Reconstructive and regenerative traumatologic-orthopaedic surgery

S4 the same risks may not be as high with the use of an alternative bone morphogenetic protein, such as BMP-7, and if this substance is applied in an appropriate dose and in a contained form. Methods: Forty-eight patients underwent an anterior cervical fusion, with fully informed consent, over a 12 month period. These procedures were performed by a single surgeon, and ranged from 1 to 3 levels. All received an anterior interbody fusion using either PEEK, carbon fibre, or trabecular metal cages, with or without an anterior cervical plate. Forty patients had a combination of BMP-7 (one half to one unit; 1.75—3.5 mg BMP-7 and 0.5— 1.0 g collagen, the dose dependent upon the number of levels fused) and tricalcium phosphate placed within the cage; eight patients had tricalcium phosphate alone. No BMP-7 was placed outside the cage. Patients were evaluated prospectively for early adverse outcomes, including respiratory embarrassment, need for re-intubation, dysphagia requiring further investigation or treatment, re-operation, readmission, and mortality. Patients who underwent X-rays 24—72 h postoperatively had these films examined retrospectively by a blinded party. Prevertebral soft-tissue swelling at the level of the C6 vertebral body was compared between patients receiving BMP-7 and those not. This was also compared to a historical post-operative anterior cervical fusion cohort (who did not receive BMP-7) from the literature. Results: There were no early post-operative complications. Specifically, there were no instances of post-operative swelling, dysphagia, or respiratory impairment in patients receiving BMP-7, nor did any require surgical exploration or re-intubation. Prevertebral soft-tissue measurements at C6 24— 72 h post-operatively were carried out on 22 patients receiving BMP-7 and in 7 non-BMP patients. Mean prevertebral soft-tissue measurement in the BMP-7 group was 20.9 mm (16—27 mm). This compared with 18.7 mm (15—25 mm) in the non-BMP-7 group, and 18 mm in the historical control group. Conclusions: BMP-7 can be used safely in anterior cervical fusion surgery. A slight increase in postoperative prevertebral swelling in such patients is not clinically significant. The effect of BMP-7 on the rate and timing of fusion, as well as clinical outcome, is yet to be elucidated. DOI: 10.1016/j.injury.2006.08.008

Reconstructive and regenerative traumatologicorthopaedic surgery Platelet-derived factors and bone loss recovery M. Schiraldi a, G. Stennardo a, L. Mazzucco b, P. Borzini b

Abstracts a

Department of Orthopaedic and Traumatology, ‘‘Santi Antonio e Biagio’’ National Hospital, Alessandria, Italy b Department of Hematology and Blood Transfusion, ‘‘Santi Antonio e Biagio’’ National Hospital, Alessandria, Italy Background: Both recombinant and wild-type platelet-derived growth factors have been demonstrated to enhance soft and bony tissue healing. Experimental animal trials and human experiences have largely demonstrated that platelet-derived factors induce short-time bone-tissue regeneration, while longterm effects including morphogenetics and bone remodelling remain questionable. Frequently, orthopaedic and trauma surgery has to do with bony-tissue defects needing reconstruction. In this case platelet-derived growth factor seems to be recommended to hasten recovery time. Methods: Platelet gel was produced from the patient’s own blood. Platelets were recovered from blood centrifugation. Platelet Rich-Plasma (PRP) (platelet count 1—2  109/L) was obtained from further centrifugation. PRP gelification was induced through addition of Ca++ and autologous recalcified plasma. When reconstructing bone defects, platelet gel was mixed to cancellous bone allograft or to demineralised bone matrix and stabilised with plates, i.m.-nails depending of the anatomical site and type of non union or introduced with a trocar in the delay union fractures. After reconstruction, radiographs were taken at intervals of 4—8—12 weeks and evaluated the callus formation. Between March 2004 and February 2005 we used plateletderived growth factors in 48 patients; in 20 cases with high energy delayed union fractures (at least after 3 months), in 16 cases with delayed union after open fractures (Gustilo II—III) and in 12 cases with non union (avascular/atrophic type) fractures. The patients age ranged 21—81 years (mean age 49) and the ratio men/woman was 3:1. We compared each group with a control group treated 1 year previously. The minimum follow-up was 1 year. Results: Ninety percent of recovery was achieved in the high energy delayed union fracture group, 78% in the delayed union open fracture and 83% of recovery in the non union group compared to 78% and 69% and 74%, respectively, in the control group. The time of recovery was reduced by 28% in high energy fracture, by 14% in the high energy open fracture and by 23% in the non union group compared with the control group. Conclusions: Platelet-derived-factors delivered as a platelet-gel mixed to allogeneic bone allograft or to demineralised bone matrix is suitable to fasten the clinical outcome of patient submitted to recon-

Abstracts structive traumatologic-orthopaedic surgery. Bone regeneration seems to occur more quickly using the autologous platelet gel as a surgical ancillary product. No adverse reaction attributed to the platelet gel was observed. DOI: 10.1016/j.injury.2006.08.009

The role of combined pharmaceutical therapies with OP-1 in the treatment of fractures and delayed unions David G. Little Orthopaedic Research and Biotechnology, The Children’s Hospital at Westmead, Sydney, Australia OP-1 (BMP-7 in collagen carrier) is one of the most potent anabolic agents for bone repair. We hypothesised that as BMPs also stimulate bone resorption (catabolism), the combination of OP-1 with a potent bisphosphonate could result in increased amount and strength of bone produced. Research has thus far focused on the optimal timing/duration of bisphosphonate therapy to increase net bone production whilst minimising any negative impacts on remodelling. OP-1 50 mg was placed in a critical defect in the rat femur. Zoledronic acid (ZA) was given as a single dose either at surgery or delayed by 2 weeks. Callus volume increased over OP-1 alone by 45% and 86% in the OP-1 ZA and OP-1 ZA 2W groups, respectively ( p < 0.01). The increased callus volume in the OP-1 ZA 2W group translated to increases in strength of 107% and stiffness of 148% ( p < 0.05). BFR was not significantly different between OP-1 groups regardless of ZA treatment, indicating similar anabolic effects. In a further experiment, OP-1 dose was reduced to 25 mg, 10 mg and 5 mg. Similar results we achieved with 10 mg OP-1 combined with ZA as were seen with 25 mg of OP-1 alone. Next, in a model of open fractures, 35% of saline treated femoral fractures in the rat went on to nonunion. PTH treatment at 50 mg/(kg day) or 10 mg/ (kg day) had no effect on increasing union rates in this open fracture model. OP-1 alone led to union in 95% of cases. OP-1 followed by ZA led to union in 100% of cases, with an increase of 49% in load to failure over OP-1 alone. ZA alone without an anabolic agent did not increase union rate in this study. We have applied this combination to the treatment of congenital pseudarthrosis of the tibia in children who have NF-1. Despite a published study by Lee et al. showing only one of five patients united when treated with OP-1 alone, we have achieved

S5 union in four cases thus far using combination therapy of OP-1 followed by ZA. These studies indicate that anabolic therapy with OP-1 and a well-timed dose of anti-catabolic treatment can increase callus volume and strength and lead to early, robust union in difficult circumstances. DOI: 10.1016/j.injury.2006.08.010

Experimental and clinical experience with OP-1W for bone and meniscus repair Francisco Forriol Research Unit Hospital FREMAP, Department of Trauma & Orthopaedics, Hospital FREMAP, CrtaPozuelo 61, 28220 Majadahonda (Madrid), Spain Objective: OP-11 is a bone morphogenetic protein with many potential clinical applications. We study it experimentally in bone defects and in meniscus repair. Five clinical cases are presented. Material and methods: To analyse the repair of a bone defect in sheep mandible using allograft of frozen rib, OP-11, Platelet-Rich Plasma (PRP) and combination of frozen rib allograft with OP-11. We resected 6 cm mandible defect in 15 sheep, 8 years old. The animals were sacrificed 2 months after the operation. To study the effect of OP-11 (BMP-7) on the repair of the avascular area of the meniscus two orifices 4 mm in diameter were made in the anterior half of the meniscus in 24 4-month-old sheep. Animals were allowed to develop for 6, 12 and 25 weeks. Results and conclusion: In the control and PRP groups no images of bone formation were observed. The OP-11 group showed bone formation and the group that combined the frozen rib allograft with OP-11 was that which filled the gap best through endochondral and also fibrous ossification. Putty1 remained in place for the first 6 weeks, then was reabsorbed and disappeared, while in all the specimens with OP-1 Putty1 (BMP-7), significant penetration of the cells was observed from the superficial meniscus into the interior of the orifices, accompanied by fibrous tissue, from the 12 week onwards. DOI: 10.1016/j.injury.2006.08.011

Tissucol-based scaffold in the treatment of knee cartilage defects: Experimental resurfacing by embryonic stems cells P.L. Tranquilli Leali, A. Manunta, D. Zarelli, F. Zirattu Orthopaedic Department, University of Sassari, Italy