title: Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect.
abstract: Insulin is considered to be a classical central regulator of energy homeostasis. Recently, the effect of insulin on bone has gained a lot of attention, but little attention has been paid to the application in bone tissue engineering. In this study, porous nanohydroxyapatite/collagen (nHAC) scaffolds incorporating poly lactic-co-glycolic acid (PLGA) particles were successfully developed as an insulin delivery platform for bone regeneration. Bioactive insulin was successfully released from the PLGA particles within the scaffold, and the size of the particles as well as the release kinetics of the insulin could be efficiently controlled through Shirasu porous glass premix membrane emulsification technology. It was indicated that the nHAC/PLGA composite scaffolds possessed favorable mechanical and structural properties for cell adhesion and proliferation, as well as the differentiation into osteoblasts. It was also demonstrated that the nHAC/PLGA scaffolds implanted into a rabbit critical-size mandible defect possessed tissue compatibility and higher bone restoration capacity compared with the defects that were filled with or without nHAC scaffolds. Furthermore, the in vivo results showed that the nHAC/PLGA scaffolds which incorporated insulin-loaded microspheres with a size of 1.61 μm significantly accelerated bone healing compared with two other composite scaffolds. Our study indicated that the local insulin released at the optimal time could substantially and reproducibly improve bone repair.
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.|Hospital of Stomatology, Shanxi Medical University , Taiyuan, 030001, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Helin
authors.initials: H
authors.lastname: Xing
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: E
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing, 100190, China.
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing, 100190, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing, 100190, China.
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Stomatology, Chinese PLA General Hospital , Beijing 100853, China.
authors.forename: Hongchen
authors.identifier: http://orcid.org/0000-0001-7524-4796
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D003094:Collagen; D006018:Glycols; D007328:Insulin; D019344:Lactic Acid; D049329:Nanostructures; D011100:Polyglycolic Acid; D016062:Porosity; D011817:Rabbits; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D006018:Glycols; D007328:Insulin; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: PLGA; bone tissue engineering; composite scaffold; drug delivery system; hydroxyapatite; insulin