Evaluation of osteogenesis and angiogenesis of icariin loaded on micro/nano hybrid structured hydroxyapatite granules as a local drug delivery system for femoral defect repair

Abstract

Icariin has been identified to promote osteogenic differentiation of bone mesenchymal stem cells (BMSCs). However, whether icariin could enhance angiogenic factor expression of BMSCs, which may be vital for bone repair, needs to be explored. Moreover, how to construct a delivery system of icariin and its repair capability in bone defects are still unknown. In the present study, the effects of icariin on the osteogenic differentiation and angiogenic factor expression of BMSCs were firstly evaluated.Moreover, new micro/nano hybrid structured HAp (micro/nano HAp) granules were fabricated to construct the delivery system of icariin, and the osteogenesis and angiogenesis of icariin loaded on micro/nano HAp granules in a rat femoral plug defect model were evaluated by micro-CT measurements, sequential fluorescent labeling and the histological assay. The in vitro results showed that icariin significantly improved osteogenic differentiation of rat BMSCs demonstrated by the enhanced alkaline phosphatase (ALP) activity and gene expression of runt-related transcription factor-2 (Runx2), ALP, collagen type I (Col I), osteocalcin (OCN) and OCN protein secretion. Moreover, icariin induced the angiogenic genes expression of BMSCs, such as vascular endothelial growth factor (VEGF) and angiotensin 1 (ANG1). Furthermore, the activation of the AKT signaling pathway was observed in BMSCs upon treatment with icariin, and these enhancement effects could be blocked by LY294002, which suggested that the AKT signaling pathway was involved in the osteogenic differentiation and angiogenic factor expression of BMSCs induced by icariin.More importantly, micro/nano HAp granules with rod-like shapes were successfully fabricated and acted as delivery carriers for icariin. Consequently, icariin loaded on micro/nano HAp granules could promote new bone formation and blood vessel formation. These results demonstrated that icariin could enhance osteogenic differentiation and angiogenic factor expression of BMSCs via the AKT signaling pathway, moreover, the novel micro/nano HAp granules could act as carriers for icariin to repair bone defects via enhancing osteogenesis and angiogenesis.

The role of antimiR-26a-5p/biphasic calcium phosphate in repairing rat femoral defects

“…These results validated earlier studies that reported that BCP is the ideal choice of scaffolds for tissue-engineered bone (12,13,15). HA, with a calcium to phosphorus ratio (Ca/P) of 1.67, is considered to be the stable phase and is hardly absorbed, which may be an obstacle for its use in bone regeneration (42,43). By contrast, β-TCP, with a Ca/P ratio of 1.5, was easily absorbed (43).…”

Extraction and Characterization of Novel Natural Hydroxyapatite Bioceramic by Thermal Decomposition of Waste Ostrich Bone

“…Different researchers have used various biogenic resources for the extraction of HAp. Barakat et al [18] and Sofronia et al [19] used bovine bones, Lu et al [20] used pig bone and teeth, and Abdulrahman et al [21], Wu et al [5], and Khandelwal and Prakash [1] used wastes from eggshells. Similarly, Ferreira et al [22] extracted from ostrich eggshells.…”

“…It is a calcium/phosphate-based bioceramic which is chemically like the inorganic constituent of the bone matrix (a very complex bone tissue) with the general formula Ca 10 (PO 4 ) 6 (OH) 2 [ 4 ]. This ceramic is not only biocompatible, osteoconductive, noninflammatory, and nonimmunogenic but also bioactive; i.e., it has an ability to form a direct bond with living tissues and promote tissue growth [ 5 ]. Owing to these properties and chemical likeness to the mineral constituent of the bone matrix, it is a prime filler material to replace damaged bone or is a coating on implants to promote bone ingrowths into prosthetic implants and many more non-load bearing applications [ 6 ].…”

RNA-Seq investigation and in vivo study the effect of strontium ranelate on ovariectomized rat via the involvement of ROCK1

“…In recent years, more and more attention has been focused on the HAp with nanostructures surfaces because it can increase specific surface area and surface energy of the material and the structure of pore space itself can promote cell viability, migration and differentiation [17]. In addition to above advantage, nano-HAp particulates also showed the function of adsorbing and releasing drugs along with osteogenic and angiogenic effects through loaded icariin [18] and quercetin [19], etc. However, the local application of SrR in animal models of osteoporosis and new nano-HAp particulates loaded SrR has not yet been explored.…”