title: Development of Injectable Citrate-Based Bioadhesive Bone Implants.
abstract: Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2-4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF.
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China ; Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
authors.forename: Denghui
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Mehdizadeh
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Tran
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Ruisong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Biology, College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Dadi
authors.initials: D
authors.lastname: Jin
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China ; Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang