We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

This paper outlines the recent development of an exchange Travelling Fellowship scheme between the British and American Orthopaedic Research Societies.

Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community.

In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments.

We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers.

The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used.

Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface.

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined.

The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.

The October 2012 Research Roundup³⁶⁰ looks at: whether you can escape your genes; oral prophylaxis for DVT; non-responders and the internet; metal-on-metal, mice and damaged livers; sleeping on the job; cartilage contact stress in the normal human hip; and a perfect reason to subscribe to 360.

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres.

The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.

The October 2012 Foot & Ankle Roundup³⁶⁰ looks at: ankle arthrodesis in young active patients; the Bologna-Oxford total ankle replacements; significant failure and revision rates for total ankle arthroplasty; surgical treatment of Achilles tendon rupture; selective plantar fascia release; whether removal of metalwork can resolve foot pain; allografting of osteochondral lesions; distracting from osteoarthritis; and ultrasound-guided minimally invasive surgery.

The August 2012 Knee Roundup³⁶⁰ looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy.

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T₁, T₂ and T_1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative.

We describe 22 cases of bizarre parosteal osteochondromatous proliferation, or Nora’s lesion. These are surface-based osteocartilaginous lesions typically affecting the hands and feet. All patients were identified from the records of a regional bone tumour unit and were treated between 1985 and 2009. Nine lesions involved the metacarpals, seven the metatarsals, one originated from a sesamoid bone of the foot and five from long bones (radius, ulna, tibia, and femur in two). The mean age of the patients was 31.8 years (6 to 66), with 14 men and eight women. Diagnosis was based on the radiological and histological features. The initial surgical treatment was excision in 21 cases and amputation of a toe in one. The mean follow-up was for 32 months (12 to 162). Recurrence occurred in six patients (27.3%), with a mean time to recurrence of 49 months (10 to 120). Two of the eight patients with complete resection margins developed a recurrence (25.0%), compared with four of 14 with a marginal or incomplete resection (28.6%).

Given the potential surgical morbidity inherent in resection, our data suggest that there may be a role for a relatively tissue-conserving approach to the excision of these lesions.

We retrospectively identified 18 consecutive patients with synovial chrondromatosis of the shoulder who had arthroscopic treatment between 1989 and 2004. Of these, 15 were available for review at a mean follow-up of 5.3 years (2.3 to 16.5). There were seven patients with primary synovial chondromatosis, but for the remainder, the condition was a result of secondary causes. The mean Constant score showed that pain and activities of daily living were the most affected categories, being only 57% and 65% of the values of the normal side. Surgery resulted in a significant improvement in the mean Constant score in these domains from 8.9 (4 to 15) to 11.3 (2 to 15) and from 12.9 (5 to 20) to 18.7 (11 to 20), respectively (unpaired t-test, p = 0.04 and p < 0.0001, respectively). Movement and strength were not significantly affected. Osteoarthritis was present in eight patients at presentation and in 11 at the final review. Recurrence of the disease with new loose bodies occurred in two patients from the primary group at an interval of three and 12 years post-operatively. In nine patients, loose bodies were also present in the bicipital groove; seven of these underwent an open bicipital debridement and tenodesis.

We found that arthroscopic debridement of the glenohumeral joint and open debridement and tenodesis of the long head of biceps, when indicated, are safe and effective in relieving symptoms at medium-term review.

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

Introduction

The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD.

We studied bone-tendon healing using immunohistochemical methods in a rabbit model.

Reconstruction of the anterior cruciate ligament was undertaken using semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were performed at one, two, four and eight weeks after the operation. The expression of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the bone-tendon interface was very similar to that in the endochondral ossification. Some of the type-III collagen in the outer layer of the graft, which was deposited at a very early phase after the operation, was believed to have matured into Sharpey-like fibres. However, remodelling of the tendon grafted into the bone tunnel was significantly delayed when compared with this ossification process. To promote healing, we believe that it is necessary to accelerate remodelling of the tendon, simultaneously with the augmentation of the ossification.

Microfracture is frequently used as the first line of treatment for the repair of traumatic cartilage defects. We present the clinical and histological results 18 months to two-years after treatment in a 26-year-old male with a post-traumatic chondral defect of the medial femoral condyle managed by microfracture covered with chondrotissue, a cell-free cartilage implant made of a resorbable polyglycolic acid felt and hyaluronic acid.

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.