Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of commercially available particulated biomaterials dedicated to intra-oral bone regeneration applications. The purpose of this study was to evaluate the in vitro and in vivo biocompatibility and osteoinductive properties of two calcium-phosphate (CaP)-based scaffolds manufactured by SLA three-dimensional (3D) printing. Pellets and macro-porous scaffolds were manufactured in pure hydroxyapatite (HA) and in biphasic CaP (HA:60-TCP:40). Physico-chemical characterization was performed using micro X-ray fluorescence, scanning electron microscopy (SEM), optical interferometry, and microtomography (μCT) analyses. Osteoblast-like MG-63 cells were used to evaluate the biocompatibility of the pellets in vitro with MTS assay and the cell morphology and growth characterized by SEM and DAPI-actin staining showed similar early behavior. For in vivo biocompatibility, newly formed bone and biodegradability of the experimental scaffolds were evaluated in a subperiosteal cranial rat model using μCT and descriptive histology. The histological analysis has not indicated evidences of inflammation but highlighted close contacts between newly formed bone and the experimental biomaterials revealing an excellent scaffold osseointegration. This study emphasizes the relevance of SLA 3D printing of CaP-based biomaterials for intra-oral bone regeneration even if manufacturing accuracy has to be improved and further experiments using biomimetic scaffolds should be conducted. K E Y W O R D Sbone regeneration, bone scaffold, histology, microtomography, stereolithography

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3D printing technologies are a promising approach to treat intra-oral bone defects, especially those with poor regenerative potential. However, there is a lack of evidence regarding the impact of internal design specifications on the bone regenerative potential. Here, an in silico approach to optimize the internal design of calcium phosphate-based scaffolds for bone regeneration is proposed. Based on an in silico model of neotissue formation, a gyroid 3D-printed scaffold is designed and manufactured using UV stereolithography of bioceramic materials. An orthogonal lattice structure 3D-printed scaffold and a particulate xenograft are used as control groups. The scaffolds are implanted subperiosteally under a shell on rat calvarium for 4 or 8 weeks and bone neoformation performances are investigated by nanofocus computed tomography and decalcified histology. After 8 weeks, the gyroid group is associated with a higher ingrowth potential of the bone and is characterized by signs of osteoinduction (newly formed bone islands). The bone to material contact is similar between the gyroid and the particulate groups. The present results reinforce this in silico modeling strategy to design calcium phosphate-based 3D scaffolds and the gyroid experimental internal architecture seems to be highly promising for intra-oral bone regeneration applications.

Large bone defects are a challenge for orthopedic surgery. Natural (bone grafts) and synthetic biomaterials have been proposed but several problems arise such as biomechanical resistance or viral/bacterial safety. The use of metallic foams could be a solution to improve mechanical resistance and promote osseointegration of large porous metal devices. Titanium cylinders have been prepared by additive manufacturing (3D printing/rapid prototyping) with a geometric or trabecular microarchitecture. They were implanted in the femoral condyles of aged ewes; the animals were left in stabling for 90 and 270 days. A double calcein labeling was done before sacrifice; bones were analyzed by histomorphometry. Neither bone volume, bone/titanium interface nor mineralization rate were influenced by the cylinder’s microarchitecture; the morphometric parameters did not significantly increase over time. Bone anchoring occurred on the margins of the cylinders and some trabeculae extended in the core of the cylinders but the amount of bone inside the cylinders remained low. The rigid titanium cylinders preserved bone cells from strains in the core of the cylinders. Additive manufacturing is an interesting tool to prepare 3D metallic scaffolds, but microarchitecture does not seem as crucial as expected and anchoring seems limited to the first millimeters of the graft.

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