Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats. Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture. Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue. Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair

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

In this study we evaluated whether the Instability Severity Index Score (ISIS) and the Western Ontario Shoulder Instability Index (WOSI) could detect those patients at risk of failure following arthroscopic Bankart repair. Between April 2008 and June 2010, the ISIS and WOSI were recorded pre-operatively in 110 patients (87 male, 79%) with a mean age of 25.1 years (16 to 61) who underwent this procedure for recurrent anterior glenohumeral instability. . A telephone interview was performed two-years post-operatively to determine whether patients had experienced a recurrent dislocation and whether they had returned to pre-injury activity levels. In all, six (5%) patients had an ISIS > 6 points (0 to 9). Of 100 (91%) patients available two years post-operatively, six (6%) had a recurrent dislocation, and 28 (28%) did not return to pre-injury activity. No patient who dislocated had an ISIS > 6 (p = 1.0). There was no difference in the mean pre-operative WOSI in those who had a re-dislocation and those who did not (p = 0.99). The pre-operative WOSI was significantly lower (p = 0.02) in those who did not return to pre-injury activity, whereas the ISIS was not associated with return to pre-injury activity (p = 0.13). . In conclusion, neither the pre-operative ISIS nor WOSI predicted recurrent dislocation within two years of arthroscopic Bankart repair. Patients with a lower pre-operative WOSI were less likely to return to pre-injury activity. Cite this article: Bone Joint J 2014; 96-B:1688–92

Objectives. Previously, we reported the improved transfection efficiency of a plasmid DNA-chitosan (pDNA-CS) complex using a phosphorylatable nuclear localization signal-linked nucleic kinase substrate short peptide (pNNS) conjugated to chitosan (pNNS-CS). This study investigated the effects of pNNS-CS-mediated miR-140 and interleukin-1 receptor antagonist protein (IL-1Ra) gene transfection both in rabbit chondrocytes and a cartilage defect model. Methods. The pBudCE4.1-miR-140, pBudCE4.1-IL-1Ra, and negative control pBudCE4.1 plasmids were constructed and combined with pNNS-CS to form pDNA/pNNS-CS complexes. These complexes were transfected into chondrocytes or injected into the knee joint cavity. Results. High IL-1Ra and miR-140 expression levels were detected both in vitro and in vivo. In vitro, compared with the pBudCE4.1 group, the transgenic group presented with significantly increased chondrocyte proliferation and glycosaminoglycan (GAG) synthesis, as well as increased collagen type II alpha 1 chain (COL2A1), aggrecan (ACAN), and TIMP metallopeptidase inhibitor 1 (TIMP-1) levels. Nitric oxide (NO) synthesis was reduced, as were a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS-5) and matrix metalloproteinase (MMP)-13 levels. In vivo, the exogenous genes reduced the synovial fluid GAG and NO concentrations and the ADAMTS-5 and MMP-13 levels in cartilage. In contrast, COL2A1, ACAN, and TIMP-1 levels were increased, and the cartilage Mankin score was decreased in the transgenic group compared with the pBudCE4.1 group. Double gene combination produced greater efficacies than each single gene, both in vitro and in vivo. Conclusion. This study suggests that pNNS-CS is a good candidate for treating cartilage defects via gene therapy, and that IL-1Ra in combination with miR-140 produces promising biological effects on cartilage defects. Cite this article: R. Zhao, S. Wang, L. Jia, Q. Li, J. Qiao, X. Peng. Interleukin-1 receptor antagonist protein (IL-1Ra) and miR-140 overexpression via pNNS-conjugated chitosan-mediated gene transfer enhances the repair of full-thickness cartilage defects in a rabbit model. Bone Joint Res 2019;8:165–178. DOI: 10.1302/2046-3758.83.BJR-2018-0222.R1

Introduction

Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair.

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT

Using 26 cadaver shoulders, we produced a standard defect in the supraspinatus tendon and performed one of three types of repair. Their strength was found by testing in tension the force required to produce a gap of 3 mm, then 6 mm, and finally total disruption of the repair. The use of a polyethylene patch to spread the forces over the lateral bone surface and of extra sutures to grasp the tendon end raised by 2.6 times the load at which a 3 mm gap in the repair occurred and by 1.7 times the load to failure

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1. +/−. ) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1. +/−. mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1

We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years (. sd. 0.4). Cox’s proportional hazards model was used to assess the effect of covariates on survival, with age at the time of surgery (p = 0.026) and number of previous operations (p = 0.006) found to be significant. The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial versus lateral allograft transplantation. Patients experienced significant improvements at all periods of follow-up in subjective outcome measures of pain, activity and function (all p-values < 0.05), with the exception of the seven-year Tegner index score (p = 0.076)

Aims

Optimal exposure through the direct anterior approach (DAA) for total hip arthroplasty (THA) conducted on a regular operating theatre table is achieved with a standardized capsular releasing sequence in which the anterior capsule can be preserved or resected. We hypothesized that clinical outcomes and implant positioning would not be different in case a capsular sparing (CS) technique would be compared to capsular resection (CR).

The tensile strength of the medial patellofemoral ligament (MPFL), and of surgical procedures which reconstitute it, are unknown. Ten fresh cadaver knees were prepared by isolating the patella, leaving only the MPFL as its attachment to the medial femoral condyle. The MPFL was either repaired by using a Kessler suture or reconstructed using either bone anchors or one of two tendon grafting techniques. The tensile strength and the displacement to peak force of the MPFL were then measured using an Instron materials-testing machine. The MPFL was found to have a mean tensile strength of 208 N (SD 90) at 26 mm (SD 7) of displacement. The strengths of the other techniques were: sutures alone, 37 N (SD 27); bone anchors plus sutures, 142 N (SD 39); blind-tunnel tendon graft, 126 N (SD 21); and through-tunnel tendon graft, 195 N (SD 66). The last was not significantly weaker than the MPFL itself

The management of traumatic dislocation of the knee in 40 patients (41 knees) with a mean age of 26.3 years is described. They were treated by primary repair and reconstruction with autologous grafting of the anterior (ACL) and posterior cruciate ligaments (PCL) and repair injuries to the collateral ligament and soft-tissue. The ACL and PCL were reconstructed using the patellar tendon and the gracilis and semitendinosus tendons, respectively. Early mobilisation using a continuous-passive-movement machine and active exercises was started on the second day after operation. At a mean follow-up of 39 months no patient reported ‘giving way’ and all except one had good range of movement. Of the 41 knees, 21 were rated as excellent, 15 good, four fair and one poor. Early reconstruction of the cruciate ligaments and primary repair of the collateral ligaments followed by an aggressive rehabilitation programme are recommended for these young, active patients

A dural tear is a common but troublesome complication of endoscopic spinal surgery. The limitations of space make repair difficult, and it is often necessary to proceed to an open operation to suture the dura in order to prevent leakage of cerebrospinal fluid. We describe a new patch technique in which a small piece of polyglactin 910 is fixed to the injured dura with fibrin glue. Three pieces are generally required to obtain a watertight closure after lavage with saline. We have applied this technique in seven cases. All recovered well with no adverse effects. MRI showed no sign of leakage of cerebrospinal fluid

1. The use of a protein-free synthetic medium has provided a new technical approach to the study of fracture healing in vitro. 2. The tibiae of fourteen-day embryonic chicks were cut in half in the middle of the shaft, the fragments were placed in apposition and the explants grown in vitro for up to sixteen days. The process of bone repair was studied by means of histology and biochemical estimations. 3. The rate of growth in length of fractured bones was greater in an atmosphere containing 50 per cent of oxygen than in one with 20 per cent oxygen, thus emphasising the importance of an adequate oxygen supply for the regeneration of osteogenic cells. 4. The effect of varying the concentration of glucose in the medium was investigated. Two milligrams of glucose per millilitre was the most favourable for healing; higher levels caused fibroblastic changes in the cartilage cells and inhibited the proliferation of osteogenic cells at the fracture site. 5. Histological examination showed that many of the phenomena that occur in the repair of fractures in vivo can be reproduced in vitro in synthetic medium. Similar results were obtained whether the fracture was made in whole bones or in isolated shafts from which the cartilaginous ends had been removed; the latter are more favourable for biochemical study

Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period, using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle. Review of these patients showed that poor results were associated with larger cuff defects, with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle. A randomised prospective study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side. Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ. Follow-up showed that the results continued to improve for two years after operation; their quality was maintained in patients less than 60 years old, but in those over 60 there was deterioration with time

We randomised 50 patients with ankle fractures of Weber types B and C and a ruptured deltoid ligament treated by open reduction and internal fixation to two treatment groups to examine the influence of the repair of a ruptured deltoid ligament. No differences were found except for a longer duration of surgery in the repair group. Our findings suggest that a ruptured deltoid ligament can be left unexplored without any effect either on early mobilisation or on the long-term result

From 1986 to 1993, we repaired 278 torn menisci in 264 patients using an arthroscopically assisted inside-out technique. A total of 132 meniscal repairs in 122 patients were evaluated by second-look arthroscopy. At review, only nine patients had meniscal symptoms, such as locking, swelling or pain. Ninety-seven menisci (73%) had healed completely at the repair site, but there were new tears in different areas of 21 menisci, some of which had complete healing at the repair site. Incomplete healing, seen in 23 menisci (17%), was frequently near the popliteus tendon, most commonly where there had been an associated anterior-cruciate-ligament injury. Arthroscopically-assisted meniscal repair seems to be a reliable procedure, but some clinically successful cases had incomplete healing at the repair site or a newly-formed tear in the meniscal body or both. These lesions may cause meniscal symptoms to appear at a later date

We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff. We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity. Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients

Between 1979 and 1989, we treated 22 patients with symptomatic lumbar spondylolysis which had not responded to conservative treatment by a modified Scott wiring technique to give direct repair of the lytic defects with stabilisation. The patients' mean age at the time of operation was 15 years; the mean follow-up period was four years. All 19 patients under 25 years old had satisfactory results. Two of the three patients over 25 years old had poor results. The age of the patient at surgery seems to be an important determinant of outcome. Radiologically confirmed fusion is of secondary importance. The presence of a grade I spondylolisthesis did not prejudice the result. We recommend the Scott wiring technique to stabilise the direct repair of a lumbar spondylolysis

We examined biopsy specimens obtained during surgery on 115 patients with complete rotator cuff rupture. The vascularised connective tissue covering the area of rupture and the proliferating cells in the fragmented tendons reflected more of the features of repair than of degeneration and necrosis. The main source of this fibrovascular tissue was the wall of the subacromial bursa. These features clearly indicated a vigorous reparative response which might play an important role in tendon reconstitution and remodelling. We therefore suggest that extensive debridement along with subtotal bursectomy, commonly practised during surgical repair of rotator cuff rupture, should be avoided. Although strong suture margins are essential for good operative results, debridement should be judicious and preserve as much as possible of the bursa and the associated fibrovascular tissue