Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo

Abstract

The macro-pore sizes of porous scaffold play a key role for regulating ectopic osteogenesis and angiogenesis but many researches ignored the influence of interconnection between macro-pores with different sizes. In order to accurately reveal the relationship between ectopic osteogenesis and macro-pore sizes in dorsal muscle and abdominal cavities of dogs, hydroxyapatite (HA) scaffolds with three different macro-pore sizes of 500–650, 750–900 and 1100–1250 µm were prepared via sugar spheres-leaching process, which also had similar interconnecting structure determined by keeping the d/s ratio of interconnecting window diameter to macro-pore size constant. The permeability test showed that the seepage flow of fluid through the porous scaffolds increased with the increase of macro-pore sizes. The cell growth in three scaffolds was not affected by the macro-pore sizes. The in vivo ectopic implantation results indicated that the macro-pore sizes of HA scaffolds with the similar interconnecting structure have impact not only the speed of osteogenesis and angiogenesis but also the space distribution of newly formed bone. The scaffold with macro-pore sizes of 750–900 µm exhibited much faster angiogenesis and osteogenesis, and much more uniformly distribution of new bone than those with other macro-pore sizes. This work illustrates the importance of a suitable macro-pore sizes in HA scaffolds with the similar interconnecting structure which provides the environment for ectopic osteogenesis and angiogenesis.

Biphasic calcium phosphate with submicron surface topography in an Ovine model of instrumented posterolateral spinal fusion

“…Indeed, during preclinical in vivo studies, grafts with optimized physicochemical properties have presented better outcomes than those with suboptimal properties. For instance, calcium phosphate phase composition, macro‐porosity (ie, macro‐pore size and interconnectivity) and bioactivity have been directly related to the in vivo tissue response, neovascularization and bone‐forming potential in ectopic and orthotopic sites . Moreover, presence of a submicron surface topography and micro‐porosity has been linked to substantially enhanced bone‐inducing properties of calcium phosphates …”

“…For instance, calcium phosphate phase composition, [38][39][40][41][42][43] macroporosity [44][45][46][47][48][49][50] (ie, macro-pore size and interconnectivity) and bioactivity 51 have been directly related to the in vivo tissue response, neovascularization and bone-forming potential in ectopic and orthotopic sites. [40][41][42][43] Moreover, presence of a submicron surface topography and micro-porosity has been linked to substantially enhanced boneinducing properties of calcium phosphates.…”

Effect of pore size in bone regeneration using polydopamine‐laced hydroxyapatite collagen calcium silicate scaffolds fabricated by 3D mould printing technology

“…According to the studies performed by Karageorgiou and Kaplan, scaffolds with pore sizes >300 μm are recommended for repairing large bone defect as they resulted in enhanced new bone and capillary formations. Among various types of scaffolds, excellent osteoinductions have been shown in the ones with pore sizes within the range of 500‐1200 μm . It was also demonstrated that ceramic scaffold with 300‐500 μm pores is optimal for osteogenesis; the ones with 300 μm pores, which exhibited inferior bone ingrowth .…”

“…Among various types of scaffolds, excellent osteoinductions have been shown in the ones with pore sizes within the range of 500-1200 μm. 5,6 It was also demonstrated that ceramic scaffold with 300-500 μm pores is optimal for osteogenesis; the ones with 300 μm pores, which exhibited inferior bone ingrowth. 7 Regarding vascularization for the optimal pore size, Chang et al 8 reported that large pores in β-tricalcium phosphate scaffold were beneficial for the blood vessel ingrowth, and the pores smaller than 400 μm limit the growth of blood vessels.…”

Synergistic Effects on Incorporation of β-Tricalcium Phosphate and Graphene Oxide Nanoparticles to Silk Fibroin/Soy Protein Isolate Scaffolds for Bone Tissue Engineering

“…It is generally accepted that the pore geometry in a scaffold, including pore size, pore shape, porosity, and pore interconnecting pattern, plays an important role in cell adhesion, proliferation, and migration as well as tissue ingrowth [38,39]. Lager pore sizes favor tissue ingrowth and vascularization, resulting in better osteogenesis, while smaller pores lead to osteochondral ossification [40]. An ideal bone scaffold should have 100-600 µm pore size with 60-80% porosity to provide enough space for cell migration, tissue ingrowth, and vascularization.…”