Osteoporosis New drugs Review
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Osteoporosis New drugs Review
Denosumab is a breakthrough fully human monoclonal antibody approved by both the FDA and EMA in 2010. It had been fast tracked by FDA for treatment and prevention of postmenopausal osteoporosis, treatment and prevention of bone loss in hormone treated prostate and breast cancer patients. The FDA advisory committee (August 13, 2009) to review the safety and efficacy had recommend approval for treatment of high risk bone loss postmenopausal osteoporosis in women and hormone ablation treated men with prostate cancer, with black box warnings for serious side effects and under REMS program. Denosumab may have peak sales in the range of $5 billion within 5 years after approval in US, Europe, Japan and other major markets. New additional indications may follow and it may cross sales of $1 billion in 2012 due to unmet medical need from patients and healthcare providers. Clinical data published and in public domain indicates a superior safety and efficacy profile. FDA has asked for modifications and details of the REMS for treatment of osteoporosis. Denosumab (Prolia, Amgen) after FDA Review was approved under REMS on 1 June 2010. For prevention of osteoporosis and cancer indications, FDA has asked for new studies to show that there was no incidence of increased cancer. Amgen has submitted the BLA for prevention of bone loss in cancer patients on 14 June 2010. FDA had granted it the priority review status and approved the use for reducing fractures and other bone problems in cancer patients on 18 November, 2010. The European Committee for Human Medicinal Products CHMP recommended its approval in December 2009. It was approved by the EMA on 28 may 2010 and was launched there in the 3Q2010. Data presented at the ASCO and ESMO 2010 meetings has been added. The UK cost control agency NICE has recommended the clinical use of Prolia in osteoporosis. Data presented at EULAR showed increased bone density in women taking denosumab for 6 years and significantly reduced risk of fractures in elderly patients. The drug is approved in Switzerland for the prevention of bone loss in breast and prostate cancer patients undergoing hormone therapy besides osteoporosis. Sales of the drug were $33 million in 2010 and peak potential sales of over $ 5 billion per year.
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Denosumab (Prolia, Amgen) FDA Review & Approval - Krishan Maggon

Denosumab (Prolia, Amgen) FDA Review & Approval - Krishan Maggon | Osteoporosis New drugs Review | Scoop.it
Denosumab is a breakthrough fully human monoclonal antibody approved by both the FDA and EMA in 2010. It had been fast...
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Home : Bone biology and disease

Home : Bone biology and disease | Osteoporosis New drugs Review | Scoop.it
Bone biology and disease is a collection of articles from Nature Reviews Endocrinology and Nature Reviews Rheumatology on the latest advances in the bone field.
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Designing Bone Healing Therapies That Better Mimic Regeneration

Designing Bone Healing Therapies That Better Mimic Regeneration | Osteoporosis New drugs Review | Scoop.it
The range of biomimetic approaches to promote bone growth that are at the core of current bone healing therapies need to more closely emulate natural regenerative mechanisms. A review of biomimetic strategies to help heal bone defects, with an emphasis on cell transplantation, is published in BioResearch Open Access, a peer-reviewed open access journal from Mary Ann Liebert, Inc., publishers. The article is available free on the BioResearch Open Access website.
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BMPs and Biologic Materials in Spine Surgery

BMPs and Biologic Materials in Spine Surgery | Osteoporosis New drugs Review | Scoop.it
There has been a great deal of controversy regarding the use of BMP in spine surgery. A practicing spine surgeon and leader in the field of biologic materials, answers our questions in the insightful interview.
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Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo

Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo | Osteoporosis New drugs Review | Scoop.it
In the clinic, bone defects resulting from infections, trauma, surgical resection and genetic malformations remain a significant challenge.
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Frontiers | Ameloblastin Peptides Modulates the Osteogenic Capacity of Human Mesenchymal Stem Cells | Craniofacial Biology and Dental Research

Frontiers | Ameloblastin Peptides Modulates the Osteogenic Capacity of Human Mesenchymal Stem Cells | Craniofacial Biology and Dental Research | Osteoporosis New drugs Review | Scoop.it
During amelogenesis the extracellular enamel matrix protein AMBN is quickly processed into 17 kDa (N-terminus) and 23 kDa (C-terminus) fragments. In particular, alternatively spliced regions derived by exon 5 / 6 within the N-terminus region are known to be critical in biomineralization. Human mesenchymal stem cells (hMSC) also express and secrete AMBN, but it is unclear if this expression has effects on the hMSC themselves. If, as suggested from previous findings, AMBN act as a signaling molecule, such effects could influence hMSC growth and differentiation, as well as promoting the secretion of other signaling proteins like cytokines and chemokines. If AMBN is found to modulate stem cell behavior and fate, it will impact our understanding on how extracellular matrix molecules can have multiple roles during development ontogenesis, mineralization and healing of mesenchymal tissues. Here we show that synthetic peptides representing exon 5 promote hMSC proliferation. Interestingly, this effect is inhibited by the application of a 15 aa peptide representing the alternatively spliced start of exon 6. Both peptides also influence gene expression of RUNX2 and osteocalcin, and promote calcium deposition in cultures, indicating a positive influence on the osteogenic capacity of hMSC. We also show that the full-length AMBN-WT and N-terminus region enhance the secretion of RANTES, IP-10, and IL-8. In contrast, the AMBN C-terminus fragment and the exon 5 deleted AMBN (DelEx5) have no detectable effects on any of the parameters investigated. These findings suggest the signaling effect of AMBN is conveyed by processed products, whereas the effect on proliferation is differentially modulated through alternative splicing during gene expression.
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Silver Ion-Coated Medical Devices Could Fight MRSA While Creating New Bone

Silver Ion-Coated Medical Devices Could Fight MRSA While Creating New Bone | Osteoporosis New drugs Review | Scoop.it
Methicillin-resistant Staphylococcus aureus (MRSA) infections are caused by a type of staph bacteria that has become resistant to the antibiotics used to
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UCLA researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

UCLA researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone | Osteoporosis New drugs Review | Scoop.it
The new protocol opens the door to researchers who want to make muscle, bone and cartilage cells in the lab; the scientists plan to study whether the metho
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FDA review of Flexion ZilrettaTM (FX006) NDA for osteoarthritis

FDA review of Flexion ZilrettaTM (FX006) NDA for osteoarthritis | Osteoporosis New drugs Review | Scoop.it
An Intra-articular, Extended-release Formulation of Triamcinolone Acetonide under Investigation for the Treatment of Osteoarthritis of the Knee Background In the 1950’s, intra-articular injection of a corticosteroid (in particular hydrocortisone acetate) became an accepted treatment for what at the time were termed “arthritic” joints. Over ensuing decades, various synthetic corticosteroids, including Triamcinolone acetonide, were approved by …
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FDA accepted for review an NDA for Zilretta (FX006) to treat osteoarthritis of the knee. Its PDUFA date is Oct. 6.

Zilretta™ (FX006) Zilretta™ (FX006), Flexion’s lead investigational drug candidate, was developed with the goal of enhancing the clinical effect of intra-articular corticosteroid treatment. Zilretta™ is an extended-release formulation of Triamcinolone acetonide designed to prolong local residence following intra-articular injection. Zilretta™ is formulated using proprietary microsphere technology combining Triamcinolone acetonide with a poly lactic-co-glycolic acid (PLGA) matrix. Zilretta™ has received Fast Track Designation from the FDA. This designation is given to a drug in clinical development that is intended to treat a serious condition and addresses unmet medical need. Implicit in the definition of unmet medical need is the potential to provide a benefit over that observed with available therapies. An NDA (New Drug Application) for FX006 was submitted to the FDA in December 2016.
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Novel Therapies for Postmenopausal Osteoporosis

Novel Therapies for Postmenopausal Osteoporosis | Osteoporosis New drugs Review | Scoop.it
KEY POINTS  Recently discovered mechanisms in the regulation of mineral metabolism have led to the development of new therapies for osteoporosis.  These developments have led to new classes of drugs for the treatment of osteoporosis.  Despite numerous advances over the past 2 decades, the search for newer therapies
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Endocrinology and Metabolism Clinics of North America Volume 46, Issue 1, March 2017, Pages 207–219
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Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid

Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid | Osteoporosis New drugs Review | Scoop.it
Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture.
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Towards better hip replacements | Newsroom - McGill University

Towards better hip replacements | Newsroom - McGill University | Osteoporosis New drugs Review | Scoop.it
Creating a Better #3DPrinted Hip Replacement #3DPrinting https://t.co/oXB97wk78D
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Falls - NHS Choices

Falls - NHS Choices | Osteoporosis New drugs Review | Scoop.it
Anyone can have a fall, but older people are more vulnerable and likely to fall, especially if they have a long-term health condition.
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Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbil... - PubMed - NCBI

Bone morphogenetic protein-2 enhances the osteogenic differentiation capacity of mesenchymal stromal cells derived from human bone marrow and umbil... - PubMed - NCBI | Osteoporosis New drugs Review | Scoop.it

Int J Mol Med. 2017 Feb 1. doi: 10.3892/ijmm.2017.2872. [Epub ahead of print]


Abstract Mesenchymal stromal cells (MSCs) are multipotent cells that can give rise to different cell types of the mesodermal lineages. They are powerful sources for cell therapy in regenerative medicine as they can be isolated from various tissues, and can be expanded and induced to differentiate into multiple lineages. Recently, the umbilical cord has been suggested as an alternative source of MSCs. Although MSCs derived from the umbilical cord can be induced to differentiate into osteoblasts with a phenotypic similarity to that of bone marrow-derived MSCs, the differentiation ability is not consistent. In addition, MSCs from the umbilical cord require a longer period of time to differentiate into osteoblasts. Previous studies have demonstrated the benefits of bone morphogenetic protein-2 (BMP-2) in bone tissue regeneration. In addition, several studies have supported the use of BMP-2 in periodontal regeneration, sinus lift bone-grafting and non-unions in oral surgery. Although the use of BMP-2 for bone tissue regeneration has been extensively investigated, the BMP-2-induced osteogenic differentiation of MSCs derived from the umbilical cord has not yet been fully examined. Therefore, in this study, we aimed to examine the effects of BMP-2 on the osteogenic differentiation of MSCs derived from umbilical cord compared to that of MSCs derived from bone marrow. The degree of osteogenic differentiation following BMP-2 treatment was determined by assessing alkaline phosphatase (ALP) activity, and the expression profiles of osteogenic differentiation marker genes, osterix (Osx), Runt-related transcription factor 2 (Runx2) and osteocalcin (Ocn). The results revealed that BMP-2 enhanced the osteogenic differentiation capacity of MSCs derived from both bone marrow and umbilical cord as demonstrated by increased ALP activity and the upregulation of osteogenic differentiation marker genes. The enhancement of the osteogenic differentiation capacity of MSCs by BMP-2 suggests that these MSCs may be used as alternative sources for bone engineering or cell therapy in regenerative medicine. PMID: 28204808 DOI: 10.3892/ijmm.2017.2872

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Leptin in the interplay of inflammation, metabolism and immune system disorders

Leptin in the interplay of inflammation, metabolism and immune system disorders | Osteoporosis New drugs Review | Scoop.it
Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.
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Leptin in the interplay of inflammation, metabolism and immune system disorders 

 Vanessa Abella, Morena Scotece, Javier Conde, Jesús Pino, Miguel Angel Gonzalez-Gay, Juan J. Gómez-Reino, Antonio Mera, Francisca Lago, Rodolfo Gómez & Oreste Gualillo

Nature Reviews Rheumatology 13, 100–109 (2017) doi:10.1038/nrrheum.2016.209 
Published online 05 January 2017 
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Effect of Radiotherapy on Painful Bone Metastases

Effect of Radiotherapy on Painful Bone Metastases | Osteoporosis New drugs Review | Scoop.it

This secondary analysis of a National Cancer Institute of Canada trial investigates quality of life at days 10 and 42 after radiotherapy with a bone metastases–


Question How soon after radiotherapy for painful bone metastases can an improvement in quality of life be expected? 


 Findings In this secondary analysis of 238 patients from the NCIC Clinical Trials Group Symptom Control Trial SC.23, responders to radiotherapy had significantly greater improvement in pain, pain characteristics, functional interference, and psychosocial aspects at day 10 and significant improvement in most domains of the European Organisation for Research and Treatment of Cancer Quality of Life Bone Metastases Module and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative at day 42 compared with nonresponders. 


Meaning Quality of life and pain may improve as early as 10 days after radiotherapy; thus, a single 8-Gy dose of radiotherapy for painful bone metastases should be offered to all patients, even those with poor survival. Abstract

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JAMA Oncology

Effect of Radiotherapy on Painful Bone Metastases 

Rachel McDonald, MD(C); Keyue Ding, PhD; Michael Brundage, MD, MSc; et al 

Original Investigation | February 9, 2017
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New Study Compares Bone-Inducing Properties of 3D-Printed Mineralized Scaffolds

New Study Compares Bone-Inducing Properties of 3D-Printed Mineralized Scaffolds | Osteoporosis New drugs Review | Scoop.it
A new study of bone formation from stem cells seeded on 3D-printed bioactive scaffolds combined with different mineral additives showed that some of the scaffold mineral composites induced bone-forming activity better than others. The properties and potential to use these bioactive scaffolds in bone regeneration applications are discussed in an article published in Tissue Engineering, Part A, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Tissue Engineering website until March 13, 2017.
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N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment

N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment | Osteoporosis New drugs Review | Scoop.it

Abstract N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA’s potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an ‘inactive’ drug-delivery vehicle.

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N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment 

Chafik Ghayor, Bebeka Gjoksi, Jing Dong, Barbara Siegenthaler, Amedeo Caflisch & Franz E. Weber

Scientific Reports 7, Article number: 42108 (2017) doi:10.1038/srep42108
Published online: 08 February 2017
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Scientists develop new stem cell technique for bone repair

Scientists develop new stem cell technique for bone repair | Osteoporosis New drugs Review | Scoop.it
Researchers have developed a method of repairing bone using a mix of stem cells and and a carbon material with photocatalytic properties.
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UW Scientists Find Key Cues to Regulate Bone-Building Cells

UW Scientists Find Key Cues to Regulate Bone-Building Cells | Osteoporosis New drugs Review | Scoop.it
The prospect of regenerating bone lost to cancer or trauma is a step closer to the clinic as University of Wisconsin-Madison scientists have identified two proteins found in bone marrow as key regulators of the master cells responsible for making new bone.
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Experiments in mice may help boost newly FDA-approved therapy for spinal muscular atrophy

Experiments in mice may help boost newly FDA-approved therapy for spinal muscular atrophy | Osteoporosis New drugs Review | Scoop.it
Johns Hopkins researchers along with academic and drug industry investigators say they have identified a new biological target for treating spinal muscular atrophy. They report they have evidence that an experimental medicin
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Promising results using silver-releasing scaffolds in MRSA infection of bone

Promising results using silver-releasing scaffolds in MRSA infection of bone | Osteoporosis New drugs Review | Scoop.it
Researchers developed a biocompatible scaffold capable of controlled-release of silver ions and have shown in a new study that it can inhibit infection of bone by methicillin-resistant Staphylococcus aureus, known as MRSA
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Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: a case report with a 5-year follow-up

Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: a case report with a 5-year follow-up | Osteoporosis New drugs Review | Scoop.it
The treatment of articular cartilage defects is a therapeutic challenge for orthopaedic surgeons. Furthermore, large osteochondral defects needs restoration of the underlying bone for sufficient biomechanical characteristics as well as the overlying cartilage. A symptomatic large osteochondral defect in the knee joint was restored using a composite of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) 0.5 x 107/ml and 4% hyaluronic acid (HA) hydrogel. Significant improvements in pain and function of the knee joint were identified by the evaluation at 12 months after surgery. A hyaline-like cartilage completely filled the defect and was congruent with the surrounding normal cartilage as revealed by magnetic resonance imaging (MRI), a second-look arthroscopy and histological assessment. The improved clinical outcomes maintained until 5.5 years. MRI also showed the maintenance of the restored bony and cartilaginous tissues. This case report suggests that the composite of allogeneic UCB-MSCs and HA hydrogel can be considered a safe and effective treatment option for large osteochondral defects of the knee.
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BONE
miR-106b promotes osteoporosis in mice

BONE<br/>miR-106b promotes osteoporosis in mice | Osteoporosis New drugs Review | Scoop.it
The microRNA miR-106b contributes to osteoporosis by negatively regulating osteoblast differentiation and bone formation via the bone morphogenic protein 2 (BMP2) signalling pathway, according to new research. In vitro, miR-106b negatively regulated osteogenic differentiation of mesenchymal stem cells. Mice with glucocorticoid-induced osteoporosis (GIOP) expressed higher levels of miR-106b than healthy…
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miR-106b promotes osteoporosis in mice 
 Joanna Collison 
Nature Reviews Rheumatology (2017) doi:10.1038/nrrheum.2017.11 Published online 02 February 2017
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Signal mingle: Micropatterns of BMP-2 and fibronectin on soft biopolymeric films regulate myoblast shape and SMAD signaling

Signal mingle: Micropatterns of BMP-2 and fibronectin on soft biopolymeric films regulate myoblast shape and SMAD signaling | Osteoporosis New drugs Review | Scoop.it
In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM).
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Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation

Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation | Osteoporosis New drugs Review | Scoop.it
Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Zi-Fei Zhou, Tuan-Wei Sun, Feng Chen, Dong-Qing Zuo, Hong-Sheng Wang, Ying-Qi Hua, Zheng-Dong Cai, Jun Tan
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.
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