Frédéric Sailhan

Secondary Structure of rhBMP-2 in a Protective Biopolymeric Carrier Material

Efficient delivery of growth factors is one of the great challenges of tissue engineering. Polyelectrolyte multilayer films (PEM) made of biopolymers have recently emerged as an interesting carrier for delivering recombinant human bone morphogenetic protein 2 (rhBMP-2 noted here BMP-2) to cells in a matrix-bound manner. We recently showed that PEM made of poly(l-lysine) and hyaluronan (PLL/HA) can retain high and tunable quantities of BMP-2 and can deliver it to cells to induce their differentiation in osteoblasts. Here, we investigate quantitatively by Fourier transform infrared spectroscopy (FTIR) the secondary structure of BMP-2 in solution as well as trapped in a biopolymeric thin film. We reveal that the major structural elements of BMP-2 in solution are intramolecular β-sheets and unordered structures as well as α-helices. Furthermore, we studied the secondary structure of rhBMP-2 trapped in hydrated films and in dry films since drying is an important step for future applications of these bioactive films onto orthopedic biomaterials. We demonstrate that the structural elements were preserved when BMP-2 was trapped in the biopolymeric film in hydrated conditions and, to a lesser extent, in dry state. Importantly, its bioactivity was maintained after drying of the film. Our results appear highly promising for future applications of these films as coatings of biomedical materials, to deliver bioactive proteins while preserving their bioactivity upon storage in dry state.

Bone morphogenetic protein and orthopaedic surgery: Can we legitimate its off-label use?

PurposeBone morphogenetic proteins (BMP) are recombinant osteoinductive proteins with their primary role being to promote bone formation. The off-label use of BMP in orthopaedic surgery has dramatically increased. However, reports of complications with BMP have emerged, and the safety of these proteins in orthopaedics is questioned. The purpose of this review was to evaluate safe situations in which BMP should be used and situations in which their use should be restricted.MethodWe recorded all studies from PubMed database from 2002 (date of first authorisation for both BMPs) until January 2014 using “BMP” or “bone morphogenetic protein”. Then we screened and extracted all studies dealing with orthopaedic surgery. All situations in which BMP were used, even cases reports, were considered, and complications reported were then listed.ResultsSituations in which it seems safe and efficient to use BMP are long-bone nonunions, or arthrodesis as an alternative or combined to autograft in small-bone loss. Surgeons and patients should be aware of transient aseptic wound swelling when BMP is located superficially. The use of BMP in spine surgery for intersomatic fusion is efficient but should be restricted to approaches that respect the vertebral canal to avoid neurological complications.ConclusionThis review is an off-label map of BMP use in orthopaedics during the past 10 years. Our results could provide a useful tool to help decisions around when to use a BMP in a specific complex, and sometimes off-label, situation.

Low-dose BMP-2 and MSC dual delivery onto coral scaffold for critical-size bone defect regeneration in sheep

Tissue‐engineered constructs (TECs) combining resorbable calcium‐based scaffolds and mesenchymal stem cells (MSCs) have the capability to regenerate large bone defects. Inconsistent results have, however, been observed, with a lack of osteoinductivity as a possible cause of failure. This study aimed to evaluate the impact of the addition of low‐dose bone morphogenetic protein‐2 (BMP‐2) to MSC‐coral‐TECs on the healing of clinically relevant segmental bone defects in sheep. Coral granules were either seeded with autologous MSCs (bone marrow‐derived) or loaded with BMP‐2. A 25‐mm‐long metatarsal bone defect was created and stabilized with a plate in 18 sheep. Defects were filled with one of the following TECs: (i) BMP (n = 5); (ii) MSC (n = 7); or (iii) MSC‐BMP (n = 6). Radiographic follow‐up was performed until animal sacrifice at 4 months. Bone formation and scaffold resorption were assessed by micro‐CT and histological analysis. Bone union with nearly complete scaffold resorption was observed in 1/5, 2/7, and 3/6 animals, when BMP‐, MSC‐, and MSC‐BMP‐TECs were implanted, respectively. The amount of newly formed bone was not statistically different between groups: 1074 mm3 [970–2478 mm3], 1155 mm3 [970–2595 mm3], and 2343 mm3 [931–3276 mm3] for BMP‐, MSC‐, and MSC‐BMP‐TECs, respectively. Increased scaffold resorption rate using BMP‐TECs was the only potential side effect observed. In conclusion, although the dual delivery of MSCs and BMP‐2 onto a coral scaffold further increased bone formation and bone union when compared to single treatment, results were non‐significant. Only 50% of the defects healed, demonstrating the need for further refinement of this strategy before clinical use.

Retrospective multicenter study by the French Spine Society of surgical treatment for spinal metastasis in France

INTRODUCTION The occurrence of spinal metastasis is a turning point in the progression of cancer. The optimal management has not been well defined. The aim of this study was to identify the various treatments currently being used in France and to determine the benefits of surgical treatment. MATERIAL AND METHODS The records of patients treated between 2011 and 2015 at seven spine surgery centers in France were reviewed retrospectively. The pain level (VAS), McAfee scale, walking ability and Frankel Grade were evaluated at inclusion and at 6-months postoperative. The Tomita and Tokuhashi prognostic scores were also determined. RESULTS The cohort consisted of 319 patients. Preoperatively, 63.5% of patients could walk without assistance and 66% were Frankel Grade E. Twenty percent of patients were bed-ridden according to the Karnofsky Performance Status. According to the Tokuhashi criteria, 44% were predicted to have less than 6 months to live. The Tomita score recommended palliative surgery in 48% of cases. Potentially unstable lesions were present in 67% of patients. The surgical indication was made because of a neurological deficit in 40% of cases, to alleviate pain in 30% of cases, and for an instability in 30% of cases. Spinal cord decompression and posterior fixation were the most common procedures. The overall complication rate was 38.6%. At 6-months postoperative, 24 patients had died of the 245 available for review. Only 13 patients could not walk (5.3%), 69.4% of patients were Frankel Grade E and pain levels were significantly lower that preoperatively (2.4 vs. 4.6, p<0.001). DISCUSSION This studys findings are evidence of the difficulties encountered when treating spinal metastases. The main prognostic scores do not appear to be valid for these patients. A large number of patients were operated urgently because of a neurological deficit, before the treatment could be discussed in a multidisciplinary team (MDT) meeting. Nevertheless, the surgical treatment of these patients is associated with an acceptable complication rate and clinical improvement. CONCLUSION Surgical treatment of spinal metastases is not well standardized; thus many different strategies are used. There is evidence that it improves the quality of life in most patients by reducing their pain and allowing them to walk again. However, this treatment must be discussed in the context of an MDT meeting before it is carried out. These patients should be evaluated early on by a spine surgeon to reduce the need for emergency surgery when a neurological deficit appears.