Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility

Metal meshes are used in revision surgery of the hip to contain impacted bone grafts in cases with cortical or calcar defects in order to provide rotational stability to the stem. However, the viability of bone allografts under these metal meshes has been uncertain. We describe the histological appearances of biopsies obtained from impacted bone allografts to the calcar contained by a metal mesh in two femoral reconstructions which needed further surgery at 24 and 33 months after the revision procedure. A line of osteoid and viable new bone was observed on the surface of necrotic trabeculae. Active bone marrow between these trabeculae showed necrotic areas in some medullary spaces with reparative fibrous tissue and isolated reactive lymphocytes. This is interpreted as reparative changes after revascularisation of the cancellous allografts. These pathological findings are similar to those reported in allografts contained by cortical host bone and support the hypothesis that incorporation of morcellised bone under metal meshes is not affected by these devices

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The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

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To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

Systemic mastocytosis is a rare condition that often involves the bone marrow. We report the case of a patient with systemic mastocytosis who underwent total hip replacement. Technical difficulties encountered during the procedure included a narrow medullary canal and abnormally hard bone, later confirmed by laboratory measurements. Follow-up at five years showed a good clinical and radiological outcome

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Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment

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The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone.

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Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

1. Previous immunological studies have shown that homografts of fresh marrow-free iliac bone are only weakly, if at all, antigenic. 2. In view of this finding an attempt was made to produce a foreign bone graft capable of forming new bone as readily as an iliac autograft by the following method. Living cells of high osteogenic potential and of autologous type were introduced into the graft by combining homologous fresh marrow-free iliac bone with the animal's own red marrow to form a fresh composite homograft-autograft of cancellous bone. 3. Such fresh composite homograft-autografts were inserted into a muscular site in Wistar rats and removed for microscopical examination at intervals of one to seven days and at two, six and twelve weeks after transplantation. 4. It is found that bone and marrow together as a fresh composite homograft-autograft form considerably more new bone than do either of the components of the graft transplanted separately. Homografts of fresh marrow-free iliac bone form, in general, a small amount of early phase and late phase new bone. Autografts of red marrow transplanted alone to a muscular site formed new bone in thirteen to thirty experiments (43 per cent). 5. The stimulus to osteogenesis, and the cellular source of osteoblasts, in marrow autografts is discussed in the light of present knowledge. The concept is suggested that after its transplantation there develops in marrow an inductive system leading to osteoblastic differentiation and bone formation. It is proposed that the necrosis of a portion of a marrow graft liberates osteogenic substances which are taken up by primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of the marrow which are induced, thereby, to differentiate as osteoblasts. 6. The cellular source of osteoblasts in a fresh composite homograft-autograft of cancellous bone is discussed. It is deduced that the new bone is derived mainly from the contained marrow of the graft, by mechanisms similar to those leading to osteoblastic differentiation in transplanted autografts of marrow. 7. The stimulus to the greater formation of new bone by fresh composite autograft-homografts than by autografts of marrow transplanted alone is discussed. Two explanations are suggested: 1) a more extensive necrosis of marrow in a composite homograft-autograft than in marrow transplanted alone; and 2) an inductive effect of bone upon marrow. 8. The new bone formed by autografts of fresh marrow-containing iliac bone, it is concluded, is derived not only from osteoblasts on the surfaces of the grafted bone but also from primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of its marrow. 9. Mechanisms which may play a role in the histogenesis of woven bone are discussed. 10. The significance of the relation of bone and marrow is considered briefly in the light of knowledge concerning the venous patterns of bone and marrow

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The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI.

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Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

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With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

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To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

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We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants.

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Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.