Reconstruction of Large-scale Defects with a Novel Hybrid Scaffold Made from Poly(L-lactic acid)/Nanohydroxyapatite/Alendronate-loaded Chitosan Microsphere: in vitro and in vivo Studies.
A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.
Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
Hongwei
H
Wu
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410011, China.|Department of Orthopedics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States.
Pengfei
P
Lei
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Gengyan
G
Liu
Biomaterials Innovation Research Centre, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, 02115, USA.
Yu
Y
Shrike Zhang
Biomaterials Innovation Research Centre, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, 02115, USA.
Jingzhou
J
Yang
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410011, China.|Department of Neurosurgery, School of Medicine, Yale University, New Haven, Connecticut, USA.
Longbo
L
Zhang
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410011, China.
Jie
J
Xie
Department of Orthopedics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States.|Department of Orthopedics, VA Boston Healthcare System, Boston, MA, USA.
Wanting
W
Niu
Biomaterials Innovation Research Centre, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, 02115, USA.|Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Hua
H
Liu
Powder Metallurgy Research Institute, Central South University, Changsha, 410083, Hunan, China.
Jianming
J
Ruan
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410011, China. csuhuyihe@163.com.
Yihe
Y
Hu
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, 410013, China. zcy1958@medmail.com.cn.
Chaoyue
C
Zhang
D019386:Alendronate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000737:chemistry*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite / Q000737:chemistry; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
D018786:Bone Substitutes; D019344:Lactic Acid; D048271:Chitosan; D017886:Durapatite; D019386:Alendronate