BONE REGENERATION OF A CRITICAL-SIZED DEFECT IN SHEEP WITH A 3D PRINTED SCAFFOLD COATED WITH A BIOMETIC FILM CONTAINING LOW-DOSE OF BMP-2

Jun 29, 2022, 1:40 PM
10m
Room: S2

Room: S2

Speaker

Schoffit, Sarah (Ecole Nationale Vétérinaire d’Alfort (Université Paris-Est), 7 avenue du général de Gaulle, 94704 Maisons-Alfort Cedex, France and Laboratoire de Biologie, Bioingénierie et Bioimagerie Ostéeo-Articulaire (B3OA—UMR CNRS 7052) Université Paris Diderot, 10 A )

Description

"Introduction: Large bone defects are a challenge for orthopedic surgeons. BMPs are the most potent bone inductors and accelerators of bone growth. However, poor BMP-2 retention by scaffolds leads to its rapid clearance from implantation sites,1 and thus, require the use of supra-physiological doses. Serious concerns regarding BMP-2-related adverse effects have been reported (including osteolysis, ectopic bone formation, and inflammatory response)2, and prompt the need for new carrier materials for optimizing BMPs spatiotemporal delivery. Our study aimed to evaluate the regeneration of a critical-sized segmental bone defect in a sheep preclinical model, with a 3D architectured poly L-lactic acid (PLLA) scaffold coated with a biomimetic film containing BMP-2. The osteoinductive properties of these films deposited on different types of implantable materials have previously been demonstrated both in vitro3,4 and in vivo.5–7

Methodology: PLLA cylindrical scaffolds (25mm high, 14mm in diameter and with cubic pores of ~880µm) were 3D printed, coated with a biomimetic film previously developed by members of our team8,9 and subsequently loaded with BMP-2. A 25mm-long mid-diaphyseal segmental metatarsal bone defect was created and stabilized with a plate in 9 sheep. Defects were filled with either (i) PLLA scaffold loaded with (from 300 to 600 µg) BMP-2 (n=7) or (ii) BMP-2-free PLLA scaffold (n=2). Monthly radiographic follow-up was performed until animal sacrifice at 4 months. The newly-formed bone between the defect edges and within the scaffold was quantified in explanted specimens with micro-CT. Specimens were then processed for undecalcified histology to characterize bone formation/resorption, bone-scaffold interface, inflammatory response and vascularization of tissue.

Results: Consistent radiographic bone union was observed in 7/7 animals when BMP-2 containing film-coated PLLA scaffolds were implanted, whereas none of the 2 animals implanted with the BMP-2-free PLLA scaffold did achieve bone union. Neither abnormal bone resorption nor chronic inflammatory response were observed with the bioactive scaffold containing BMP-2. Dense newly-formed bone filled with numerous osteocytes was observed all around and in direct contact with the scaffold material pillars.

Conclusions: 3D printed PLLA scaffolds coated with a biomimetic films containing BMP-2 provided consistent radiographic bone union in a preclinical critical-size segmental defect without noticeable deleterious effects. This strategy opens new avenues for the replacement of segmental bone defects.

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  8. Bouyer, M. et al., Biomaterials. 104, 168–181 (2016)
  9. Bouyer, M. et al., Mater. Today Bio 11, 100–113 (2021)"

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