RESUMEN
Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation (p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population.
RESUMEN
BACKGROUND: This is a Phase IV, national, multicentre, retrospective study to observe the real-world use of rhBMP-2 in France. HYPOTHESIS: There was no statistical hypothesis, the statistical analyses were descriptive in nature. PATIENTS AND METHODS: Data was collected from patient medical files in 10 French spinal centres. Primary objectives were to understand which patients were treated with rhBMP-2, commercialised in Europe as InductOs™ and how rhBMP-2 was used during spinal fusion surgery in France between 2011 and 2012. RESULTS: Four hundred patients (634 levels) treated with rhBMP-2 were included in the analysis. The most frequent primary diagnostic indication for rhBMP-2 use was degenerative disc disease (DDD; 129/400; 32.3% of patients) followed by spondylolisthesis (119/400; 29.8%), deformity (59/400; 14.8%) and pseudoarthrosis (29/400; 7.3%). The most frequently treated level was L4-L5 (33.8% of levels in 53.5% of patients); followed by L5-S1 (29.8%, 47.3%), L3-L4 (16.7%, 26.5%), and L2-L3 (7.3%, 11.5%), all other levels (less than 5% of patients). No interbody fusion device was used in 42.7% of levels. Wetted matrix of rhBMP-2 was placed in the interbody space in 58.4% of levels (370/634). The most common procedure for rhBMP-2 treatment was posterior lumbar fusion (PLF) (221/634; 34.9% of levels), followed by anterior lumbar interbody fusion (ALIF) (188/634; 29.7%), posterior lumbar interbody fusion (PLIF) (111/634; 17.5%), lateral lumbar interbody fusion (LLIF) (106/634; 16.7%), transforaminal lumbar interbody fusion (TLIF) (4/634; 0.6%) and 'other' (4/634; 0.6%). Thirty-one adverse events of Interest (AEI) were recorded in 27 patients. One AEI was considered related to rhBMP-2. Unplanned secondary spine interventions at index level treated with rhBMP-2 were required in 4 patients. DISCUSSION: In years 2011 and 2012 when the surgeries captured in this retrospective study were done, rhBMP-2 was indicated for single level (L4-S1) anterior lumbar spine fusion as a substitute for autogenous bone graft in adults with DDD. The most common procedure for the treatment with rhBMP-2 was PLF (off-label use), followed by ALIF (on-label use). The safety findings confirm a predictable and manageable safety profile. LEVEL OF EVIDENCE: IV.