The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

A retrospective study of 23 acetabular fractures in patients up to 17 years of age is presented, with an average follow-up of eight years. Good or excellent functional results were achieved in 21 patients; radiographic results were good or excellent in 16. Conservative treatment gave consistently good results in fractures with minimal initial displacement, stable posterior fracture-dislocations and Salter-Harris type 1 and 2 triradiate cartilage fractures. Less favourable results were seen in type 5 triradiate cartilage fractures and in comminuted fractures, but operation was no better. Unstable posterior fracture-dislocations and irreducible central fracture-dislocations need operative treatment but the results may still be unsatisfactory

We assessed patellofemoral joint function by combining the measurement of maximal isometric extensor torque at the knee with clinical and radiological measurements in order to calculate the patellofemoral contact force. Eighteen volunteers established the normal ranges of results and the reliability of the system. Of the 39 patients with a variety of knee problems, 29 had anterior knee pain, and all had a subsequent arthroscopy. Patients with anterior knee pain and lesions in the patellar cartilage had significantly reduced isometric contact forces, but those with normal patellofemoral cartilage had normal contact forces. Our method may be useful in providing an objective assessment of anterior knee pain and a quantitative means of monitoring its treatment

We describe a lumbar facet syndrome in which disabling symptoms are associated with normal or near-normal plain radiographs. Local spinal fusion relieved symptoms in 12 patients; the excised facet joint surfaces showed some of the histological changes seen in chondromalacia patellae and in osteoarthritis of other large joints. The most frequent change was focal full-thickness cartilage necrosis or loss of cartilage with exposure of subchondral bone, but osteophyte formation was remarkably absent in all specimens. We suggest that there are both clinical and histological similarities between the facet arthrosis syndrome and chondromalacia patellae. Facet arthrosis may be a relatively important cause of intractable back pain in young and middle-aged adults

We prospectively examined the physical and imaging findings, including MRI, of 23 patients with spontaneous osteonecrosis of the knee after obtaining informed consent to acquire tissue specimens at surgery. There were four men and 19 women, with a mean age of 67.5 years (58 to 77). Plain radiographs were designated as stages 1, 2, 3 or 4 according to the classification of Koshino. Five knees were classified as stage 1, five as stage 2, seven as stage 3 and six as stage 4. The histological specimens were stained with haematoxylin and eosin and tetrachrome. In the early stages of the condition, a subchondral fracture was noted in the absence of any features of osteonecrosis, whereas in advanced stages, osteonecrotic lesions were confined to the area distal to the site of the fracture which showed impaired healing. In such cases, formation of cartilage and fibrous tissue, occurred indicating delayed or nonunion. These findings strongly suggest that the histopathology at each stage of spontaneous osteonecrosis is characterised by different types of repair reaction for subchondral fractures

Aims

The diagnosis of developmental dysplasia of the hip (DDH) is challenging owing to extensive variation in paediatric pelvic anatomy. Artificial intelligence (AI) may represent an effective diagnostic tool for DDH. Here, we aimed to develop an anteroposterior pelvic radiograph deep learning system for diagnosing DDH in children and analyze the feasibility of its application.

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson’s ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique

We have investigated the changes in the interposed capsule after a Chiari pelvic osteotomy, in an experimental study on dysplastic hips in 20 adolescent rabbits. Radiographic, macroscopic and microscopic observations were made up to 12 months after operation. The new acetabular roof had incorporated the interposed capsule and remodelled completely by six months. By 12 months there was a new, stable hip with continuity between the capsule and the original acetabular cartilage. Histologically, the capsule underwent metaplastic change to fibrocartilaginous tissue after six months, with some hyaline-like cartilage near the joint surface. These changes in the interposed capsule play an important role in the formation of a new joint after a Chiari pelvic osteotomy

Aims

This study aimed to identify the tibial component and femoral component coronal angles (TCCAs and FCCAs), which concomitantly are associated with the best outcomes and survivorship in a cohort of fixed-bearing, cemented, medial unicompartmental knee arthroplasties (UKAs). We also investigated the potential two-way interactions between the TCCA and FCCA.

Hemiarthroplasty of the hip and some other joints has been used for many years with satisfactory results, but the fate of articular cartilage when weight-bearing against metal has not been reported. Replacement of the head of the femur was carried out in one hip of each of 26 dogs, and the changes in acetabular cartilage studied at intervals of up to 24 weeks. There was early loss of proteoglycan, followed by surface damage to the cartilage, progressive degenerative changes, and growth of pannus from the articular margins. At 24 weeks after operation there was little remaining articular cartilage, while intense subchondral activity suggested that the bony skeleton was being remodelled to conform to the shape of the prosthesis. This study is not intended to suggest that hemiarthroplasty does not help patients

1. Six cases of necrosis of articular cartilage complicating slipping of the upper femoral epiphysis are reviewed: histological examination in one case showed death of the superficial two-thirds of the articular cartilage, with survival of a layer of basal chondrocytes. In all six cases, after severe initial reduction of joint space as seen radiographically, there was gradual return of joint space, suggesting some regeneration of articular cartilage. The prognosis after cartilage necrosis is therefore not always so bad as has been supposed. 2. Various hypotheses concerning the cause of cartilage necrosis complicating slipped epiphysis are reviewed. The precise cause remains unknown, but there is substantial evidence against its being a consequence of ischaemia of the femoral head

We describe a method which may be useful for the selection of samples for the study of early fibrillation in human articular cartilage. Blocks of cartilage and bone were cut post-mortem from the medial tibial condyles of 29 male and 31 female subjects and the grade of fibrillation was assessed from sections. Contiguous, unfixed blocks of cartilage from the same surface were immersed in a solution of the dye Light Green SF. Sections of these blocks were cut and the rate of penetration of the dye measured at 30 equidistant points across the condylar surface. The relationship between the grade of fibrillation and the rate of dye diffusion was then determined. We demonstrated a significant correlation between the two variables. This technique may make it possible to detect a pre-fibrillary state in apparently normal specimens

Medial tibial plateaux excised during 46 unicompartmental arthroplasties for osteoarthritis were collected and photographed. The anterior cruciate ligament was intact in all joints. In every case the cartilage and bone erosion was centred anteriorly on the plateau and the posterior cartilage was intact. The site of the lesion and the intact state of the cruciate ligaments taken together explain why varus deformity was observed only in the extended knee, and why the deformity was correctable and had not become fixed. Failure of the anterior cruciate ligament may allow the erosion to extend posteriorly, producing fixed varus deformity and leading to degeneration of the lateral compartment. Anteromedial osteoarthritis is a distinct clinicopathological entity; its radiographic features enable it to be diagnosed from lateral radiographs; its anatomical features render it suitable for treatment by unicompartmental arthroplasty

We have tested the reliability of a recently reported classification system of hip morphology in adolescents with cerebral palsy in whom the triradiate cartilage was closed. The classification is a six-grade ordinal scale, based on the measurement of the migration percentage and an assessment of Shenton’s arch, deformity of the femoral head, acetabular deformity and pelvic obliquity. Four paediatric orthopaedic surgeons and four physiotherapists received training in the use of the classification which they applied to the assessment of 42 hip radiographs, read on two separate occasions. The inter- and intra-observer reliability was assessed using the intraclass correlation coefficient and found to be excellent, with it ranging from 0.88 to 0.94. The classification in our study was shown to be valid (based on migration percentage), and reliable. As a result we believe that it can now be used in studies describing the natural history of hip displacement in cerebral palsy, in outcome studies and in communication between clinicians

Destruction of the articular cartilage is the first change seen on gross examination of the knee in osteoarthritis. Weight-bearing radiographs are conventionally taken with the knee in full extension. Biomechanical studies have shown, however, that the major contact stresses in the femorotibial articulation occur when the knee is flexed about 28 degrees. Arthroscopy has confirmed that cartilage loss occurs in a more posterior portion of the femoral condyles than is revealed by radiographs taken in full extension. The 'standing tunnel view' is a weight-bearing postero-anterior radiograph taken with the knee in 30 degrees of flexion. The radiographs of 64 patients have been used to compare the conventional with the standing tunnel view. In 10 knees in which the conventional view suggested normal cartilage the standing tunnel view revealed severe degeneration

In 16 cadaver humeroulnar joints, the distribution of subchondral mineralisation was assessed by CT osteoabsorptiometry and the position and size of the contact areas by polyether casting under loads of 10 N to 1280 N. Ulnas with separate olecranon and coronoid cartilaginous surfaces showed matching bicentric patterns of mineralisation. Under small loads there were separate contact areas on the olecranon and coronoid surfaces; these areas merged centrally as the load increased. They occupied as little as 9% of the total articular surface at 10 N and up to 73% at 1280 N. Ulnas with continuous cartilaginous surfaces also had density patterns with two maxima but those were less prominent, and in these specimens the separate contact areas merged at lower loads. The findings indicate a physiological incongruity of the articular surfaces which may serve to optimise the distribution of stress

We studied the early cartilage changes in osteoarthritis, examining the most normal appearing articular cartilage from the hips of 17 patients. Normal appearing cartilage from five patients treated for fractures was used as control material. Two different types of clone were found. The first had increased staining for proteoglycan and was thought to have been engaged in the synthesis of matrix. The other type was associated with a severe deficiency of proteoglycan, matrix streaks and evidence of degradation and phagocytosis of matrix components. Immunohistochemistry demonstrated large amounts of chondroitin 4 and 6 sulphate about the synthetic-type clones, and little or no reactivity about the degenerative clones which lay more superficially and were associated with matrix destruction. Clones appeared to be engaged in either matrix synthesis or its destruction. The disease process of osteoarthritis appeared to begin at the surface of the articular cartilage

The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair

We report the results of arthroscopic removal of loose bodies and abnormal synovium from 18 knees with primary synovial chondromatosis. After a mean of three years, six months (range one to 10 years), 14 knees were either symptom-free or had only minor symptoms. Three of these had required two arthroscopic operations. Three patients were improved but not cured and there was one failure. The results were better than the published results of open operation for this condition. Three patterns of macroscopic appearances were noted: four knees had large lesions covered by normal synovium, 10 had small fragments of cartilage lying in or on the synovium and four had only free fragments of cartilage in the joint cavity but none in, on, or under, the synovium. These three appearances may represent three different disease processes

We have compared, in rabbits, two techniques of limb lengthening by distraction of the epiphyseal plate using a unilateral external fixation frame. In all cases, 14 mm of symmetrical lengthening without deviation was achieved. With rapid distraction at rates of 1 mm per day (distractional epiphyseolysis) separation of the epiphysis from the metaphysis occurred by day 7, and by day 70 almost complete ossification of the cartilage and the elongated segment was evident. In contrast, slow distraction at 0.25 mm every 12 hours (chondrodiatasis) produced hyperplasia of growth cartilage without any evidence of detachment at 28 days, the end of the distraction period. By day 70 the epiphyseal plate had returned to normal thickness with normal cellular morphology, while the lengthened segment was occupied by ossified tissue. The significance of these findings is discussed