Additively manufactured biphasic construct loaded with BMP-2 for vertical bone regeneration: A pilot study in rabbit

Abstract

Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the site of dental implant placement. In this proof of concept study, we investigated the potential of a biphasic polycaprolactone construct combined with a hyaluronic acid based hydrogel loaded with recombinant human bone morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The biphasic scaffold consisted of an outer shell manufactured by fused deposition modelling, mimicking native cortical bone and providing mechanical and space maintenance properties essential for bone formation. Within this shell, a 90% porous melt electrospun microfibrous mesh mimicking the architecture of cancellous bone was incorporated in order to facilitate hydrogel loading and subsequent osteogenesis and angiogenesis. The in vitro performances of the biphasic construct demonstrated that BMP-2 was released in a sustained manner over several weeks and that cell viability was maintained in the hydrogel over 21 days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin, osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2. In vivo assessment of the biphasic scaffold was performed using a dose of 30 μg of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology and micro-CT analysis of the elevated space demonstrated that the hydrogel and the presence of BMP-2 enabled bone formation. However, this was limited to the immediate vicinity of the calvarial bone. The amount of newly formed bone was relatively small which was likely due to poor vascularisation of the extraskeletal space. The utilisation of this biomimetic biphasic construct with excellent space maintenance properties can be of interest in dentistry although the in vivo model requires refinement to demonstrated appropriate efficacy.

Effect of Bone Morphogenic Protein-2-Loaded Mesoporous Strontium Substitution Calcium Silicate/Recycled Fish Gelatin 3D Cell-Laden Scaffold for Bone Tissue Engineering

“…Those growth factors are therefore thought to initiate, stimulate and increase the normal bone formation cascade. Recombinant human BMP-2 (rhBMP-2) is already available in the USA for various orthopedic uses such as tibial fractures [39]. However, current treatments using rhBMP-2 are currently rather limited as we are unable to directly inject rhBMP-2 into bone defects.…”

Biomimetic Aspects of Oral and Dentofacial Regeneration

“…The outer wall of the biphasic material simulated cortical bone, while the core simulated medullary bone. BMP was released in a sustained manner from the construct, while it provided mechanical and space maintenance properties through the cortical part and osteogenesis and angiogenesis through the medullary [219]. Gene delivery is also a lucrative method as it ensures prolonged and stable production of the protein, reviewed by Park et al for BMP2 in dentistry [220].…”

Ten Years of Micro-CT in Dentistry and Maxillofacial Surgery: A Literature Overview

“…The use of animal models seems to be a required step in testing new bone regeneration materials [96]. The in vivo applicability of bioengineered 3D constructs [97] and bone graft substitutes is usually evaluated in animals models as rats, rabbits, mini pigs bone defects, and applications are recorded in dentistry [98][99][100][101][102] as in MFS [103][104][105]. Mainly, the biomaterials and bone grafts investigated for tissue engineering applications are:…”

“…The in vitro applicability of bone graft substitutes is usually evaluated on extracted teeth in dentistry as in the studies conducted on polylactic acid (PLA)-based mineral-doped scaffolds [110] and in MFS [105]. Turco et al performed a comparison of the biological, chemical, and structural features of four different commercially available bone substitutes derived from an animal or a synthetic source, analyzing the biomaterials structures by micro-CT [111].…”