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

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 mm 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 mm exhibited much faster angiogenesis and osteogenesis,and much more uniformly distribution of new bone than those with othermacro-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.

Au,Pd and maghemite nanofunctionalized hydroxyapatite scaffolds for bone regeneration

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering(BTE)allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation.In this study,Mg-HA-Coll type I scaffolds(Mg-HA-based scaffolds)were nanofunctionalized with gold nanorods(Au NRs),palladium nanoparticles(Pd NPs)and maghemite nanoparticles(MAG NPs).Nanofunctionalized Mg-HA-based scaffolds(NF-HA-Ss)were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells(hADSCs).Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control(Mg-HA-based scaffold),whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%,respectively.Similar evidences were found for the osteoinductive properties showing relevant calcium deposits(25% higher than the control)for MAG nanofunctionalization,while a decreasing of cell differentiation(20% lower than the control)for both Au NRs and Pd NPs derivatization.These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs.The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs.These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

Bi-/multi-modal pore formation of PLGA/hydroxyapatite composite scaffolds by heterogeneous nucleation in supercritical CO_2 foaming

Scaffolds with multimodal pore structure are essential to cells differentiation and proliferation in bone tissue engineering. Bi-/multi-modal porous PLGA/hydroxyapatite composite scaffolds were prepared by supercritical C02 foaming in which hydroxyapatite acted as heterogeneous nucleation agent. Bimodal porous scaffolds were prepared under certain conditions, i.e. hydroxyapatite addition of 5%, depressurization rate of 0.3 MPa. min-1, soaking temperature of 55 ℃, and pressure of 9 MPa. And scaffolds presented specific structure of small pores （122 μM ± 66 μm） in the cellular walls of large pores （552 μm ±127 μm）. Furthermore, multimodal porous PLGA scaffolds with micro-pores （37 μM ± 11μM） were obtained at low soaking pressure of 7.5 MPa. The interconnected porosity of scaffolds ranged from （52.53 ± 2.69）% to （83.08±2.42）% by adjusting depressurization rate, while compression modulus satisfied the requirement of bone tissue engineering. Solvent-free CO2 foaming method is promising to fabricate bi-/multi-modal porous scaffolds in one step, and bioactive particles for osteogenesis could serve as nucleation agents.