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.

Enhanced osteogenesis of hydroxyapatite scaffolds by coating with BMP-2-loaded short polylactide nanofiber: a new drug loading method for porous scaffolds

Porous hydroxyapatite(HA)is widely used in porous forms to assist bone defect healing.However,further improvements in biological functions are desired for meeting complex clinical situations such as impaired bone regeneration in poor bone stock.The extracellular matrix(ECM)of human tissues is characterized by nanofibrous structures and a variety of signal molecules.Emulating these characteristics are expected to create a favorable microenvironment for cells and simultaneously allow release of osteogenic molecules.In this study,short polylactide fibers containing BMP-2 were prepared by electrospinning and coated on porous HA scaffolds.The coating did not affect porosity or pore interconnectivity of the scaffold but improved its compressive strength markedly.This fiber coating produced burst BMP-2 release in 1 day followed by a linear release for 24 days.The coating had a significantly lower rat calvarial osteoblasts(RCOBs)adhesion(vs.uncoated scaffold)but allowed normal proliferation subsequently.Bone marrow stem cells(MSCs)on the coated scaffolds expressed a significantly increased alkaline phosphatase activity relative to the uncoated ones.After implantation in canine dorsal muscles,the coated scaffolds formed significantly more new bone at Weeks 4 and 12,and more blood vessels at Week 12.This method offers a new option for drug delivery systems.

Preparation of multigradient hydroxyapatite scaffolds and evaluation of their osteoinduction properties

Porous hydroxyapatite(HA)scaffolds are often used as bone repair materials,owing to their good biocompatibility,osteoconductivity and low cost.Vascularization and osteoinductivity of porous HA scaffolds were limited in clinical application,and these disadvantages were need to be improved urgently.We used water-in-oil gelation and pore former methods to prepare HA spheres and a porous cylindrical HA container,respectively.The prepared HA spheres were filled in container to assemble into composite scaffold.By adjusting the solid content of the slurry(solid mixture of chitin sol and HA powder)and the sintering temperature,the porosity and crystallinity of the HA spheres could be significantly improved;and mineralization of the HA spheres significantly improved the biological activity of the composite scaffold.The multigradient(porosity,crystallinity and mineralization)scaffold(HA-700)filled with the mineralized HA spheres exhibited a lower compressive strength;however,in vivo results showed that their vascularization ability were higher than those of other groups,and their osteogenic Gini index(Go:an index of bone mass,and inversely proportional to bone mass)showed a continuous decrease with the implantation time.This study provides a new method to improve porous HA scaffolds and meet the demands of bone tissue engineering applications.