Osteoporotic Bone Defects Research Articles

3D printing and physicochemical and biological characterizations of gallium-containing magnesium/calcium phosphate ceramic scaffolds

In this study, gallium-containing magnesium/calcium phosphate ceramic scaffolds (G-MCP) were prepared by sintering the mixtures of gallium-doped tricalcium phosphate and trimagnesium phosphate at low temperatures (950 and 1000 °C), and their pore structure was formed by the extrusion-type 3D printing method. The G-MCP ceramic scaffolds were dominated by the gallium/magnesium-doped Ca3Mg3(PO4)4 phase. The G-MCP ceramic scaffolds sintered at 950 °C attained considerably high compressive strength (5.0–13.2 MPa) as well as porosity (63.7%–72.1%). When the sintering temperature increased to 1000 °C, the G-MCP ceramic scaffolds achieved tremendous increase in compressive strength (38.3–94.3 MPa), which was concomitant with significant decrease in porosity (46.2%–48.7%). Benefiting from the release of gallium, magnesium and calcium ions, the G-MCP ceramic scaffolds noticeably stimulated in vitro cell growth and osteoblastic differentiation, and distinctively obstructed the osteoclastic differentiation. The G-MCP ceramic scaffolds are promising for effectively treating the osteoporotic bone defects.

Liver-Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti-Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration.

Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti-inflammatory reserve (arginase-2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase-2 in the anti-inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti-inflammatory reserves in bone regeneration.

3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair.

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

A Recombinant Parathyroid Hormone-Related Peptide Locally Applied in Osteoporotic Bone Defect.

The local application of drug-loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self-assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone-related peptide-1 (PTHrP-1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti-OP bone repair material provides a theoretical basis for clinical translational applications.

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/β-Catenin Signaling Pathway.

In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, β-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, β-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/β-catenin signaling pathway.

Angiogenesis coupled with osteogenesis in a bone tissue engineering scaffold enhances bone repair in osteoporotic bone defects

Increased life expectancy has resulted in an increase in osteoporosis incidence worldwide. The coupling of angiogenesis and osteogenesis is indispensable for bone repair. Although traditional Chinese medicine (TCM) exerts therapeutic effects on osteoporosis, TCM-related scaffolds, which focus on the coupling of angiogenesis and osteogenesis, have not yet been used for the treatment of osteoporotic bone defects. Panax notoginseng saponin (PNS), the active ingredient of Panax notoginseng, was added to a poly (L-lactic acid) (PLLA) matrix. Osteopractic total flavone (OTF), the active ingredient of Rhizoma Drynariae, was encapsulated in nano-hydroxyapatite/collagen (nHAC) and added to the PLLA matrix. Magnesium (Mg) particles were added to the PLLA matrix to overcome the bioinert character of PLLA and neutralize the acidic byproducts generated by PLLA. In this OTF-PNS/nHAC/Mg/PLLA scaffold, PNS was released faster than OTF. The control group had an empty bone tunnel; scaffolds containing OTF:PNS = 100:0, 50:50, and 0:100 were used as the treatment groups. Scaffold groups promoted new vessel and bone formation, increased the osteoid tissue, and suppressed the osteoclast activity around osteoporotic bone defects. Scaffold groups upregulated the expression levels of angiogenic and osteogenic proteins. Among these scaffolds, the OTF-PNS (50:50) scaffold exhibited a better capacity for osteogenesis than the OTF-PNS (100:0 and 0:100) scaffolds. Activation of the bone morphogenic protein (BMP)-2/BMP receptor (BMPR)-1A/runt-related transcription factor (RUNX)-2 signaling pathway may be a possible mechanism for the promotion of osteogenesis. Our study demonstrated that the OTF-PNS/nHAC/Mg/PLLA scaffold could promote osteogenesis via the coupling of angiogenesis and osteogenesis in osteoporotic rats with bone defects, and activating the BMP-2/BMPR1A/RUNX2 signaling pathway may be an osteogenesis-related mechanism. However, further experiments are necessary to facilitate its practical application in the treatment of osteoporotic bone defects.

Methyltransferase-like 3 modulates osteogenic differentiation of adipose-derived stem cells in osteoporotic rats.

Osteoporosis (OP) is a metabolic bone disease involving reduced bone mass. Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Emerging evidence suggests that methyltransferase-like 3 (METTL3) plays a significant role in bone development and metabolism. Therefore, this study investigates changes to METTL3 in the osteogenic differentiation of adipose stem cells in osteoporotic rats (OP-ASCs) and explores ways to enhance their osteogenic ability. An animal model of osteoporosis was established by removing both ovaries in rats. Real-time PCR and western blotting were performed to detect the expression of METTL3 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Furthermore, alkaline phosphatase staining was used to confirm the osteogenic potential of stem cells. Mettl3 small interfering RNA and Mettl3 overexpression lentivirus were used to assess the role of METTL3 in osteogenic differentiation of ASCs and OP-ASCs. The osteogenic differentiation capacity and Mettl3 expression significantly decreased in OP-ASCs. Moreover, Mettl3 silencing down-regulated the osteogenic ability of ASCs, and overexpression of Mettl3 recovered the impaired osteogenic capacity in OP-ASCs in vitro. The Mettl3 expression levels and osteogenic potential of OP-ASCs decreased. However, overexpression of METTL3 rescued the osteogenic ability of OP-ASCs, providing a new target for treatment of osteoporotic bone defects.

Multifunctional Scaffold for Osteoporotic Pathophysiological Microenvironment Improvement and Vascularized Bone Defect Regeneration.

Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends to be more difficult due to suppressed osteogenic differentiation, hyperactive osteoclastogenesis, and impaired angiogenesis. Hence, a drug carrier system composed of gelatin-coated hollow mesoporous silica nanoparticles (HMSNs/GM) loaded with pro-osteogenic parathyroid (PTH) and anti-osteoclastogenic alendronate (ALN) is constructed and compounded into calcium magnesium phosphate cement (MCPC). The spatial-temporal release of ions and drugs, controllable degradation rate, and abundant pore structure of MCPC composites enhance osteoporotic bone regeneration in ovariectomized rats by accelerating vascularization, promoting osteogenic differentiation and mineralization, and inhibiting osteoclastogenesis and bone resorption. The MCPC/HMSNs@ALN-PTH/GM demonstrates a synergistic threefold effect on osteogenesis, osteoclastogenesis, and angiogenesis. It improves the osteoporotic pathophysiological microenvironment and promotes osteoporotic vascularized bone defect regeneration, holding huge potential for other functional biomaterials design and clinical management.

Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions.

Over-accumulation of reactive oxygen species (ROS) causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMMSCs). Selenium (Se) protects BMMSCs from oxidative stress-induced damage; however, it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs (OP-BMMSCs). In vitro treatment with sodium selenite (Na2SeO3) successfully improved the osteogenic differentiation of OP-BMMSCs, as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression. More importantly, Na2SeO3 restored the impaired mitochondrial functions of OP-BMMSCs, significantly up-regulated glutathione peroxidase 1 (GPx1) expression and attenuated the intracellular ROS and mitochondrial superoxide. Silencing of Gpx1 completely abrogated the protective effects of Na2SeO3 on mitochondrial functions of OP-BMMSCs, suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress. We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement (SF/CPC). After 8 weeks of implantation, Se-modified bone cement significantly promoted bone defect repair, evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats. These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway, and more importantly, supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats, representing a novel strategy for treating osteoporotic bone fractures or defects.

Electrospun naringin-loaded microsphere/sucrose acetate isobutyrate system promotes macrophage polarization toward M2 and facilitates osteoporotic bone defect repair.

Repairing osteoporotic bone defects is still a major clinical challenge. Recent studies have revealed that immune response is also essential in osteogenesis. The intrinsic inflammatory response of the host, especially the M1/M2 polarization status and inflammatory secretory function of macrophages, can directly affect osteogenic differentiation. Therefore, in this study, an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate (Ng-m-SAIB) system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects. The results of both in vitro and in vivo experiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2, thereby forming a favorable microenvironment for osteogenesis. The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of the osteoporotic model mouse (the senescence-accelerated mouse-strain P6). Together, these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favorable osteo-immunomodulatory effects.

Melatonin Repairs Osteoporotic Bone Defects in Iron-Overloaded Rats through PI3K/AKT/GSK-3β/P70S6k Signaling Pathway.

It was found recently that iron overload can cause osteoporosis in rats. Through in vitro and in vivo experimentations, the purpose of the present study was to validate and confirm the inhibitory effects of melatonin on iron death of osteoporosis and its role in bone microstructure improvements. Melatonin (100 mol/L) was administered to MC3T3-E1 cells induced by iron overload in vitro for 48 hours. The expression of cleaved caspase-3 and cleaved PARP and the production of ROS (reactive oxygen species) and mitochondrial damage were all exacerbated by iron overload. On the other hand, melatonin restored these impacts in MC3T3-E1 cells produced by iron overload. By evaluating the expression of PI3K/AKT/GSK-3β/P70S6k signaling pathway-related proteins (RUNX2, BMP2, ALP, and OCN) using RT-PCR and Western blot, osteogenic-related proteins were identified. Alizarin red S and alkaline phosphatase were utilized to evaluate the osteogenic potential of MC3T3-E1 cells. Melatonin significantly improved the osteogenic ability and phosphorylation rates of PI3K, AKT, GSK-3β, and P70S6k in iron overload-induced MC3T3-E1 cells. In vivo, melatonin treated iron overload-induced osteoporotic bone defect in rats. Rat skeletal microstructure was observed using micro-CT and bone tissue pathological section staining. ELISA was utilized to identify OCN, PINP, CTX-I, and SI in the serum of rats. We discovered that melatonin increased bone trabecular regeneration and repair in osteoporotic bone defects caused by iron overload. In conclusion, melatonin enhanced the osteogenic ability of iron overload-induced MC3T3-E1 cells by activating the PI3K/AKT/GSK-3β/P70S6k signaling pathway and promoting the healing of iron overload-induced osteoporotic bone defects in rats.

Promotion of osteoporotic bone healing by a tannic acid modified strontium-doped biomimetic bone lamella with ROS scavenging capacity and pro-osteogenic effect

The impaired osteogenic ability and excessive accumulation of reactive oxygen species (ROS) under osteoporosis severely weaken repair performance of biomimetic bone grafts. Currently, biomimetic bone grafts, capable of highly simulating bone hierarchy, could remarkably promote bone regeneration without systemic disease. Decorating biomimetic bone grafts with bioactivities without compromising hierarchical biomimicry stands as a feasible approach to treat the osteoporotic bone defect. Herein, through mineralizing decellularized collagen lamellae via strontium (Sr)- amorphous calcium phosphate and further modifying with tannic acid (TA), TA modified Sr-doped biomimetic bone lamellae was engineered. The physicochemical properties, ROS scavenging capacity and pro-osteogenic effect on osteoporotic bone marrow mesenchymal stem cells of construct were systemically evaluated. The results showed that TA and Sr can be successfully decorated without impairing the nano- and micro-architecture of biomimetic bone lamellae. The construct not only exhibited a potent and long-standing performance to eliminate ROS, but also effectively fostered the proliferation and osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells under oxidative stress environment. After implantation in the critical-sized bone defect of osteoporotic rat, it potently facilitated bone regeneration via synergistically activating PI3K/AKT signaling pathway. Hence, this construct is projected to be candidate for further engineering biomimetic bone grafts with more complicated hierarchy for accelerated healing of the osteoporotic bone defect.

Expert consensus on the bone repair strategy for osteoporotic fractures in China.

Osteoporotic fractures, also known as fragility fractures, are prevalent in the elderly and bring tremendous social burdens. Poor bone quality, weak repair capacity, instability, and high failure rate of internal fixation are main characteristics of osteoporotic fractures. Osteoporotic bone defects are common and need to be repaired by appropriate materials. Proximal humerus, distal radius, tibia plateau, calcaneus, and spine are common osteoporotic fractures with bone defect. Here, the consensus from the Osteoporosis Group of Chinese Orthopaedic Association concentrates on the epidemiology, characters, and management strategies of common osteoporotic fractures with bone defect to standardize clinical practice in bone repair of osteoporotic fractures.

Bioactive Scaffold Fabricated by 3D Printing for Enhancing Osteoporotic Bone Regeneration.

We develop a poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP)-based scaffold through a three-dimensional (3D) printing technique incorporating icaritin (ICT), a unique phytomolecule, and secretome derived from human fetal mesenchymal stem cells (HFS), to provide mechanical support and biological cues for stimulating bone defect healing. With the sustained release of ICT and HFS from the composite scaffold, the cell-free scaffold efficiently facilitates the migration of MSCs and promotes bone regeneration at the femoral defect site in the ovariectomy (OVX)-induced osteoporotic rat model. Furthermore, mechanism study results indicate that the combination of ICT and HFS additively activates the Integrin–FAK (focal adhesion kinase)–ERK1/2 (extracellular signal-regulated kinase 1/2)–Runx2 (Runt-related transcription factor 2) axis, which could be linked to the beneficial recruitment of MSCs to the implant and subsequent osteogenesis enhancement. Collectively, the PLGA/TCP/ICT/HFS (P/T/I/S) bioactive scaffold is a promising biomaterial for repairing osteoporotic bone defects, which may have immense implications for their translation to clinical practice.

Nanofibrous polycaprolactone-polyethylene glycol-based scaffolds embedded with pamidronate: fabrication and characterization

The present study outlines the fabrication and characterization of pamidronate (PDS) embedded nanofibrous scaffolds based on polycaprolactone/polycaprolactone-polyethyleneglycol-polycaprolactone (PCL/CEC) blends for osteoporotic bone defect management. The electrospinning technique has been utilized to fabricate PDS-loaded scaffolds and the effect of PDS on blends was evaluated by analyzing the surface morphology, wettability, biodegradability, and in vitro cytocompatibility. In vitro studies using human osteosarcoma cell lines (hOS) showed the non-cytotoxic nature of the scaffolds. The fibroporous architecture of PCL/CEC-PDS scaffolds along with their appropriate mechanical properties and ability to support cell growth in vitro suggests their potential for osteoporotic bone defect management.

Monoporous Microsphere as a Dynamically Movable Drug Carrier for Osteoporotic Bone Remodeling.

To repair systematically osteoporotic bone defects, it is important to make an effort to both diminish osteoporosis and enhance bone regeneration. Herein, a specifically monoporous microsphere (MPM) carrier encapsulating dosage-sensitive and short half-time parathyroid hormone (PTH) is constructed to tackle the issue. Compared with conventional microsphere carriers involving compact, porous, and mesoporous microspheres, the MPM is desirable to achieve precisely in situ delivery and to minimize topical accumulation. The findings show that the PTH loaded inside MPMs can be gradually released from the single hole of MPMs to improve the initial drug concentration. Also, the MPMs can self-shift with the daily movement of experimental animals to effectively reduce the topical aggregation of released drugs in vitro. In vivo evaluation further confirms that the implant of MPMs-PTH plays a dual role in stimulating the regenerative repair of the cranial defect and relieving osteoporosis in the whole body. Consequently, the current work develops a dynamically movable drug delivery system to achieve precisely in situ delivery, minimize topical accumulation, and systematically repair osteoporotic bone defects.

Preparation and characterization of Sr-substituted hydroxyapatite/reduced graphene oxide 3D scaffold as drug carrier for alendronate sodium delivery

Due to the characteristics of bone metabolic microenvironment in the local area of osteoporotic bone defect, it is often difficult for ordinary bone repair materials to achieve satisfactory repair effect. In this study, a multifunctional Sr-substituted hydroxyapatite/reduced graphene oxide (Sr-HAp/RGO) 3D scaffold was fabricated by a one-step hydrothermal reduction method. Sr-HAp colloids with good dispersion stability were firstly prepared to prevent precipitation and aggregation during hydrothermal process. The Sr-HAp/RGO composite scaffold with porous structure has a high compressive strength due to the reinforcement of Sr-HAp nanoparticles. Alendronate sodium (ALN), a commonly used drug for the treatment of osteoporosis, can be effectively loaded on the Sr-HAp/RGO scaffold and released for a prolonged time. The as-prepared ALN-loaded Sr-HAp/RGO scaffold shows promising potential for osteoporotic bone defect repair.

PLGA Cage‐Like Structures Loaded with Sr/Mg‐Doped Hydroxyapatite for Repairing Osteoporotic Bone Defects

Front Cover: In this study, a kind of PLGA cage-like structures loaded with Sr- and Mg-doped HA (Sr/Mg@HA/PLGA-CAS) was prepared. The multifunctional Sr/Mg@HA/PLGA-CAS porous system improved cell adhesion, osteogenic differentiation and angiogenic differentiation. Meanwhile, Sr/Mg@HA/PLGA-CAS inhibited osteoclast differentiation, and had a potential contribution to the repair of osteoporotic bone defects. This is reported by Xingyu Chen, Jie Weng, and co-workers in article number 2200092.

SrFe12O19-doped nano-layered double hydroxide/chitosan layered scaffolds with a nacre-mimetic architecture guide in situ bone ingrowth and regulate bone homeostasis.

Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFe12O19 nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFe12O19-LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 ​MPa). The as-released Mg2+ ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway. In vivo, the Mg2+ ions released from the SrFe12O19-LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1β and TNF-α), while the as-released Sr2+ ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFe12O19-LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFe12O19-LDH/CS scaffolds. Hence, this study on multifunctional SrFe12O19-LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects.

Strontium‐Doped Hydroxyapatite Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Osteoporotic Rats through the CaSR‐JAK2/STAT3 Signaling Pathway

Self‐repair of critical bone defects from periodontitis, tumor resection, and trauma is difficult. Osteoporosis is an abnormal bone metabolism disease characterized by increased bone resorption, decreased bone formation, and decreased activity of bone marrow mesenchymal stem cells (BMSCs), which further inhibits the repair of bone defects. Improving the osteogenic ability of BMSCs after osteoporosis is an important step in treating osteoporotic bone defects. Hydroxyapatite (HA) with good biocompatibility is widely used in bone material research. HA and strontium‐doped hydroxyapatite (Sr‐HA) microspheres are synthesized following a hydrothermal method, and the characteristics and the ability of these microspheres are explored to promote osteogenesis. Further, the role of the calcium‐sensing receptor (CaSR) and Janus kinase 2 gene/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway in this process are investigated. The results show that Sr‐HA, rather than HA alone, significantly promote the osteogenic differentiation of BMSCs in vitro and bone formation in vivo. Further, the effect of promoting osteogenic differentiation is realized by activating the CaSR‐JAK2/STAT3 signaling pathway. Therefore, the study demonstrates that Sr‐HA is the better choice for restoring critical bone defects.