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
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.
Purpose The objective of this study was to determine the effectiveness of collagenated biphasic calcium phosphate (CBCP) as a carrier for bone morphogenetic protein-2 (BMP-2) at the early stage of healing in rabbit sinus. Material and Methods In 16 rabbits, BMP-2-loaded CBCP was grafted into one sinus (the BMP group) and saline-soaked CBCP was grafted into another sinus (the CTL group). The groups were assigned randomly. After 2 weeks (n = 8) or 4 weeks (n = 8), radiographic and histological ana...
Last. Jung-Bo Huh(PNU: Pusan National University)H-Index: 22
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The aim of this study was to improve osteoblast function by delivering two growth factors, PDGF-BB and BMP-2, incorporated onto heparinized titanium (Hep-Ti) substrate. To achieve co-delivery of PDGF-BB and BMP-2, the surface of anodized Ti was immobilized with heparin, and then the two growth factors were coated onto the Hep-Ti surface. Incorporation of the two growth factors onto Hep-Ti was evaluated by SEM and XPS. Incorporated PDGF-BB and BMP-2 were released from the Hep-Ti substrate in a su...
Last. Xinquan Jiang(SJTU: Shanghai Jiao Tong University)H-Index: 53
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Objectives Icariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown. Materials and methods Effects of icariin on cell proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize underlying mechanisms, its effects o...
Bone vasculature plays a vital role in bone development, remodeling and homeostasis. New blood vessel formation is crucial during both primary bone development as well as fracture repair in adults. Both bone repair and bone remodeling involve the activation and complex interaction between angiogenic and osteogenic pathways. Interestingly studies have demonstrated that angiogenesis precedes the onset of osteogenesis. Indeed reduced or inadequate blood flow has been linked to impaired fracture hea...
#2Kaili Lin(CAS: Chinese Academy of Sciences)H-Index: 52
Last. Zhiyuan Zhang(SJTU: Shanghai Jiao Tong University)H-Index: 51
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Abstract Tissue engineering strategies to construct vascularized bone grafts potentially revolutionize the treatment of massive bone loss. The surface topography of the grafts plays critical roles on bone regeneration, while adipose derived stem cells (ASCs) are known for their capability to promote osteogenesis and angiogenesis when applied to bone defects. In the present study, the effects of hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod, and micro-nano-hybrid (the hybrid o...
Last. Junying Miao(SDU: Shandong University)H-Index: 3
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The surface characteristics of biomaterials, especially regarding the sustained delivery of bone morphogenetic protein-2 (BMP-2), can possibly provide a novel and effective drug delivery system that can enhance osteogenesis. In this study, we evaluated the BMP-2 adsorption and release ability of the surface biomimetic hydroxyapatite (HAp) nanostructure on a new HAp-coated genipin-chitosan conjugation scaffold (HGCCS), and the resulting osteogenic differentiation of rat bone marrow-derived mesenc...
Last. Ke-Ming Chen(Capella Education Company)H-Index: 15
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article Icariin, a prenylated flavonol glycoside isolated from Epimedii herba, has been found to be a potent stimulator of osteogenic differentiation and has potential application inpreventing bone loss. However, the signaling pathway underlying itsosteogeniceffect remainsunclear.Wehypothesizedthattheosteogenic activity of icariin isrelated to the nitric oxide (NO) signal pathway and PI3K/AKT pathway in its upstream. Rat bone marrow stromal cells (rBMSCs) were cultured in osteogenic medium and t...
Last. Ralf H. Adams(WWU: University of Münster)H-Index: 83
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Bone homeostasis and repair declines with ageing and the mechanisms regulating the relationship between bone growth and blood vessel formation have remained unknown; this mouse study identifies the endothelial cells that promote the formation of new bone, a small microvessel subtype that can be identified by high CD31 and high Emcn expression.
New nanocomposite membranes with high bioactivity were fabricated using the electrospinning. These nanocomposites combine a degradable polymer poly(l/dl)-lactide and bone cell signaling carbonate nano-hydroxyapatite (n-HAp). Chemical and physical characterization of the membranes using scanning electron microscopy, Fourier transform infrared spectroscopy and the wide angle X-ray diffraction evidenced that nanoparticles were successfully incorporated into the fibers and membrane structure. The in...
Icariin, the main active flavonoid glucoside isolated from Herba epimedii (HEF), is an anabolic agent in bone that has been reported to prevent bone loss in ovariectomized rats and postmenopausal women. However, the molecular mechanism for this anabolic action of Icariin remain largely unknown. Here, we found that Icariin could promote MC3T3-E1 osteoblastic cell proliferation and reduce cell apoptosis, associated with increased mRNA levels of positive regulators of cell cycle gene Cyclin E and p...
Last. Shaohua Ge(SDU: Shandong University)H-Index: 21
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Abstract Bone repair is a complex and multifactorial regulatory process, and achieving precise and efficient bone regeneration is a fundamental goal of bone tissue engineering. Promoting the synergistic effects of cell recruitment, immunomodulation, angiogenesis, and osteogenesis is a feasible strategy to augment bone repair. In this work, the multifunctional agent stromal cell-derived factor-1 (SDF-1) was loaded onto hydroxyapatite (HAp) nanowires and observed to endow HAp/polylactic acid (PLA)...
Abstract The regeneration of bone defects in osteoporotic patients presents a big challenge. Icariin (Ica), which is the main active component of traditional Chinese medicine - herba epimedii, has been widely loaded to scaffolds for the treatment of bone fracture and osteoporosis. To increase drug loading capacity, and meanwhile achieve a stable and safe drug delivery, in present study, a novel icariin derivative - thiolated icariin (Ica-SH) molecule with good cytocompatibility and bioactivity w...
Tissue engineering has been an inveterate area in the field of regenerative medicine for several decades. However, there remains limitations to engineer and regenerate tissues. Targeted therapies using cell-encapsulated hydrogels, such as mesenchymal stem cells (MSCs), are capable of reducing inflammation and increasing the regenerative potential in several tissues. In addition, the use of MSC-derived nano-scale secretions (i.e., exosomes) has been promising. Exosomes originate from the multives...
Last. Marivalda M. Pereira(UFMG: Universidade Federal de Minas Gerais)H-Index: 27
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Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process,...
A novel natural hydroxyapatite (HAp) bioceramic was extracted from the ostrich cortical bone by the thermal decomposition method. HAp was characterized by different analytical tools such as thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). Removal of organic impurities from the bone powder was confirmed by TGA analysis. FTIR spectra of HAp confirmed the presence of the major functional group...
#1Saeid Kargozar(MUMS: Mashhad University of Medical Sciences)H-Index: 26
#2Francesco Baino(Polytechnic University of Turin)H-Index: 42
Last. Masoud Mozafari(IUMS: Iran University of Medical Sciences)H-Index: 52
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Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart attack, stroke, wound healing). Many pharmaceutical companies have expended huge efforts on both stimulation and inhibition of angiogenesis. During the last decade, the nanotechnology revolution has made a great impact in medicine, and regulatory approvals are starting to be achieved for nanomedicines to treat a wide range of dise...
Last. Steve Guofang Shen(SJTU: Shanghai Jiao Tong University)H-Index: 19
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Bone implants play a crucial role in bone repairing. Nevertheless, low capability of osteoinductivity and osteogenic differentiation for bone regeneration are disadvantages of bone implants. Therefore, it is imperative to develop a general and facile technology to promote the bioactivity of existing implants. Herein, a facile amorphous carbon-coating approach was developed to stimulate osteogenesis on diverse biomaterials, including bioceramics, biometals, and biopolymers via magnetron sputterin...
Last. Maryam Rezaei(UT: University of Tehran)H-Index: 5
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Hydroxyapatite (HA) is a member of the calcium phosphates family (Table 1) and like the other ones is known as a bioceramic with specific advantages raise from chemical similarity to the mammalian inorganic structure. In comparison to other CaPs, HA has highest thermodynamic stability and solubility (after Fluorapatite) in physiological conditions.
Last. Ming Li(Kunming Medical University)H-Index: 1
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This study aimed to identify the osteogenesis effect of icariside II (ICSII) and icaritin (ICT) in vitro. Bone marrow mesenchymal stem cells (BMSCs) were treated with ICSII and ICT in order to detect the proliferation and differentiation of BMSCs, the expression of the osteogenesis-related proteins with or without osteogenic medium (OM) and genes, Runt-related transcription factor 2 (Runx-2), osteocalcin (OCN), osteopontin (OPN), osterix, and basic fibroblast growth factor (bFGF), and the phosph...
Both the topographic surface and chemical composition modification can enhance rapid osteogenic differentiation and bone formation. Till now, the synergetic effects of topography and chemistry cues guiding biological responses have been rarely reported. Herein, the ordered micro-patterned topography and classically essential trace element of strontium (Sr) ion doping were selected to imitate topography and chemistry cues, respectively. The ordered micro-patterned topography on Sr ion-doped bioce...