Although the response of macrophages to polyethylene debris has been widely studied, it has never been compared with the cellular response to ceramic debris. Our aim was to investigate the cytotoxicity of ceramic particles (Al. 2. O. 3. and ZrO. 2. ) and to analyse their ability to stimulate the release of inflammatory mediators compared with that of high-density polyethylene particles (HDP). We analysed the effects of particle size, concentration and composition using an in vitro model. The J774 mouse macrophage cell line was exposed to commercial particles in the phagocytosable range (up to 4.5 μm). Al. 2. O. 3. was compared with ZrO. 2. at 0.6 μm and with HDP at 4.5 μm. Cytotoxicity tests were performed using flow cytometry and macrophage cytokine release was measured by ELISA. Cell mortality increased with the size and concentration of Al. 2. O. 3. particles. When comparing Al. 2. O. 3. and ZrO. 2. at 0.6 μm, we did not detect any significant difference at the concentrations analysed (up to 2500 particles per macrophage), and mortality remained very low (less than 10%). Release of TNF-α also increased with the size and concentration of Al. 2. O. 3. particles, reaching 195% of control (165 pg/ml v 84 pg/ml) at 2.4 μm and 350 particles per cell (p < 0.05). Release of TNF-α was higher with HDP than with Al. 2. O. 3. particles at 4.5 μm. However, we did not detect any significant difference in the release of TNF-α between Al. 2. O. 3. and ZrO. 2. at 0.6 μm (p > 0.05). We saw no evidence of release of interleukin-1α or interleukin-1ß after exposure to ceramic or HDP particles

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called ‘stem cell’ preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers.

Cite this article: Bone Joint J 2020;102-B(2):148–154

Objectives

Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice.

Aims

Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma.

1. The changes resulting from superficial scarification of articular cartilage have been observed in the knee joint of adult rabbits. A reduction in the amount of stainable matrix ground substance occurred at the sites of damage. Particular attention was therefore paid to sulphated mucopolysaccharide synthesis by cartilage cells in or near the traumatised areas. 2. The femoral groove cartilage one week after scarification showed evidence of increased mucopolysaccharide synthesis, especially by the more superficial chondrocytes near the cuts, but three or four weeks later the enhanced chondrocyte activity tended to diminish, and after six weeks the superficial cells near the cuts were found to be inactive. From six to thirty-four weeks the loss of stainable ground substance extended more deeply, but cell degeneration in these deeper areas of matrix depletion was preceded by a period in which many of the deeper chondrocytes still showed evidence of active mucopolysaccharide synthesis. Cellular activity in tags of depleted cartilage was usually lost before the tags finally disintegrated. Chondrocyte clusters were often seen in the scarified areas, especially in the deeper zones. They seemed to be a reactive rather than degenerative phenomenon. 3. In the scarified cartilages of the patella examined after one week a reactive response by superficial chondrocytes was less evident than in the femoral cartilage from the same joint, and after six weeks areas of deeply extending matrix loss were exceptional. 4. The structural and functional changes in the rabbits' femoral articular cartilage after its scarification resembled those which have been observed in the developing cartilage lesion of human osteoarthritis–namely, loss of interstitial matrix and superficial fibrillation, a stimulated synthesis of chondroitin sulphate by the chondrocytes, and the appearance of cell clusters in the deeper zones. Within the period of the experiment, up to thirty-four weeks, the joint lesions remained strictly localised to the traumatised areas ofcartilage, and exposure of bone and joint remodelling, which are features of advanced osteoarthritis in man, were not seen

1. In the first 1600 of the series of peripheral nerve injuries treated during the years 1940-45 at the Peripheral Nerve Injuries Unit, Oxford, 52 per cent. were due to penetrating wounds, and 6 per cent. of these involved the brachial plexus. 2. A specific method of grouping and grading recovery is described: Group I—lesions of the roots and trunk of C.5, 6; Group II—lesions of the posterior cord; Group III—lesions of C.8, T.1, and the medial cord. 3. The recovery of cases in Group I was good, in Group II fair, and in Group III poor. 4. The brachial plexus was explored on twenty-two occasions. Only in four instances was there interruption of continuity—which is in striking contrast with the frequency in more distal degenerative nerve lesions in open wounds. 5. There is no evidence to suggest that neurolysis influenced motor or sensory recovery, but on one occasion it relieved persistent pain in the limb. In general the correlation between operative findings and prognosis was not precise. 6. With one exception, no recovery of consequence took place in the small muscles of the hand after a lesion in continuity, although galvanic stimulation to all paralysed muscles had been given regularly. 7. There is evidence to suggest that innervation of the biceps may not always be limited to C.5 and 6 and that in a proportion of cases C.7 may make a substantial contribution. 8. In five cases (12 per cent.) Horner's syndrome was present; the causation is discussed. 9. In every case of damage to a main vessel there was a marked tendency to joint stiffness, particularly in the hand, but on one occasion only was there evidence of ischaemic changes in the muscles and nerves. 10. The good spontaneous recovery which occurred in Groups I and II; the poor recovery in Group III even in cases where there was an apparently favourable lesion in continuity; the rarity with which division of nerves was found at operation; and the discouraging results of repair in three cases; make it necessary to conclude that routine exploration of open wounds of the brachial plexus is neither profitable nor justifiable

Abstract

Nerve transfer has become a common and often effective reconstructive strategy for proximal and complex peripheral nerve injuries of the upper limb. This case-based discussion explores the principles and potential benefits of nerve transfer surgery and offers in-depth discussion of several established and valuable techniques including: motor transfer for elbow flexion after musculocutaneous nerve injury, deltoid reanimation for axillary nerve palsy, intrinsic re-innervation following proximal ulnar nerve repair, and critical sensory recovery despite non-reconstructable median nerve lesions.

Aims

Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation.

Aims

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

Objectives

Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that ^99mTc-methylene diphosphonate (^99mTc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA).

1. The clinical and radiological results of seventy-one osteotomies for primary osteoarthritis of the hip performed with internal fixation have been examined two to eight years after operation. Advanced cases where osteotomy would have been purely a salvage procedure were excluded. 2. The hips were divided into two groups: one in a relatively early and the other in a later intermediate stage of the disease. The two criteria for inclusion in the "early" group were a) fiexion movement of 90 degrees or more, either with the patient conscious or completely relaxed under anaesthesia, and b) no collapse of bone seen in the radiograph. 3. The clinical results show that early osteotomy seldom fails to give relief of pain, which is closely correlated with improved function and a favourable assessment of the operation by the patient. A good range of flexion, not less than 70 degrees and frequently 90 degrees, is retained when the criteria mentioned above obtain. 4. The radiological assessment was based upon examination of the joint space, the cystic appearances and the degree of collapse of bone, if any, as seen in serial films. There was convincing evidence of regression indicating arrest of the arthritic process in 70 per cent of the "early" cases. 5. Regression after osteotomy appears to be a well-defined process which is more commonly observed and more complete when the osteotomy is performed sooner rather than at a later stage of the disease. With few exceptions a good radiological result is associated with a good clinical result. 6. Some of the possible causes of failure are discussed. Osteotomy is more likely to fail if delayed till stiffness is severe and collapse of bone has begun. Large cysts, rapid advance of the disease, and a valgus osteotomy in the presence of lateral subluxation may also prejudice the results. 7. This review offers good support for Nissen's suggestion that in primary osteoarthritis of the hip osteotomy should be performed early, while the joint is still mobile and capable of repair, in order to retain good function. 8. Relief from pain is not the only consideration in deciding when to operate; the prospects of arresting the disease and of stimulating a healing reaction in the disordered cancellous bone and articular cartilage by early osteotomy should always be kept in mind. 9. In many respects the findings of this review are complementary to those of Postel and Vaillant (1962) who reported excellent results from varus osteotomy of Pauwels' type in a series of cases of subluxation of the hip with pain but without frank secondary osteoarthritic change

Aims

Postoperative rehabilitation regimens following ankle arthrodesis vary considerably. A systematic review was conducted to determine the evidence for weightbearing recommendations following ankle arthrodesis, and to compare outcomes between different regimens.

Objectives

Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery.

Objectives

MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.

1. This is a simple clinical study of the end-results of arthrodesis of the hip joint in patients followed up and re-examined five to twenty-five years after operation. 2. The study was stimulated by our astonishment at recent reports which suggested that arthrodesis of the hip caused serious operative mortality, a high rate of wound infection, and failure of sound fusion in one of every two cases; and that even when sound fusion was gained there was always pain in the back and usually stiffness of the knee. To say that we were astonished puts it mildly. 3. This review includes 120 patients aged from ten to seventy years, treated for osteoarthritis of the hip joint by intra-articular arthrodesis with the internal fixation of a nail, usually with an iliac graft, and with immobilisation in plaster for not less than four months. 4. Of these 120 patients there was sound fusion of the joint, proved radiographically, in 94 per cent; a mortality of nil; and recovery of free movement of the knee joint to the right angle or far beyond in 91·5 per cent. Almost half of the patients regained normal movement, the heel touching the buttock. Only in eight patients was there less than right-angled flexion. 5. There was no pain in the back—none whatever—in 64 per cent of the patients. In 36 per cent there was some pain or discomfort. One alone said that the low back pain was worse than before the operation. Many others said that pain in the back had been relieved by the operation. 6. It is emphasised that these results were gained only from sound fixation of the joint in the mid-position with neutral rotation, no more abduction than is needed to correct true shortening, and no more flexion of the joint than that with which the patient lies on the table. The limb was immobilised in plaster for at least four months after operation. The stiff knee was mobilised by the patient's own exercise without passive stretching, force or manipulation. 7. Two other groups of patients are considered. There are fourteen treated by fixation of the joint with nail alone, an operation that was never intended to arthrodese the joint and which has long since been abandoned. The other small group is that of patients with old unreduced traumatic dislocation of the hip, a procedure in which the risks of operation are so great and the number of successful results so small as to dissuade us from attempting operative reduction. 8. After successful arthrodesis of the hip joint patients can return to every household activity and every recreation including ski-ing, mountaineering, rock climbing, or whatever else they want

Objectives

Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age.

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.