Objectives

The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels.

The experiments were performed to answer three main questions. These and our answers may be summarised as follows. What is the precise mechanism of healing of a raw bony surface in a joint? What cells are involved? Where do they originate?—In all the implant experiments and in the control series the fundamental mechanism of healing was similar. 1. A massive proliferation of fibroblasts occurred from the cut periosteum, from the cut joint capsule, and to a lesser extent from the medullary canal. 2. Fibroblasts grew centripetally in the first few weeks after operation, attempting to form a "fibroblast cap" to the cut bone end. 3. Fibroblasts of this cap near the cut bone spicules metamorphosed to become prechondroblasts, chondroblasts laying down cartilage matrix, and hypertrophied (alkaline phosphatase-secreting) chondrocytes lying in a calcified matrix. 4. This calcified cartilage matrix was invaded by dilated capillaries probably bearing osteoblasts which laid down perivascular (endochondral) bone. 5. Some of the cells of projecting bone spicules died and their matrix was eroded in the presence of many osteoclasts. 6. In the control experiments of simple excision of the radial head new bone was produced at the periphery only by processes (3) and (4). This sealed off the underlying peripheral cortical bone from the superficially placed peripheral articular surface of fibrocartilage. At about a year from operation the central portion of the articular surface was still formed of bare bone, or of bone spicules covered by a thin layer of irregularly arranged collagen fibres. The opposite capitular articular cartilage was badly eroded. Does the introduction of a dead cartilage implant over the raw bone end affect in any way the final constitution of the new articular surface?—In the implant experiments the new bone produced by processes (3) and (4) formed, after about a year, a complete cortical plate which entirely sealed off the cut end of the radius and left a superficially placed articular covering of smooth fibrocartilage, closely resembling a normal joint surface. The opposite capitular articular surface was normal. What is the final fate of such an implant?—Whale cartilage implants underwent replacement by fibroblasts and collagen fibres, and took about nine months to disappear. The cartilage of fixed autotransplants and homotransplants underwent similar gradual replacement, and took about the same time in each case. The dead bone, implanted in association with the cartilage in both cases, acted as a nidus for hyaline cartilage production by chondrocytes derived from fibroblasts. This cartilage underwent endochondral ossification. This observation suggests that induction by non-cellular osseous material is a factor in chondrification and ossification. All the implants functioned as temporary articular menisci or in some cases as temporary radial articular surfaces. They were always replaced by a permanent fibrocartilaginous meniscus, or a fibrocartilaginous articular surface. An implant did, in fact, always act as a temporary protecting cap and mould for the subjacent growth offibroblasts which was necessary for the production of a satisfactory new joint surface

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.

Aims

To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice.

The development and pre-clinical evaluation of nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated with titanium dioxide (TiO₂) nanotube arrays is reviewed. In vitro and in vivo evaluations show that TiO₂ nanotubes on Ti surfaces positively affect the osseointegration, cell differentiation, mineralisation, and anti-microbial properties. This surface treatment can be superimposed onto existing macro and micro porous Ti implants creating a surface texture that also interacts with cells at the nano level. Histology and mechanical pull-out testing of specimens in rabbits indicate that TiO₂ nanotubes improves bone bonding nine-fold (p = 0.008). The rate of mineralisation associated with TiO₂ nanotube surfaces is about three times that of non-treated Ti surfaces. In addition to improved osseointegration properties, TiO₂ nanotubes reduce the initial adhesion and colonisation of Staphylococcus epidermidis. Collectively, the properties of Ti implant surfaces enhanced with TiO₂ nanotubes show great promise.

Cite this article: Bone Joint J 2018;100-B(1 Supple A):9–16.

Objectives

Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol.

Objectives

Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline.

Objectives

This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis.

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.

Aims

In the 1990s, a bioactive bone cement (BABC) containing apatite-wollastonite glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl methacrylate resin was developed at our hospital. In 1996, we used BABC to fix the acetabular component in primary total hip arthroplasty (THA) in 20 patients as part of a clinical trial. The purpose of this study was to investigate the long-term results of primary THA using BABC.

Objectives

Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures.

Objectives

The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.

Objectives

The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).

Aims

Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship.

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration.

Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Objectives

Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the ‘race for the surface’ theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied.

Aims

Tantalum (Ta) trabecular metal components are increasingly used to reconstruct major bone defects in revision arthroplasty surgery. It is known that some metals such as silver have antibacterial properties. Recent reports have raised the question regarding whether Ta components are protective against infection in revision surgery. This laboratory study aimed to establish whether Ta has intrinsic antibacterial properties against planktonic bacteria, or the ability to inhibit biofilm formation.

Objectives

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis.

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation.

Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.