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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIX | Pages 41 - 41
1 Jul 2012
London N Smith J Guy S Hayes D Waller C Williams R
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Statement of Purpose

The UK and Australian clinical experience of an implantable load absorber was reviewed for knee OA patients who have exhausted conservative care, but are not ideal candidates for HTO or arthroplasty due to age, activity level, obesity, or disinclination.

Methods and Results

The load absorber was implanted in 58 patients, with the longest duration exceeding two years. Patients included younger OA sufferers (31-68 years), and had a mean BMI > 30kg/m2. Early surgical experience and adverse events with the device were recorded and clinical outcomes using validated patient reported outcomes tools were collected at baseline, post-op, 2 and 6 weeks, and 3, 6, 12 and 24 month timepoints.

All patients were successfully implanted with a mean surgical time of 76.4 minutes (range 54-153). After a mean hospital stay of 1.7 days (range 1-3), patients resumed full weight bearing within 1-2 weeks and achieved normal range of motion by 6 weeks. Mean WOMAC pain (0-100 scale) improved from 42.4 to 16.1 (p<0.001); mean WOMAC function (0-100 scale) improved from 42.0 to 14.7 (p<0.001). Most patients reported “no or mild” pain (85%) or “no or mild” functional impairment (90%) at last follow-up (9.5 ± 3.5 months). Patients reported high satisfaction with the implant. Initial UK results mirror the positive Australian experience: reduced pain, improved function, and high satisfaction.

Complications arising in the early surgical experience were effectively resolved through revised surgical technique and minor design modifications.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIX | Pages 17 - 17
1 Jul 2012
Rath N Bewick A Williams R Wilson C White S Forster M
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Background

Patellofemoral replacement is an established intervention in selected patients with severe isolated patellofemoral osteoarthritis. FPV (Wright Medical, UK) is a third generation patellofemoral arthroplasty implant and is the second most used after AVON in National Joint Registry for England and Wales. Reports of survivorship and functional of this implant are scarce in literature.

Aim

Evaluation of functional outcome and survivorship following FPV patellofemoral arthroplasty.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIX | Pages 87 - 87
1 Jul 2012
Williams R Khan I Richardson K Nelson L McCarthy H Dowthwaite G Lewis H Baird D Dudhia J Robinson R Shaw H Singhrao S Alnabelsi T Roberts S Briggs T Fairclough J Archer C
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Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [Dowthwaite et al, 2004, J Cell Sci 117;889], they can be expanded to generate hundreds of millions of cells, produce hyaline cartilage and they have a restricted differential potential. Articular chondroprogenitors do not readily terminally differentiate down the osteogenic lineage.

At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded in vitro to a high population doubling whilst maintaining a normal karyotype. Articular cartilage progenitors maintain telomerase activity and telomere length that are a characteristic of progenitor/stem cells and differentiate to produce hyaline cartilage.

In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIX | Pages 103 - 103
1 Jul 2012
Zourelidis C Mukhopadhyay S Kotwal R Williams R
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In recent years tribological development of knee replacement impants has beeen introduced with several benefits. However, concomitant problems were noticed following widespread use.

High-flexion total knee replacement (PFC RPF DePuy) has been developed with a view to improve flexion and the design is expected to have a better patello-femoral biomechanics. However, high secondary patella resurfacing rate has been noticed in the current series.

We have retrospectively reviewed 119 knees in 96 patients who underwent RPF knee replacement with selective patellar resurfacing from 2006 to 2010 by the senior author. 71 were performed without primary resurfacing while 48 in knees patella was resurfaced primarily due to significant symptomatic arthritic changes. Majority were females (57 versus 39 males). Average follow-up period was 37 (12-62) months.

Twelve (16.9%) knees were subjected to secondary resurfacing due to continuing anterior knee pain. Average time from primary total knee replacement to secondary resurfacing was 18 months (8-35). Most of the patients were satisfied following the secondary resurfacing.

Mean Oxford Knee Score in the group where the patella was resurfaced primarily was 33.1 (9-48), in the group where the patella was not resurfaced 32.8 (11-47), in the secondary resurfacing group 31.8 (14-43) and in the revision group 20.5 (16-25).

RPF knee replacements in our series have a considerably higher rate of secondary patellar resurfacing as compared with published literature. We recommend primary patellar resurfacing of all RPF knee replacements to avoid this problem. Further analysis of the prosthetic design would be beneficial in relation to clinical outcome.

No of patients-96

Total no of knee-118

Av age-66.5

Females-57

Males-39

Patella not resurfaced- 73

Resurfaced-45

Revised-10(13.7%)

Revision to TKR (TC3) for different reason-3(2.54%)

Average time from primary to secondary resurfacing-


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 37 - 37
1 May 2012
Kotwal RS Brakspear K Roberts H Wilson C Williams R Sultan J Mason DJ
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Glutamate is a neurotransmitter that transmits mechanical signals in bone (1) and activates glutamate receptors and transporters, in bone, cartilage, meniscus and synovium (2). Glutamate receptor activation influences inflammatory, degenerative and nociceptive pathways in arthritic joints (2). Thus glutamate signalling is a mechanism whereby mechanical load can directly influence joint pathology and pain. We have investigated components of glutamate signalling in the subchondral bone of patients with osteoarthritis to determine which are expressed and whether this varies in anatomical regions subject to different loads. Subchondral bone was sampled from tibial cuts derived from total knee arthroplasty (n=2, TKR, Kellgren Lawrence grade 3) and from tibial drill hole sites from high tibial osteotomy (n=5, HTO, KL grades 2 and 3) for osteoarthritis. RNA was extracted, reverse transcribed and RT-PCR performed for a housekeeping gene GAPDH, a glutamate transporters (EAAT-1, EAAT1ex9skip), glutamate receptors (NR2A and KA1), a bone matrix protein, osteocalcin, and signaling molecules (osteoprotegerin [OPG], RANKL). We found differential mRNA expression in different regions of subchondral bone. In one TKR patient, EAAT-1 expression was significantly reduced in the anterior zone versus the middle or posterior zones of the tibial plateau (ANOVA, p<0.001). HTO bone cores were subdivided medial/lateral and anterior/posterior. Good quality RNA was obtained from bone cores removed from drill holes during HTO surgery, with GAPDH, osteocalcin, EAAT-1, EAAT1ex9skip, NR2A, KA1, OPG and RANKL mRNA expression detected. In one patient, comparison of gene expression in bone cores obtained pre and post HTO revealed that EAAT1ex9skip was rarely detected in post-op bone whereas KA1 was rare in pre-op bone. This differential mRNA expression may be due to the altered loading through the joint caused by the osteotomy, although these on/off differences need to be quantified to confirm this.

We have shown that glutamate transporters and receptors are expressed in human subchondral bone. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate released in arthritis will influence pathological changes and nociception. In some patients, glutamate transporter mRNA expression appears to vary with anatomical location in bone, or after HTO surgery, consistent with our original discovery of this transporter as mechanically-regulated in bone (1). If glutamatergic signaling is mechanically regulated in the human knee, this will vary during arthritic disease progression and after joint realignment, providing a direct mechanism linking mechanical loading through the joint to pathology and pain in arthritis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 171 - 171
1 May 2012
Williams R
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The simple dictum of the late Prof. Alf Nachemson was that ‘surgery should very rarely, if ever, be performed in adult scoliotic patients for lumbar curves when pain is the most serious problem’. Today, the complexity of intercurrent neural symptoms, the advancing age of the population and the increasing demands and expectations of modern living require a somewhat more flexible approach to this increasingly common problem.

Treatment of adult deformity has improved along with our understanding of the radiological features of the condition most likely to be associated with disabling pain and also with our appreciation of the adverse significance of patient co-morbidity. In those patients where conservative measures have failed and where an acceptable quality of life has been lost, surgical management may be undertaken, but must address all the symptomatic aspects of the deformity in one episode of care.

Primary objectives include the restoration of satisfactory sagittal plane correction using the minimum number of operated levels whilst providing adequate spinal stability. Meticulous preoperative planning from a clinical and radiological perspective maximises the possibility of a satisfactory outcome and in this regard patient expectation is of prime importance. The questions of operative approach and levels of fixation are ever present and recent advances in our understanding of distal end fixation are worthy of consideration.

Finally, exemplary cases and our series of 23 patients undergoing surgical treatment of adult scoliosis will be presented. Mean coronal curve correction by anteroposterior approach was 60.4% and by posterior only approach 40.3%.

Patient satisfaction was 77.8% by combined approach and 58.9% by posterior only approach. The rate of reoperation was 66.7% for posterior surgery alone and 11.1% for combined approach corrections.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 108 - 108
1 Apr 2012
Gibson A Mehta S Goss B Williams R
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Tapping the radial side of the wrist normally elicits a reflex contraction producing elbow flexion, wrist extension and wrist radial deviation. An abnormal response, consisting of finger flexion when performing this manoeuvre is known as the inverted radial (supinator) reflex (IRR). The significance of this reflex in asymptomatic subjects is unknown.

To document the frequency of the IRR in an asymptomatic population and to identify any presymptomatic pathology in those subjects.

The study group consisted of patients and staff at the senior author's institution. Patients were taken from clinics where the complaints were of lower limb symptoms. Subjects were excluded if they had any history of neck pain or stiffness or if they had any subjectively abnormal sensation. The radial reflex was elicited with a tendon hammer. Those subjects with an IRR were asked to attend for a MRI scan of the cervical spine to investigate for any abnormality.

47 subjects were studied. There were 8 subjects who displayed an IRR. In 4 subjects the IRR was unilateral and in 4 bilateral. Seven subjects consented to further investigation by MRI. The average age of these patients was 36 years.

The MRI scans revealed normal appearances in 6 cases. There was no cord signal abnormality in any case.

The IRR occurred with a frequency of 17% in the study group. There was no significant cervical pathology identified in these subjects.

In young asymptomatic patients, the presence of an inverted radial reflex is of no diagnostic relevance.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 110 - 110
1 Apr 2012
Young Y Gibson A Lutton C Mackay-Sim A Mehta S Williams R Goss B
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AO Spine Reference Centre & Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

Traumatic spinal cord injury (SCI) is a devastating condition with no curative therapy. Pro-inflammatory therapy has been suggested recently to try and reduce the inhibitory glial scar and promote neural regeneration and healing. The aim of this study is to investigate the potential of sustained delivery of angiogenic/pro-inflammatory growth factors to reduce the secondary degeneration after spinal cord injury.

Adult male Wistar Kyoto rats (200-300g; 12-16weeks old) were subjected to cord hemisections via a T10 laminectomy. Animals were randomised to treatment or control groups after the spinal cord injury had been induced. Treatment consisted of implantation of a mini-osmotic pump capable of delivering 5 micrograms vascular endothelial growth factor (VEGF) and 5 micrograms platelet-derived growth factor (PDGF), via a catheter, to the site of the lesion, over 7 days(n=6). Control animals were subjected to either cord lesion only (n=6) or lesion plus mini-pump delivering PBS (phosphate-buffered saline) solution (n=6). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200 and anti-Glial Acidic Fibrillary Acidic Protein (GFAP) antibodies.

RESULTS: Active treatment spinal cords showed a higher level with aboration of the axonal filament through the defect and more dense neurofilament-200 staining at the lesion site compared to both control groups. The treatment also showed the elevated presence of activated microglia in the lesion, whilst distal to the lesion the microglia and astrocytes retained an unreactive phenotype.

Pro-inflammatory therapy in the rat spinal cord-injury model showed favourable histological findings after sustained delivery of PDGF and VEGF


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 483 - 483
1 Nov 2011
Fazal M Williams R
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Purpose: We conducted a study of 72 hammer toes treated with proximal interphalangaeal joint (PIPJ) fusions with a Stayfuse implant. The aim of the study was to access the clinical results of PIPJ fusion carried out with Stayfuse implants.

Method: There were 10 males and 62 females. Average age was 52 years. Twelve cases had bilateral and 60 cases had unilateral foot involvement. Fifty-two second and 20 third toes were operated on. Mean follow up was twelve months. The results were assessed clinically, radiologically and with the American orthopaedic foot and ankle surgery society (AOFAS) score.

Results: All the joints fused clinically except two. There were ten PIPJ’s which did not fuse radiologically. The AOFAS score improved from 42 preoperativley to 84 post operatively. There were two cortical breeches of the proximal phalanx, one implant breakage and one case of dissociation of the components of the implant at six weeks after the surgery, with a recurrence of deformity. There were two patients who complained of over-straight toes. Fifty-two patients were very satisfied with the procedure, seventeen satisfied and three patients were unsatisfied.

Conclusion: We conclude that the Stayfuse is safe, reliable method to correct PIPJ deformity, although there is a learning curve. The main advantages of the implant are that there is no postoperative implant exposure, no violation of healthy joints, no risk of pin tract infection, rotational and angular stability, early rehabilitation and a high patient satisfaction. The disadvantages of the implant are dissociation of the components and the difficulty of removal, if this is needed.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 187 - 187
1 May 2011
Ferran N Hodgeson P Vannet N Williams R Evans R
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We undertook a prospective randomised trial to determine the outcome of locked intramedullary fixation vs. plating of displaced shortened mid-shaft clavicle fractures. The primary outcome measure was the Constant shoulder score, while secondary outcome measures included the Oxford shoulder score, union rate, and complication rates.

Thirty-two patients were recruited to the trial; 17 randomised to locked intramedullary fixation and 15 randomised to plating. Mean age was 29.3years (13 to 53 years). Mean follow-up was 12.4 months (5 to 28 months). There was no significant difference in Constant scores (p = 0.365) and no significant difference in Oxford scores (p = 0.686). There was 100% union in both groups. In the intramedullary group, there was one case of soft tissue irritation that settled after the pin was removed, one pin backed out and had to be revised with another pin. There were three superficial wound infections resulting in plate removal and 8 plates (53%) were removed.

Locked intramedullary fixation and plating are equally effective in the management of shortened displaced mid-shaft clavicle fractures.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 69 - 69
1 Jan 2011
Mason DJ Brakspear K Wilson C Williams R Kotwal RS
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Purpose: Since the neurotransmitter glutamate mediates nociceptive and pathological processes in arthritis, we have investigated how glutamate receptor and transporter expression varies with anatomical site or disease severity in subchondral bone of patients with osteoarthritis.

Methods and Results: Subchondral bone was sampled from tibial cuts derived from total knee arthroplasty (n=2, TKR, Kellgren Lawrence[KL] grade 3) and from tibial drill hole sites from high tibial osteotomy (n=2, HTO, KL grades 2 and 3) for osteoarthritis. RNA was extracted, reverse transcribed and RT-PCR performed for the housekeeping gene GAPDH, the glutamate transporter EAAT-1, and glutamate receptors (NR2A and KA1). Quantitative RT-PCR assessed differences in the expression of EAAT-1, a dominant negative splice variant called EAAT-1ex9skip and osteocalcin after normalisation to GAPDH.

Good quality RNA was obtained from bone cores removed from drill holes during HTO surgery, with GAPDH, EAAT-1, NR2A and KA1 expression detected. Osteocalcin expression was high indicating RNA was derived from osteoblasts and osteocytes, but did not vary with anatomical site or disease status. End-stage RT-PCR indicated differential expression of EAAT-1 between medial and lateral bone samples in total knee arthroplasty, however these differences were not significant by quantitative RT-PCR. In one patient, EAAT-1 expression was significantly reduced in the anterior zone versus the middle or posterior zones (ANOVA, p< 0.001). EAAT-1ex9skip represented a significant proportion of the total EAAT-1 mRNA expression in bone from TKR patients, but appeared less abundant in HTO samples.

Conclusion: We have shown for the first time that glutamate transporters and receptors are highly expressed in subchondral bone of patients with osteoarthritis and that EAAT-1 expression may vary with anatomical location and pathology. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate that occur in arthritis may contribute to pathological changes and nociception.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 411 - 411
1 Jul 2010
Mason DJ Brakspear K Wilson C Williams R Kotwal RS
Full Access

Purpose of the study: Since the neurotransmitter glutamate mediates nociceptive and pathological processes in arthritis, we have investigated how glutamate receptor and transporter expression varies with anatomical site or disease severity in subchondral bone of patients with osteoarthritis.

Methods and results: Subchondral bone was sampled from tibial cuts derived from total knee arthroplasty (n=2, TKR, Kellgren Lawrence grade 3) and from tibial drill hole sites from high tibial osteotomy (n=2, HTO, KL grades 2 and 3) for osteoarthritis. RNA was extracted, reverse transcribed and RT-PCR performed for the housekeeping gene GAPDH, the glutamate transporter EAAT-1, and glutamate receptors (NR2A and KA1). Quantitative RT-PCR assessed differences in the expression of EAAT-1, a dominant negative splice variant called EAAT-1ex9skip and osteocalcin after nor-malisation to GAPDH.

Good quality RNA was obtained from bone cores removed from drill holes during HTO surgery, with GAPDH, EAAT-1, NR2A and KA1 expression detected. Osteocalcin expression was high indicating RNA was derived from osteoblasts and osteocytes, but did not vary with anatomical site or disease status. End-stage RT-PCR indicated differential expression of EAAT-1 between medial and lateral bone samples in total knee arthroplasty, however these differences were not significant by quantitative RT-PCR. In one patient, EAAT-1 expression was significantly reduced in the anterior zone versus the middle or posterior zones (ANOVA, p< 0.001). EAAT-1ex9skip represented a significant proportion of the total EAAT-1 mRNA expression in bone from TKR patients, but appeared less abundant in HTO samples.

Conclusion: We have shown for the first time that glutamate transporters and receptors are highly expressed in subchondral bone of patients with osteoarthritis and that EAAT-1 expression may vary with anatomical location and pathology. Activation of these receptors and transporters by the increased synovial fluid concentrations of glutamate that occur in arthritis may contribute to pathological changes and nociception.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 411 - 411
1 Jul 2010
Kotwal RS Brakspear K Wilson C Williams R Mason DJ
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Purpose of the study: Since glutamate can activate both nociceptive and pathological processes, we have investigated glutamate signalling in patients with painful and asymptomatic meniscal tears to determine which components are expressed, whether this varies in different anatomical regions of the meniscus and whether it is influenced by pain or degeneration.

Methods and results: Meniscus samples were obtained from two patients undergoing arthroscopic partial meniscal resection for chronic degenerate painful meniscal tears, from one patient with a torn painless meniscus and from the less affected compartment of the knee joint of three patients undergoing total knee arthroplasty. Menisci were dissected into anatomical regions (anterior horn, body, posterior horn, inner vascular, outer avascular), cryosectioned and RNA extracted. RNA was reverse transcribed and PCR performed for the housekeeping gene GAPDH and glutamate receptor subunits (NR2A, AMPA GluR3, KA1). Absolute quantitative RT-PCR assessed mRNA expression of glutamate transporters (EAAT-1, EAAT-1ex9skip) and type I collagen after normalisation to GAPDH or total RNA.

Human meniscus expressed GAPDH, type 1 collagen, EAAT-1, EAAT-1ex9skip, NR2A, AMPA GluR3 and KA1 mRNAs. Levels of EAAT-1 expression, normalised to GAPDH, did not differ between the inner and outer halves, or in the anterior, middle or posterior regions of menisci from the less affected compartments of arthritic knees. EAAT-1 expression appeared greater in the 2 painful, compared with the single non-painful meniscus. Interestingly, EAAT-1ex9skip was significantly more common within the outer zones (ANOVA, P=0.040) and in the posterior horns of the menisci (ANOVA, p=0.038).

Conclusion: We have shown for the first time that glutamate receptors and transporters are expressed in human meniscus providing a potential mechanism underlying the pathophysiology of pain associated with a torn meniscus. Our preliminary data indicate that EAAT-1 and EAAT-1ex9skip expression may vary with extent of damage and anatomical location in the human meniscus.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 210 - 210
1 Mar 2010
Williams R
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Traditional management of spinal metastases has been for the most part palliative. In this decade however there has been a gradual shift towards extirpative treatment of spinal secondary malignancy in certain circumstances. The techniques of en bloc vertebral resection have gained more widespread acceptance improving the chances of successful wide or marginal resection of both primary and secondary tumours of the spine. Those metastatic lesions which are solitary and associated with a long period of latency from treatment of the primary lesion have a greater likelihood of improved survival with en bloc resection. Although technically demanding, these same techniques coupled with advances in spinal implantation may allow complete excision of extended primary malignancy of the spine previously considered unresectable. This presentation examines the indications for en bloc resection of secondary and extended primary malignancy of the spine. A case for early referral of solitary metastatic spinal lesions is presented in the hope of adding extirpative surgical techniques to the traditional armamentarium of theoncologist.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 437 - 437
1 Sep 2009
Lutton C Shiu R Crawford R Williams R Barker T Goss B
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Introduction: It is well known that the fate of biomaterials is determined by the distribution of proteins attached to the surface from the initial contact with blood or serum. This profile determines wether a material is inert, creates a foreign body response or is bioactive. Bioinert materials, such as polyethylene completely denature surface proteins, whilst materials inducing inflammatory responses are predisposed to complement protein attachment. Bioactive materials such autologous tissue grafts adsorb, but do not denature serum proteins such as fibronectin and Von Willebrand’s factor. This does not interfere with the healing cascade. This aim of this study is to prepare a synthetic bone graft substitute that activates the body’s autologous healing cascade by activating platelets, without activating a complement response through the controlled adsorption of serum proteins.

Methods: Polymers composed of varied concentration of acrylic acid (AA) and comonomers (methyl, ethyl and butyl methacrylates (MMA, EMA, BMA)) were prepared in glass vials by free radical polymerisation. Fresh blood was collected from a healthy donor and pipetted immediately into each chamber. Glass was used as a control. The chambers were incubated at 37o C for 2 hours. The surface morphology was examined using Scanning Electron Microscopy (SEM). Concentration of complement protein C5a and prothrombin fragments 1 and 2 were determined using commercial ELISA kits. Foreign body reaction (FBR) initiated by the biomaterial was estimated by counting leukocytes on clot sections using immunofluorescence.

Results: Extent of coagulation was correlated with plasma concentrations of Prothrombin fragments 1 and 2. These measurements show blood incubated with various polymers composed of different comonomers all promoted the formation of blood clots. It was found that the leukocyte population towards the interface of clot and polymer (AA:MMA) decreased with increasing surface acid concentration (65%AA:MMA 30 leukocytes/0.25mm2, glass 70 leukocytes/0.25mm2 (p< 0.05)). FBR is induced by the activation of complement system. The percentage of C5a concentration detected in blood incubated with various polymers composed of different comonomers relative to normal serum level of C5a (35ng/mL). No significant elevations of C5a were measured from polymer 65% AA:MMA and 65% AA:EMA. Glass induced vigorous complement response as expected. The synergistic combination of surface acid concentration and comonomers had a significant effect on extent of FBR. Increased acid concentration resulted in decreased C5a level with MMA and ET but increased level with BMA.

Discussion: The functional groups exposed on the surface of a material influence whether leukocyte or platelet activation is responsible for the subsequent physiological response. By modifying the combinations of surface acid concentrations and comonomers, we show that a biomaterial with an appropriate surface chemistry promotes the platelet plug formation and coagulation but down regulated foreign body reaction. This study shows that that a biomaterial with the appropriate surface chemistry to evoke the same coagulation response as damaged tissue, mediated through platelet activation and intrinsic and extrinsic coagulation, initiates the initial pathways of the bone healing cascade. This material is a realistic candidate for biomaterial induced bone regeneration.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 437 - 438
1 Sep 2009
Vasili C Lutton C Engman M Crawford R Williams R Goss B
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Introduction: The biological activity of autologous grafts is due to a number of proteins (growth factors) that control bone cell differentiation, proliferation and expression. Several of these have been isolated including; bone morphogenetic proteins 2 and 7. These are commercially available and regularly used with the intention of accelerating fracture healing, repairing critical sized defects and combating bone mineral loss. Whilst it is commonly recognised that multiple growth factors are present at differing times in the healing cascade, the usual delivery, both in the clinic and the laboratory, is of one growth factor delivered over a very short and early time period. Commonly growth factors are delivered in solution or from a collagen sponge and are quickly metabolised in the proteolytic wound healing environment. The physiological need for BMPs is later than the acute delivery at the time of surgery. The aim of this study is to develop a granular protein delivery system that enables controlled release of multiple proteins at a variety of time points.

Methods: A series of homogenous polymer granules 8mm3 were prepared by photo-polymerising 12uL of mixtures of methacrylated adipic acid anhydride (MAAA) and methyl methacrylate (MMA) or MAAA and butyl methacrylate (BMA) with molar ratios ranging from 100- 55 % (MSAA). Into each granule 5ug of a model drug, carmoisine was loaded and 1%w/w of 2,2-dimethoxy-2-phenyl-acetophenone (DMPA) photoinitiator was added per granule. The granules were exposed to UV light at 390nm for 14 minutes. Multilayered granules were prepared photo-polymerising 4uL layers of different monomer compositions in a similar method to the single layered method above. The composition of the multilayered granules was chosen to optimise the release profile. Carmoisine release profiles were determined by UV-visible spectroscopy.

Results: Homogenous granules composed of 100% MAAA released 90% of their payload by 24hrs, those composed of 90:10 MAAA:MMA released by 48hrs those composed of 70:30 MAAA:MMA released by 80hrs those composed of 60:40 MAAA:MMA released by 170hrs those composed of 70:30 MAAA: BMA released by 288hrs and those composed of 60:40 MAAA:BMA released by 456hrs. The multilayered granule had a sustained release of the model drug over the test period of 19 days.

Discussion: The limitation of most drug delivery systems, such as microspheres or collagen, is poor control over the release profile. The drug is ether released instantly or well after it is required. This multilayered composite drug delivery system enables the controlled release of different bioactive compounds at different time points between 0 and 19 days. By altering the drug loading in each layer we were able to sustain the release of one compound over this time period. This technology enables us to switch compounds at a given time points for example delivery of angiogenic factors for one week, proliferative factors for the second week and differentiation factors for the third week. This technology enables the pre-programmed release of multiple growth factors at times in the healing cascade when they meet the physiological need. A controlled release of growth factors at the appropriate time should improve bone healing rates.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 441 - 441
1 Sep 2009
Lutton C Shiu R Crawford R Williams R Goss B Barker T
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Introduction: Acute neurological damage from spinal cord injuries is believed to be localised, however it initiates a cascade of secondary events which usually leads to extensive and permanent neurological deficit. The secondary damage begins with the disruption of the blood-spinal cord barrier which unleashes a protracted inflammatory response. This prolonged inflammatory response is the catalyst for the secondary neurodegeneration and limited repair response that occurs in the chronic phase of a spinal cord injury. In this study it was proposed that the acute delivery of the angiogenic growth factors vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) would mediate inflammation and restore the blood spinal cord barrier. This would minimise the formation of glial scar and reduce the extent of secondary degeneration caudal and cranial to the lesion site.

Methods: Adult male Wistar rats (400g) were anesthetised. Complete laminectomies were performed at T10 and the animals were subjected to T10 hemisection. Animals were randomised to a treatment group (Lesion Control (LC), Gel Control (GC) and Angiogenic Gel (AG)) after the spinal cord was cut. Each treatment group had 6 animals sacrificed 3 months post injury. Sections were stained with antibodies to neurofilament 200, glial fibrillary acidic protein, smooth muscle actin (SMA), and fluorescent secondary antibodies and mounted with DAPI. The lesion size was measured from horizontal histological sections of the midline from 5 animals in each group using Axiovision version 4.6.1.0 (Carl Zeiss Imaging Solutions, Germany).

Results: The mean lesion size for the lesion control group was 2.09mm2, 1.97mm2 for the gel control group and 0.45mm2 for the active gel group. A t-test was used to confirm that the differences between the active gel and the two control groups were statistically significant (AG vs LC p= 0.021 AG vs GC p= 0.026). Histology showed a marked improvement of the morphology of the astrocytes in the treatment group over the control groups indicating that the treatment affected the population of reactive astrocytes. SMA staining showed an increased level of revascularisation in the treated lesions.

Discussion: Spinal cords do not heal because of prolonged inflammation which leads to secondary necrotic events, scar formation and the inhibition of regeneration. In this study we present a method for regulating the post lesion inflammatory signals, significantly reducing post-lesion scar formation. We propose the delivery of VEGF/PDGF significantly increases the permeability of the blood spinal cord barrier to neutrophils and macrophages and promotes angiogenesis observed in the lesion site. This may have two major effects on the progression of the spinal cord injury. Firstly, by increasing the initial influx of inflammatory cells it enables the faster removal of damaged tissue and phagocytosis of apoptotic cells thereby restoring the balance in favour of regulated inflammation and results in a finite and reduced inflammation time. Secondly, combination of VEGF and PDGF provides a robust angiogenic response and reduces ischemia, the population of reactive astrocytes and the capacity to form glial scars. These growth factors appear to moderate the secondary degenerative changes that result from the prolonged inflammation and thus promote the inherent capacity for regeneration.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 431 - 431
1 Sep 2009
Sugiyama S Wullschleger M Wilson K Vasili C Williams R Goss B
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Introduction: It has long been recognised that static plain x-rays are a sub-optimal method for the assessment of lumbar fusion. Blumenthal and Gil showed that radiographic assessment of fusion corresponded with operative findings only 69% of the time. Santos et al suggest that both plain x-rays and flexion/extension x-rays overestimate the fusion rate when compared to helical computed tomography (CT). To date there has been no correlation of CT assessment of fusion with surgical exploration. In this study we present an animal model of lumbar spine pseudarthrosis and compare three imaging modalities with micro-cut CT scanning and cadaveric assessment.

Methods: Approval was gained from the QUT animal ethics committee. Eleven mixed bred ewes were assigned to either a fusion group or an intentional pseudarthrosis (IP) group. A dorsal approach to the facet joints of L2/3 was made. The facet joints were destabilised by resecting the articulating surfaces with a rongeur. In the fusion group, the spinous processes of the destabilised segment were wired tightly together and a bone graft harvested from the iliac crest was placed into the joint space. In the IP group the bone graft bed was prepared similarly except that a small proportion of the articulating surface was left intact and a 1.0 cm2 roll of oxidised cellulose was placed into the facet joint space bilaterally. In the IP group the spinous processes were wired around an interspinous spacer which was later removed to create a similar degree of laxity in the fixation of each of the IP specimens. The animals were sacrificed at 6 months and static and dynamic lateral radiographs obtained. The spine was removed en bloc, and high speed fine cut (2mm) CT Scanning performed. The specimens were individually assessed for fusion by micro-cut CT scanning. Eight independent, blinded orthopaedic surgeons, were asked whether they considered the spine to be fused based on

plain x-ray

plain xray and flexion/extension x-rays and

plain x-ray and flexion/extension x-rays and CT scan.

These results were correlated with a fusion rate based on the micro CT. The specificity and sensitivity of these radiological measures in diagnosing pseudarthrosis and inter-rater reliability using Fleiss’ Kappa scores for each method were calculated.

Results: For assessing pseudarthrosis identified by microCT the plain film sensitivity was 0.41 and the specificity was 0.47. For assessing pseudarthrosis with plain and flexion extension xrays the sensitivity was 0.55 and the specificity was 0.33. For assessing pseudarthrosis with plain flexion extension xrays and CT the sensitivity was 0.81 and the specificity was 0.88. The Kappa score for plain films was 0.15, for flexion extension was 0.07 and CT was 0.54.

Discussion: This study suggests that plain radiographs and flexion extension radiographs are an unreliable measure of posterior lumbar fusion. The current clinical gold standard for assessment of fusion (CT) was able to correctly identify non-union in 80% of cases. Whilst no alternatives to structural assessment of the fusion mass with CT currently exist it is important to recognise the limitations of this technique.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 419 - 420
1 Sep 2009
Akhtar S Mofidi A Wilson C Williams R
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Purposes of the study: Anterior cruciate ligament (ACL) deficiency is associated with degenerative osteoarthritis especially when it is present with meniscal injury; We assessed the impact of certain aetiological factors in chondral degeneration in the ACL deficient knee.

Methodology and Results: Fifty-eight patients who underwent consecutive primary arthroscopic anterior cruciate ligament reconstruction using the four strand hamstring graft between 10/06/2004 and 29/06/2006 were retrospectively analysed.

Patient’s charts and radiology findings were reviewed with special attention to operative notes and preoperative knee MR imaging. Patients with knee symptoms prior to presenting injury were excluded.

The mechanism of injury, the time elapsed from the original injury to anterior cruciate ligament reconstruction, associated meniscal injury, and quality of cartilage in the knee- at the time of MR imaging and ACL reconstruction were noted. Degenerative cartilage changes were graded upon reconstruction using the Outerbridge classification.

The average time from Injury to MR imaging and MR to ACL reconstruction was 4.85 and 12.65 months respectively.

We found a direct relationship between the time elapsed after the ACL injury and the severity of the chondral lesion (p< 0.05). Furthermore, a significant worsening in chondral degeneration of the involved knee was seen when the MR imaging and ACL reconstruction were more than 12 months apart (p< 0.01).

Conclusion: We conclude that chondral lesions and degeneration are more likely to be caused by an extended period of knee instability following ACL injury as opposed to age related degeneration or direct trauma to the weight bearing area of the knee.

Early reconstruction may protect the knee from chondral wear and subsequent degenerative arthritis.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 12 - 12
1 Mar 2009
maripuri S Lewis D Evans R Dent C Williams R
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Introduction- Proximal humeral fractures remain a challenging problem. Most authors agree that anatomical reduction and stable fixation are essential to allow early range of motion. A variety of techniques have been described such as threaded pins, tension band wiring, screws, nails, plates and primary prosthesis. Locking plates score over other implants by the virtue of providing greater angular stability and better biomechanical properties. The Aim of the Study is to evaluate the functional outcome of PHILOS plate Osteosynthesis of displaced proximal humeral fractures.

Materials and Methods- A retrospective study of 50 patients treated with PHILOS plating for the 2 part, 3part and 4 part proximal humeral fractures with a minimum follow up of 1 year. All the patients were assessed in clinic by Constant Murley and ASES scoring systems. X-ray evaluation was done for fracture healing, AVN, mal-union, non-union, collapse of head, screw penetration and impingement of plate.

Results- Total of 50 acute displaced fractures of proximal humerus treated with PHILOS plating between 2003–2005 were assessed. Mean age was 64 years (15–86) Male to female ratio was 12:38, dominant to non-dominant ratio was 32:18. According to Neer’s classification 16 fractures were 2 part, 24 fractures were 3 part and 10fractures were 4 part. The overall mean Constant score was 73.4(range20–100) and ASES score was 71.7(range 25–98). Under 60 years of age the mean Constant and ASES scores were 83.5 and 83, over 60 years of age scores were 63.1 and 60.4 respectively. The complications include two deep infections which needed excision arthroplasty, one malunion, one subacromial impingement which needed plate removal after fracture healing. No mechanical failure, no non-union, no ANV was noted.

Conclusions- PHILOS plate Osteosynthesis is a reliable method of treating complex proximal humeral fractures. It provides good mechanical stability and allows rapid mobilization with out compromising fracture healing.