Metal-on-metal (MOM) hip resurfacings release chromium and cobalt wear debris into the surrounding joint. The hip tissue taken from failed MOM hips shows specific histological features including a subsurface band-like infiltrate of macrophages with particulate inclusions, perivascular lymphocytic infiltrate and fibrin exudation. This tissue response has been called Aseptic Lymphocytic Vasculitis Associated Lesion (ALVAL).

There is a recognised carcinogenic potential associated with hexavalent chromium and epidemiological data from first generation MOM arthroplasties may suggest an increased incidence of haematological malignancy. The ALVAL type reaction includes a marked proliferation of lymphocytes in the perivascular space and thorough investigation of this lymphocytic response is warranted.

This study aims to further characterise the lymphocytic infiltrate using immunohistochemistry and to test clonality using polymerase chain reaction (PCR).

Tissues from revised all cause failed MOM hip arthroplasties (n=77) were collected and analysed initially using routine H&E staining. Those that met the diagnostic criteria of ALVAL described above (n=34) were further stained with a panel of immunohistochemical markers (CD3, CD4, CD8 (T-cell markers) and CD20 (B-cell marker)). 10 representative ALVAL cases were selected and sent for gene rearrangement studies using PCR to determine whether the lymphocytes were polyclonal or monoclonal in nature.

The analysis of the lymphocytic aggregates in ALVAL, showed a mixed population of B and T cells. Within the aggregates, there was a predominance of B cells (CD20) over T cells (CD3). Of the 10 cases which were analysed by PCR, 7 were suitable for interpretation. None of these cases showed evidence of monoclonal lymphocyte proliferation.

The carcinogenic potential of wear debris from MOM hips, particularly affecting the haematopoietic system should be investigated. This study has shown a predominantly B-lymphocyte response in tissues surrounding MOM hips which is polyclonal. Although the numbers are small, the study suggests an immune mediated response in MOM hip tissue and excludes a neoplastic proliferation.

However, long term follow up of patients with MOM hips may be prudent.

Introduction: Approximately 0.5 % of patients with metal on metal hip replacements develop post operative pain which is thought to be due to an immune reaction to metal wear particles, known as Aseptic Lymphocyte Dominated Vasculitis Associated Lesion (ALVAL). Treatment usually requires revision to a non metal on metal hip.. Is the development of ALVAL more likely in those patients with high wear rates?

Methods: Retrieved Metal on Metal (MOM) hip implants; periprosthetic tissue and blood samples were obtained from patients (n = 18) undergoing revision for unexplained pain at a mean of 2 years post operatively. The following variables were measured:

linear wear rate (depth of the femoral head and acetabular socket wear patch/time from operation);

All implants and tissue samples were analysed against control samples from patients undergoing revision of MOM hips for fractured femoral neck or impingement.

Results: Linear wear rates of retrieved implants, and blood levels of cobalt and chromium from patients with unexplained plain were greater than from control patients. Histolopathological analysis of tissue showed dense inflammatory infiltrates with healthy looking endothelial cells in all vessels from both patient groups.

Discussion and Conclusion: A painful MOM hip was associated with high wear rates and blood metal levels. The local inflammatory response was similar to “ALVAL”, ie lymphocyte dominated, but not exclusive to those patients with unexplained pain. We question whether ALVAL represents a vasculitis, or merely a classical lymphocyte driven inflammatory tissue response to metal debris particles.

The purpose of this study was to determine and compare the effects of radiofrequency ablation and mechanical shaving on tendon using histological and ultrastructural techniques. A single cut using a scalpel blade was used to create a standardised reproducible lesion in 12 freshly harvested ovine infraspinatus tendons. Each lesion was then subjected to either bipolar radiofrequency ablation or mechanical shaving. Specimens were either fixed in formalin and processed for light microscopy or fixed in glutaraldehyde and processed for transmission electron microscopy. Samples of normal and untreated cut tendon were analysed as suitable controls. The radiofrequency treated samples showed an area of coagulative necrosis with an average diameter of 2mm around the lesion. Conversely, the shaved samples showed viable cells up to the edges of the lesion. These findings were supported by ultrastructural appearances, which showed preservation of tendon architecture in shaved samples and widespread denaturation of the tendon matrix with loss of fibrillar structure in the radiofrequency treated samples. Radio-frequency electrical energy and mechanical shaving are often used for resection of soft tissues during arthroscopic reconstructive procedures. The effects of these techniques on tendon are not yet clearly understood. The results of this study indicate that thermal resection of tendon causes an immediate additional 2mm area of tissue necrosis which is not present after mechanical shaving. These findings may have implications for the success of arthroscopic debridement and tendon repair procedures.

Introduction and Aims: We have developed a novel murine open tibial fracture model to compare the vascularity of muscle and fasciocutaneous flaps during fracture healing and investigate their role in angiogenesis.

Method: Flaps were emulated by insertion of a piece of sterile, inert material (Polytetrafluoroethylene, PTFE), at the fracture site to exclude either muscle posteriorly (fasciocutaneous flap) or skin and fascia anteriorly (muscle flap). Animals were harvested at days three, five, seven, nine and 14 post-fracture. Immunohistochemistry was performed on specimens, to estimate vascularity using an antibody to factor VIII, which selectively demonstrates vascular endothelium. Vascular densities were determined within the muscle and fasciocutaneous tissues adjacent to the fracture sites. Vascular Endothelial Growth Factor (VEGF) was measured by ELISA in tissue specimens. Immunohistochemistry was performed to qualitatively assess distribution of VEGF.

Results: Significantly greater vascular densities per unit area were observed in fasciocutaneous flaps at all time points compared to muscle flaps (p< 0.0001). VEGF levels peaked at day seven post-fracture, fell at day nine, and increased again at day 14. This time-dependent variation was statistically significant (p< 0.02). However, there was no significant difference between muscle and fasciocutaneous flaps. Maximal staining for VEGF occurred on the deep surface of the flaps adjacent to the fracture site. We found that fasciocutaneous flaps have significantly higher vascular densities compared to muscle flaps during early fracture healing.

Conclusion: Our results contradict the widely held view that muscle flaps are superior. However, there was no significant difference between levels of the pro-angiogenic factor VEGF within the flaps. This would suggest that both flaps are equally effective in supplying the factors necessary for new vessel formation. Our data supports the continuing use of muscle and fasciocutaneous flaps in the clinical setting.

Vascular Endothelial Growth Factor (VEGF) has been shown to stimulate angiogenesis in a number of tissues and, in addition, to possess direct vasoactive properties. Stimulation of blood flow and angiogenesis are important features of the fracture healing process, particular in the early phases of healing. Inadequate vascularity has been associated with delayed union after fracture. The periosteum, and in particular its osteogenic cambial layer, has been shown to be very reactive to fracture and to contribute substantially to fracture healing. Fracture haematoma contains a considerable concentration of VEGF and enhanced plasma levels are observed in patients with multiple trauma. VEGF has been suggested to play a role during new bone formation possibly providing an important link between hypertrophic cartilage, angiogenesis and consequent ossification. However, the expression of VEGF in normal periosteum and in periosteum close to a fracture has not been previously reported. We hypothesise that the expression of VEGF in long bone periosteum will show a distinct response to fracture.

We investigated the expression of VEGF in vivo in human periosteum, using immunocytochemistry to detect the expression of Factor VIII and VEGF protein respectively. Under prior approval from the local Ethics Committee, biopsies of periosteal tissues were collected from two distinct groups (1) control and (2) following long bone fracture. Patient age range was 16 – 45 years for both groups. Group 1 consisted of patients (n = 5) who underwent an elective orthopaedic procedure during which periosteum was disrupted. Group 2 patients (n = 8) had long bone fractures from which periosteal tissue was harvested close to the fracture site during internal fixation at various time points following fracture (24 hours to nine days).

In Group 1 the periosteum showed abundant but delicate blood vessels staining throughout for VEGF but there was no other visible staining of other structures or cells. In Group 2 the vasculature in the periosteum close to the fracture site demonstrated a characteristic, time-dependent course of expression of VEGF. At 24 and 48h following fracture the vasculature showed a heterogenous picture. The vessels in periosteum showed signs of activation: thickened endothelia and dilated lumina, but did not express VEGF. At 60h the vessels began to show signs of the presence of VEGF protein and by 4 days most periosteal vessels expressed VEGF. Also at this time, VEGF staining was visible in some of the stromal cells of the periosteum that was not seen in any of the earlier times. At 9 days VEGF was visible not only in the omnipresent vasculature, but now consistently in spindle shaped cells of fibroblastic appearance and chondrocytes throughout the early callus.

This study, though limited by the number of patients, shows for the first time the expression of VEGF in normal periosteum as well as in periosteum during fracture healing. Interestingly, activated vessels in the early healing phase show little expression of VEGF; however it is known that the fracture haematoma contains VEGF in abundance. It is possible that the vasoactive role of VEGF prevails in these early days. There may be a critical time point at around 48h post fracture following which angiogenesis begins and VEGF is expressed in the endothelium throughout the vessel wall. The study suggests an important role for VEGF in the regulation of fracture healing. VEGF is not only expressed in endothelial cells within the periosteum but also in fibroblast-like stem cells and chondrocytes throughout the early callus suggesting it may play an important role in both osteo- and angiogenesis

Radio frequency (RF) electrothermal capsulorrhaphy has potential to enhance the results of arthroscopic stabilisation. However, early clinical reports have shown variable results when compared with open stabilisation. Numerous experiments have shown that the mechanical properties of thermally treated tissue are mechanically inferior to normal tissue during the early phase of remodelling. Ultimately, the real issue is how thermally treated tissue compares with tissue shortened by surgical plication, as would occur in an open procedure.

Using a validated technique the tibial insertion of the medial collateral ligament (MCL) of the knee was shifted proximally to induce abnormal laxity in 30 mature NZ White rabbits. Bipolar RF shrinkage was applied to the MCL in 15 rabbits, while in the remainder the MCL was surgically transected and plicated with a nonabsorbable suture. Unlimited mobilisation was permitted until euthanasia at 12 weeks after surgery. Bone-ligament-bone complexes were harvested and underwent low-load (viscoelastic) and high-load (tensile failure) analysis on an Instron mechanical testing apparatus. Specimens from intact MCLs were also collected for polarised light microscopy and transmission electron micrography. Quantitative analysis of collagen fibril morphology was performed on the TEM images.

There were no significant complications postoperatively. In both groups there was evidence of ligament healing and remodelling with a thin layer of scar tissue surrounding the MCL. Preliminary analysis has demonstrated that the cross-sectional area of the thermally treated MCLs was increased compared with the plicated MCLs. Somewhat surprisingly, the plicated group had greater vascularity and cellularity in the healing zone than the thermal group. Although crimp patterns remained disorganised in both groups, the collagen matrix appeared more organised in the thermal group.

These results support the concept that the thermally denatured matrix may act as a scaffold for rapid remodelling of the MCL, resulting in a larger mass of ‘scar’ tissue at the site of shrinkage. Since scar tissue following surgical transection is known to be materially inferior to normal ligament tissue, the increased volume in the thermal group may confer an advantage in structural terms. Mechanical testing is presently underway in our laboratory to determine this issue.