Abstract
The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine.
Highlights
The treatment of large bone defects resulting from trauma, non-union, tumor resections or craniofacial malformations remains challenging
The PLGA tubes were coated with a polyelectrolyte multilayer film (PEM) film made of 24 alternating layers of PLL and hyaluronic acid (HA)
The films were post-loaded with bone morphogenetic protein (BMP)-2 [31] at various concentrations ranging from 5 to 100 μg/mL In this previous study, we already proved that there is an interaction between HA and BMP-2 at pH 3 and pH 7.4 [31], which contribute to explain the observed high affinity of BMP-2 for the PEM films
Summary
The treatment of large bone defects resulting from trauma, non-union, tumor resections or craniofacial malformations remains challenging. [1] These conventional grafts, which combine osteogenic cells and osteoinductive and osteoconductive properties, [2, 3] are limited by donor-site morbidity, chronic inflammation or the risk of disease transmission Synthetic bone scaffolds, such as osteoconductive ceramics [2] and biodegradable synthetic polymers, [4] have been developed to mimic bones, but they lack osteoinductive signals. The poor retention of BMP-2 by collagen leads to its rapid clearance from implantation sites, [9] and supra-physiological doses (at least a few mg) are required. These issues have recently raised serious concerns regarding ectopic bone formation, pain and cancer risk. These issues have recently raised serious concerns regarding ectopic bone formation, pain and cancer risk. [10] there is a clear need to optimize the spatiotemporal delivery of BMPs using new carrier materials. [11]
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