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Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 49 - 49
1 Nov 2016
Sermer C Kandel R Hurtig M Anderson J Theodoropoulos J
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Osteoarthritis (OA) is a debilitating disease characterised by degradation of articular cartilage and subchondral bone remodeling. Current therapies for early or midstage disease do not regenerate articular cartilage, or fail to integrate the repair tissue with host tissue, and therefore there is great interest in developing biological approaches to cartilage repair. We have shown previously that platelet-rich plasma (PRP) can enhance cartilage tissue formation. PRP is obtained from a patient's own blood, and is an autologous source of many growth factors and other molecules which may aid in healing. This raised the question as to whether PRP could enhance cartilage integration. We hypothesise that PRP will enhance integration of bioengineered cartilage with native cartilage.

Chondrocytes were isolated from bovine metacarpal-phalangeal joints, seeded on a porous bone substitute (calcium polyphosphate) and grown in the presence of FBS to form an in vitro model of osteochondral-like tissue. After 7 days, the biphasic constructs were soaked in PRP for 30 minutes prior to implantation into the core of a ring-shaped biphasic explant of native bovine cartilage and bone. Controls were not soaked in PRP. The resulting implant-explant construct was cultured in a stirring bioreactor in serum free conditions for 2 weeks. The integration zone was visualised histologically. A push-out test was performed to assess the strength of integration. Matrix accumulation at the zone of integration was assessed biochemically and the gene expression of the cells in this region was assessed by RT-PCR. Significance (p<0.05) was assessed by a student's t-test or one-way ANOVA with tukey's post hoc.

PRP soaked bioengineered implants, integrated with the host tissue in 73% of samples, whereas control bioengineered implants only integrated in 19% of samples based on macroscopic evaluation (p<0.05). The integration strength, as determined by the normalised maximum force to failure, was significantly increased in the PRP soaked implant group compared to controls (219 +/− 35.4 kPa and 72.0 +/− 28.5 kPa, respectively, p<0.05). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP treated implant group, compared to untreated controls after 2 weeks (p<0.05). Immunohistochemical studies revealed that the integration zone was rich in collagen type II and aggrecan. The cells at the zone of integration in the PRP soaked group had a 2.5 fold increase in aggrecan gene expression (p=0.05) and a 3.5 fold increase in matrix metalloproteinase 13 expression (p<0.05) compared to controls.

PRP soaked bio-engineered cartilage implants showed improved integration with native cartilage compared to non-treated implants, perhaps due to the increased matrix accumulation and remodeling at the interface. Further evaluation is required to determine if PRP improves integration in vivo.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1475 - 1479
1 Oct 2010
Gortzak Y Kandel R Deheshi B Werier J Turcotte RE Ferguson PC Wunder JS

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H2O2) and 50% zinc chloride (ZnCI2) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions.

Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H2O2 and 50% ZnCI2. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures.

These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 3 - 3
1 Mar 2005
Gerrand C Wunder J Kandel R O’Sullivan B Catton C Bell R Griffin A Davis A
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Aim: To explore the relationship between anatomical location in lower extremity soft tissue sarcoma and function as measured by the Musculoskeletal Tumour Society (MSTS 93) rating and Toronto Extremity Salvage Score (TESS).

Methods: 207 patients of median age 54 years (15 to 89) were reviewed. 58 tumours were superficial and 149 deep. Deep tumours were allocated to one of 9 locations based on anatomical compartments.

Results: Treatment of superficial tumours did not lead to significant changes in MSTS (mean 90.6% vs 93.0%, p=0.566) or TESS (mean 86.4% vs 90.9%, p=0.059). Treatment of deep tumours lead to significant reductions in MSTS and TESS (mean 86.9% vs. 83.0%, p=0.001. mean 83.0% vs. 79.4%, p=0.015). There were no significant differences in MSTS and TESS when overall scores were compared by anatomical location. Exploratory analysis of MSTS subscales showed groin tumours were more painful than others, and posterior calf tumours had the lowest scores for gait. TESS subscales analysis suggested groin and buttock tumours were associated with difficulty sitting, and groin tumours were associated with difficulty dressing. Further exploratory analysis suggested “conservative” surgical excision of low-grade liposarcomas in all locations was associated with a significant decrease in functional scores.

Conclusion: There is significant variation in MSTS and TESS subscale scores when anatomical locations are compared. The “conservative” surgery used in the treatment of low-grade fatty tumours in all locations has a significant impact on functional scores.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 485 - 486
1 Apr 2004
Davis A O’Sullivan B Bell R Turcotte R Catton C Wunder J Chabot P Hammond A Benk V Isler M Freeman C Goddard K Bezjak A Kandel R Sadura A Day A James K Tu D Pater J Zee B
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Introduction Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing pre-operative versus post-operative RT is described.

Methods One hundred and ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, six weeks, and three, six, 12, and 24 months after surgery. One hundred and eighty-five patients had function data.

Results Patients treated with post-operative RT had better function with higher MSTS (25.8 v 21.3, P < .01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at six weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health sub-scales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first two years after treatment.

Conclusions The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.