrix degrading metalloproteinases during fetal development of the intervertebral disc.

Matrix metalloproteinases (MMPs) regulate connective tissue architecture and cell migration through extracellular matrix (ECM) degradation and are associated with both physiological and pathological processes. Although they are known to play a role in skeletal development, little is known about the role of MMPs in intervertebral disc (IVD) development. Sixteen fetal human lumbar spine segments, obtained at autopsy, were compared with five normal, non-fetal L4-L5 IVDs.

Replacement of the medial tibial plateau by a metallic implant in a goat model.

The purposes of the present study were to explore the surgical possibilities for replacement of the medial tibial plateau by a metallic implant in a large animal model and to examine the implications for the opposing cartilage. In six goats, the medial tibial plateau of the right knee was replaced by a cobalt-chromium implant, using polymethylmethacrylate bone cement for fixation. The unoperated left knee served as a control.

Cartilage degeneration in the goat knee caused by treating localized cartilage defects with metal implants.

Objective: The purpose of the current study was to investigate the feasibility of applying defect-size femoral implants for the treatment of localized cartilage defects in a 1-year follow-up model.

Methods: In 13 goats, a medial femoral condyle defect was created in both knees. Defects were randomly treated by immediate placement of an oxidized zirconium (OxZr) (n=9) or cobalt-chromium (CoCr) implant (n=9) or left untreated (n=8).

Goat bone tissue engineering: comparing an intramuscular with a posterolateral lumbar spine location.

The aim of this study was to investigate the effect of implant location on bone formation in goats using autologous bone marrow-derived stromal cells in porous calcium phosphate scaffolds. Intramuscular locations were compared to posterolateral spine fusion locations in eight goats. As scaffolds, we used biphasic calcium phosphate porous blocks of 5 x 5 x 5 mm.

Orthotopic location has limited benefit from allogeneic or autologous multipotent stromal cells seeded on ceramic scaffolds.

Improvement of tissue-engineered grafts is still a challenge in the field of regenerative medicine. Using multipotent stromal cells (MSCs), which have immunosuppressive qualities in an allogeneic situation, off-the-shelf implants can be created. This study compared allogeneic and autologous MSCs at an orthotopic (L1 transverse process model) and ectopic (intramuscular) implantation location in 2-year-old goats.

Articular cartilage degeneration following the treatment of focal cartilage defects with ceramic metal implants and compared with microfracture.

Background: Localized cartilage defects are frequently associated with joint pain, reduced function, and a predisposition to the development of osteoarthritis. The purposes of the current study were to investigate the feasibility of the application of defect-sized femoral implants for the treatment of localized cartilage defects and to compare this treatment, in terms of joint degeneration, with the use of microfracture in a goat model of established cartilage defects.

Methods: In nine Dutch milk goats, a defect in the medial femoral condyle was created in both knees.

In vivo matrix production by bone marrow stromal cells seeded on PLGA scaffolds for ligament tissue engineering.

Ligament tissue engineering based on cell-seeded biomechanically functional constructs is a commonly studied strategy toward native anterior cruciate ligament replacement. Little is known about the survival and differentiation of the seeded cells after the transplantation. We applied retroviral genetic marking to trace implanted cells and studied their differentiation by species-specific immunolabeling of the extracellular matrix produced.

Relating cell proliferation to in vivo bone formation in porous Ca/P scaffolds.

Most current methods for cell monitoring on 3D porous scaffolds involve end-stage investigation of scaffolds. Repeated measurements on scaffolds, without disturbing cell vitality and proliferation, are needed to relate in vitro to in vivo data. Alamar Blue was used for this purpose.

No efficacy of silver bone cement in the prevention of methicillin-sensitive Staphylococcal infections in a rabbit contaminated implant bed model.

Data from literature showed that a new type of metallic silver PMMA cement had good results in infection prophylaxis. This study investigated the in vivo efficacy of silver cement in the prevention of methicillin-sensitive Staphylococcal infections, compared to plain and tobramycin-containing cement. In 48 rabbits, 0.

Prophylaxis of infection and effects on osseointegration using a tobramycin-periapatite coating on titanium implants--an experimental study in the rabbit.

No options are available for local antibiotic delivery from uncemented implants. By loading a porous titanium implant with a biomimetic HA-coating (PeriApatite, PA) with antibiotics, we could obtain adequate local antibiotic concentrations and reduce infection susceptibility. This study investigated the efficacy of a tobramycin-loaded PA-coated titanium foam implant in preventing infection, as well as the effects on osseointegration.

The effect of timing of mechanical stimulation on proliferation and differentiation of goat bone marrow stem cells cultured on braided PLGA scaffolds.

Bone marrow stromal cells (BMSCs) have been shown to proliferate and produce matrix when seeded onto braided poly(L-lactide/glycolide) acid (PLGA) scaffolds. Mechanical stimulation may be applied to stimulate tissue formation during ligament tissue engineering. This study describes for the first time the effect of constant load on BMSCs seeded onto a braided PLGA scaffold.

Cartilage damage caused by metal implants applied for the treatment of established localized cartilage defects in a rabbit model.

The purpose of the current study was to investigate the feasibility of the application of defect-size femoral implants in a rabbit model of established cartilage defects and compare this treatment to microfracturing. In 31 New Zealand White rabbits, a medial femoral condyle defect was created in each knee. After 4 weeks, 3 animals were killed for defect baseline values.

Comparing various off-the-shelf methods for bone tissue engineering in a large-animal ectopic implantation model: bone marrow, allogeneic bone marrow stromal cells, and platelet gel.

Construction of bone grafts for regenerative medicine would highly benefit from off-the-shelf components, such as allogeneic bone marrow stromal cells (BMSCs) and blood-derived growth factors from platelet concentrate. Although allogeneic BMSCs are considered immunosuppressive, their use in transplantation studies is still cautioned. In this study, we used off-the-shelf goat allogeneic BMSCs, per-operatively aspirated bone marrow (BM) and platelet gel (PLG).

Analysis of the dynamics of bone formation, effect of cell seeding density, and potential of allogeneic cells in cell-based bone tissue engineering in goats.

After decades of research, relatively little is known about the role of bone marrow stromal cells (BMSCs) for bone tissue engineering. Although homogeneous cell seeding is regarded optimal, cell survival in large constructs is unlikely, except for the very periphery. Also no minimal and optimal BMSC densities have been identified.

In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers.

The efficacy and benefits of high-dose antibiotic cement spacers compared with beads in the treatment of an infected prosthesis have been shown. However, in clinical practice, commercial, low-dose antibiotic bone cement is often used. This study investigated the in vitro antibiotic release of hip spacers made from Refobacin-Palacos-R or Antibiotic-Simplex-P cement compared with Septopal beads.