Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo
Authors: Zhenzhong Zhu
Liyan Shen
XingFang Yu
Qian Tang
Huazi Xu
Changqing Zhang
Zhichao Hu
Haixiao Liu
Haiming Jin
Gang Wu
Gang Zheng
Journal: Theranostics (2019)
Discipline: CLINICAL MEDICINE
Keywords: calcitriol; critical-size bone defect; layer-by-layer assembly; osteoporosis; polysaccharide.
Affiliations: Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi road, 325027 Wenzhou, China., The second School of Medicine, Wenzhou Medical University, 109, Xueyuanxi road, 325027 Wenzhou, China., Department of Orthopaedic Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China., Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Vrije University Amsterdam and University of Amsterdam, Amsterdam, Nord-Holland, the Netherlands.

Abstract:  Incorporating a biomimetic coating and integrating osteoinductive biomolecules into basic bone substitutes are two common strategies to improve osteogenic capabilities in bone tissue engineering. Currently, the underlying mechanism of osteoporosis (OP)-related deficiency of osteogenesis remains unclear, and few treatments target at OP-related bone regeneration. Herein, we describe a self-assembling polyelectrolyte multilayered (PEM) film coating with local immobilisation of calcitriol (Cal) in biphasic calcium phosphate (BCP) scaffolds to promote osteoporotic bone regeneration by targeting the calcium sensing receptor (CaSR). Methods: The ovariectomy-induced functional changes in bone marrow mesenchymal stem cells (BMSCs), protective effects of Cal, and the potential mechanism were all verified. A PEM film composed of hyaluronic acid (HA) and chitosan (Chi) was prepared through layer-by-layer self-assembly. The morphology, growth behaviour, and drug retention capability of the composite scaffolds were characterised, and their biocompatibility and therapeutic efficacy for bone regeneration were systematically explored in vitro and in vivo.Results: The osteogenic differentiation, adhesion, and proliferation abilities of ovariectomised rat BMSCs (OVX-rBMSCs) decreased, in accordance with the deficiency of CaSR. Cal effectively activated osteogenesis in these OVX-rBMSCs by binding specifically to the active pocket of the CaSR structure, while the biomimetic PEM coating augmented OVX-rBMSCs proliferation and adhesion due to its porous surface structure. The PEM-coated scaffolds showed advantages in Cal loading and retention, especially at lower drug concentrations. HA/Chi PEM synergised with Cal to improve the proliferation, adhesion, and osteogenesis of OVX-rBMSCs and promote bone regeneration and BCP degradation in the critical-size calvarial bone defect model of OVX rats. Conclusion: A composite scaffold based on BCP, created by simply combining a biomimetic PEM coating and Cal immobilisation, could be clinically useful and has marked advantages as a targeted, off-the-shelf, cell-free treatment option for osteoporotic bone regeneration. 

Retracted: No

PubPeer comments:
 Two images in Figure 7B appear to overlap. *** ![file] , 
 April 20, 2021  The authors regret that the image of BCP group without Cal in 12 W in the Fig. u200bFig.7B7B was wrongly attached due to their carelessness in integrating figures. The correct version is shown below. This image substitution would not affect any results presented in the originally-published version, nor the corresponding text description and the conclusion of the paper. The authors apologize for any inconvenience or misunderstanding that this error may have caused. ![file] ,