Speaker
Description
"Introduction:
Highly porous biodegradable scaffolds made of polycaprolactone (PCL) and ceramic designed as three-dimensional (3D) guiding structures with rectilinear filling to facilitate bone regeneration have successfully been translated from preclinical studies into clinics as part of a scaffold-guided bone tissue engineering (SGBTE) concept. However, advances in 3D printer technology now allow the fabrication of novel scaffold structures, such as those with Voronoi design, which are potentially better able to mimic natural bone properties than those printed with rectilinear infill. The 3D Voronoi tessellation is based on random discrete seed points used to create cells that form a highly porous network structure with high mechanical strength. To pave the way for successful implementation, further developments of the SGBTE concept, such as the use of novel Voronoi scaffold design, are based on the principles of rigorous in vitro and preclinical in vivo testing to evaluate biocompatibility, biomechanical stability and tissue integration capacity.
Methodology:
Tubular composite medical-grade PCL hydroxyapatite (HA; wt% 96:4) scaffolds (outer diameter 10 mm, inner diameter 4 mm, height 15 mm) with 3D Voronoi tessellation were 3D-printed using additive manufacturing (BellaSeno GmbH, Germany). Scaffold porosity was assessed using micro-CT scanning (μCT 50, Scanco Medical AG, Switzerland). To determine the Young’s modulus, unconfined, uniaxial compression tests (2 kN load cell) were performed under simulated physiological conditions of 1% phosphate-buffered saline (PBS) solution (37°C) with strain rate of 0.1 mm/s (30 kN Instron 5567, Melbourne, Australia). In vitro hydrolytic degradation was assessed over time by performing scanning electron microscopy (SEM), mass loss, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC) at time points of 0 (baseline), 30, 60, 90, 120, 150, and 180 days. During the 180 days PCL-HA scaffolds were immersed in sterile 1% PBS (10 ml) in closed 15 ml tubes, to avoid evaporation, and maintained in incubator at 37°C. At each time point, samples were washed three times with deionized water and incubated in vacuum overnight at 37°C before assessment. Biocompatibility of subcutaneously implanted scaffolds loaded with freshly harvested sheep bone graft materials was assessed using an an ectopic bone formation model of athymic nude rats. Assessment methods for in vitro and in vivo characterization included histology, immunohistochemistry, SEM and histomorphometry.
Results:
Scaffold µCT assessment revealed high mean porosity of 72.8% (± 0.94) (n=8). Further, the Youngs modulus of scaffolds (n=5) was 11.4 MPa (± 1.1). The PCL-HA scaffolds (n=7) exhibited slow degradation behaviour over the 180-day assessment period as observed with SEM, mass loss calculations, and molecular weight changes as determined by GPC and crystallinity with DSC. Immunohistochemistry, Goldner's trichrome staining and SEM analysis of specimens (n=8) collected from rats (n=2) eight weeks after implantation show integrative physiological response at the interface between scaffold and different types of bone graft without signs of inflammatory reaction.
Conclusion:
High porosity and favourable biomechanical properties, along with slow and predictable degradation was observed. Histological examination showed good biocompatibility with no adverse host tissue reactions, making PCL-HA scaffolds with Voronoi design a suitable candidate for use in SGBTE."
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