Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo

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.

Calcium Supplement by Tetracycline guided amorphous Calcium Carbonate potentiates Osteoblast promotion for Synergetic Osteoporosis Therapy

“…In Figure 7 A, the femur BMD was distinctly different between the SHAM group and the OVX group, with a value of 0.186±0.007 g/cm 2 in the SHAM group and 0.118±0.002 g/cm 2 in the OVX group. The BMD of the OVX group was reduced by 36.56% compared to that in the SHAM group, indicating that the osteoporotic model rats were established successfully 37 .…”

An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection

“…The composited nanoparticle was constituted from osteoconductive calcium phosphate, anti-bactericidal TiO 2 and magnetic Fe 3 O 4 . As widely used bone substitutes, calcium phosphates could act as a natural reservoir for calcium and phosphate ions to conducive new bone regeneration 25 . While TiO 2 has great success in orthopedics and dentistry due to its benign biocompatibility, chemical stability, mechanical properties, and excellent photocatalytic capacity to release reactive oxygen species (ROS).…”

Resveratrol benefits the lineage commitment of bone marrow mesenchymal stem cells into osteoblasts via miR‐320c by targeting Runx2

“…Due to their pronounced differentiation potentials, BMSCs have been widely used in clinical therapies, especially in bone regeneration and tissue engineering (Li, Xin, et al., 2019). Besides, the osteogenic potential of BMSCs exhibits a vital role in the balance of bone environment (Tang et al., 2019). For example, transplantation of BMSCs could be used as a novel method for wound healing, helping to overcome the current limitations to stem cell therapy and solve the present problems of stem cell therapy in the field of wound regeneration, such as limited abilities of differentiation into the desirable cell types in wounds (Shou et al., 2018).…”