A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone.

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

Three-dimensional donor-acceptor conjugated porous polymers based on metal-porphyrin and triazine for highly effective photodegradation of organic pollutants in water.

Three-dimensional donor-acceptor (D-A) type conjugated porous polymers (CPPs) was designed and synthesized via imine condensation of copper tetraaminoporphyrin (CuTAPP) as donor and 1,3,5-tris-(4-formyl phenyl) triazine (TFPT) as acceptor, named as CuPT-CPP. The CuPT-CPP possesses a high specific surface area (73.7 m2/g) and excellent photophysical properties. The simultaneous introduction of the organometallic molecules and D-A structures in CuPT-CPP could be broadened the visible-light response range (400-800 nm) and facilitated efficient photogenerated carrier separation and transportation. As heterogeneous photocatalysts, CuPT-CPP has excellent photocatalytic performances under visible light irradiation, leading to excellent model pollutant rhodamine B degradation efficiency up to about 100% in 3 h, it has superb stability and reusability during the photocatalytic processes, and CuPT-CPP also exhibited broad substrate adaptability, which could photocatalytic degradation of methylene blue (MB), methyl orange (MO), and tetracycline hydrochloride (TC). This work indicates that three-dimensional D-A type porphyrin- and triazine-based CuPT-CPP has great potential in the practical application of photocatalysis.

Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites.

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

A Prospective Randomized Study for the Placement of Flexible Laryngeal Airway Mask with Two-Step of Jaw-Thrust Technique by Both Hands for Adults.

To investigate the effect of two-step of jaw-thrust technique on the placement of flexible laryngeal mask with both hands. 157 patients scheduled for functional endoscopic sinus surgery were divided into two groups using a random number table method: control group (group C, n = 78) and test group (group T, n = 79). After induction of general anesthesia, the traditional method was applied to insert the flexible laryngeal airway mask in group C, and the two-step of jaw-thrust technique with both hands by the nurse was applied to help place the laryngeal mask in group T. The success rate, alignment status, oropharyngeal leak pressure (OLP) of the laryngeal mask, soft tissue injury of the oropharyngeal cavity and postoperative sore throat, and the incidence of adverse airway event were recorded in both groups. Results: The success rate of the first placement of flexible laryngeal masks in group C and group T were 73.8% and 97.5%, and the final success rates were 97.5% and 98.7%, respectively. Compared with group C, the success rate of first placement in group T was higher, and the difference was statistically significant (P < 0.01). There was no significant difference in the final success rate between the two groups (P = 0.56). The alignment score showed that the placement of group T was better than that of group C, and the difference was statistically significant (P < 0.01). The OLP of group C was 22.1 ± 2.6 cmH2O, and the OLP of group T was 25.4 ± 3.8 cmH2O. The OLP of group T was significantly higher than that of group C (P < 0.01). The incidence of mucosal injury and postoperative sore throat in group T were 2.5% and 5.0%, which were significantly lower than that of 23.0% and 16.7% in group C (both P < 0.01). There was no adverse airway event in each group. Conclusion: The two-step of jaw-thrust technique with both hands can improve the success rate of the first placement of the flexible laryngeal mask and the positioning of the laryngeal mask, increase the sealing pressure of the laryngeal mask, and reduce the incidence of oropharyngeal soft tissue injury and postoperative pharyngeal pain.

Application of piezoelectric materials in the field of bone: a bibliometric analysis.

In the past 4 decades, many articles have reported on the effects of the piezoelectric effect on bone formation and the research progress of piezoelectric biomaterials in orthopedics. The purpose of this study is to comprehensively evaluate all existing research and latest developments in the field of bone piezoelectricity, and to explore potential research directions in this area. To assess the overall trend in this field over the past 40 years, this study comprehensively collected literature reviews in this field using a literature retrieval program, applied bibliometric methods and visual analysis using CiteSpace and R language, and identified and investigated publications based on publication year (1984-2022), type of literature, language, country, institution, author, journal, keywords, and citation counts. The results show that the most productive countries in this field are China, the United States, and Italy. The journal with the most publications in the field of bone piezoelectricity is the International Journal of Oral & Maxillofacial Implants, followed by Implant Dentistry. The most productive authors are Lanceros-Méndez S, followed by Sohn D.S. Further research on the results obtained leads to the conclusion that the research direction of this field mainly includes piezoelectric surgery, piezoelectric bone tissue engineering scaffold, manufacturing artificial cochleae for hearing loss patients, among which the piezoelectric bone tissue engineering scaffold is the main research direction in this field. The piezoelectric materials involved in this direction mainly include polyhydroxybutyrate valerate, PVDF, and BaTiO3.

A prospective randomized study for the placement of flexible laryngeal airway mask with two-step jaw-thrust technique by both hands for adults.

OBJECTIVE: A prospective, randomized, and controlled study was conducted to investigate the effect of two-step jaw-thrust technique on the placement of flexible laryngeal mask (FLMA) with both hands. METHODS: Between November 2019 and January 2020, 160 patients scheduled for functional endoscopic sinus surgery with general anesthesia were enrolled in this study and were divided into two groups (n=80 each) using a random number table method: control group (group C) and test group (group T). After the induction of general anesthesia, the traditional method was applied to insert the flexible laryngeal airway mask in patients of group C, and the two-step jaw-thrust technique with both hands by the nurse was applied to help place the laryngeal mask in patients of group T. The success rate, alignment status by fibroscope (FOB) score, oropharyngeal leak pressure (OLP) of the laryngeal mask, oropharyngeal cavity soft tissue injury and postoperative sore throat, and the incidence of adverse airway event were compared between the two groups. (The registry of clinical trial: Chinese Clinical Trial Register, ChiCTR2100053017, https://www.chictr.org.cn). RESULTS: 78 patients in group C and 79 patients in group T were in includedfinal analysis. The success rates of the first placement of flexible laryngeal masks in patients of group C and group T were 73.81% and 97.52%, respectively. The final success rates were 97.52% and 98.81%, respectively. The success rate of first placement in group T was significantly higher than that of group C. There was no significant difference in the final success rate between the two groups (P=0.561). The alignment score showed that the placement of group T was significantly better than that of group C. The OLP of group T (25.43±3.82 cm) was significantly higher than that of group C (22.13±2.62 cm). The incidences of mucosal injury and postoperative sore throat in group T were 2.52% and 5.01%, which were significantly lower than those of 23.02% and 16.72% in group C. There was no adverse airway event in each group. CONCLUSION: The two-step jaw-thrust technique with both hands can improve the success rate of the first placement of the flexible laryngeal mask and the positioning of the laryngeal mask, increase the sealing pressure of the laryngeal mask, and reduce the incidence of oropharyngeal soft tissue injury and postoperative pharyngeal pain.

Biological Fixation of Bioactive Bone Cement in Vertebroplasty: The First Clinical Investigation of Borosilicate Glass (BSG) Reinforced PMMA Bone Cement.

PMMA bone cement has been clinically used for decades in vertebroplasty due to its high mechanical strength and satisfactory injectability. However, the interface between bone and PMMA is fragile and more prone to refracture in situ because PMMA lacks a proper biological response from the host bone with minimal bone integration and dense fibrous tissue formation. Here, we modified PMMA by incoporating borosilicate glass (BSG) with a dual glass network of [BO3] and [SiO4], which spontaneously modulates immunity and osteogenesis. In particular, the BSG modified PMMA bone cement (abbreviated as BSG/PMMA cement) provided an alkaline microenvironment that spontaneously balanced the activities between osteoclasts and osteoblasts. Furthermore, the trace elements released from the BSGs enhanced the osteogenesis to strengthen the interface between the host bone and the implant. This study shows the first clinical case after implantation of BSG/PMMA for three months using the dual-energy CT, which found apatite nucleation around PMMA instead of fibrous tissues, indicating the biological interface was formed. Therefore, BSG/PMMA is promising as a biomaterial in vertebroplasty, overcoming the drawback of PMMA by improving the biological response from the host bone.

Instant hydrogelation encapsulates drugs onto implants intraoperatively against osteoarticular tuberculosis.

Osteoarticular Tuberculosis (TB) is a challenging issue because of its chronicity and recurrence. Many drug delivery systems (DDSs) have been developed for general chemotherapy. Herein, we take advantage of instant hydrogelation to in situ encapsulate drugs onto implants intraoperatively, optimizing the drug release profile against osteoarticular TB. First-line chemodrugs, i.e. rifampicin (RFP) and isoniazid (INH) are firstly loaded on tricalcium phosphate (TCP). Then, the encapsulating hydrogel is fabricated by dipping in chitosan (CS) and ß-glycerophosphate (ß-GP) solution and heating at 80 °C for 40 min. The hydrogel encapsulation inhibits explosive drug release initially, but maintains long-term drug release (INH, 158 days; RFP, 53 days) in vitro. Therefore, this technique could inhibit bone destruction and inflammation from TB effectively in vivo, better than our previous ex situ prepared DDSs. The encapsulating technology, i.e. instant hydrogelation of drug-loaded implants, shows potential for regulating the type and ratio of drugs, elastic and viscous modulus of the hydrogel according to the state of illness intraoperatively for optimal drug release.

Effects of chitosan-coated pressed calcium sulfate pellets combined with recombinant human bone morphogenetic protein 2 on bone formation in femoral condyle-contained bone defects.

Calcium sulfate has a rapid degradation rate and little osteoinductive capability. Chitosan-coated pressed calcium sulfate pellets combined with recombinant human bone morphogenetic protein 2 (rhBMP-2) have been developed that exhibit decreased resorption speed and increased compressive strength and osteoinduction. A rabbit femoral condyle-contained bone defect model was used to study the restoration of the defects treated with chitosan-coated pressed calcium sulfate pellets combined with rhBMP-2, chitosan-coated pressed calcium sulfate pellets, and uncoated pressed calcium sulfate pellets. No pellets were implanted in the control group. After 3 and 13 weeks, the results indicated that chitosan-coated pressed calcium sulfate pellets exhibited relatively slower resorption that closely coincides with the growth rate of new bone and enhanced osteogenesis when combined with rhBMP-2.

[Application and research status of bioactive glass in bone repair].

OBJECTIVE: To summarize the clinical application and research status of bioactive glass (BAG) in bone repair. METHODS: The recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized. RESULTS: BAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made. CONCLUSION: BAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.

3D-Printed Titanium Cage with PVA-Vancomycin Coating Prevents Surgical Site Infections (SSIs).

Many coating materials have been studied to prevent surgical site infections (SSIs). However, antibacterial coating on surfaces show weak adhesion using the traditional titanium (Ti) cage, resulting in low efficacy for preventing SSIs after spinal surgery. Herein, a 3D-printed Ti cage combined with a drug-releasing system is developed for in situ drug release and bacteria killing, leading to prevention of SSIs in vitro and in vivo. First, a 3D-printed Ti cage is designed and prepared by the Electron Beam Melting (EBM) method. Second, polyvinyl alcohol (PVA) containing hydrophilic vancomycin hydrochloride (VH) is scattered across the surface of 3D-printed porous Ti (Ti-VH@PVA) cages. Ti-VH@PVA cages show an efficient drug-releasing profile and excellent bactericidal effect for three common bacteria after more than seven days in vitro. In addition, Ti-VH@PVA cages exhibit reliable inhibition of inflammation associated with Staphylococcus aureus and effective bone regeneration capacity in a rabbit model of SSIs. The results indicate that Ti-VH@PVA cages have potential advantages for preventing SSIs after spinal surgery.

Osteogenesis mechanism of chitosan-coated calcium sulfate pellets on the restoration of segmental bone defects.

A radial segmental defect model of a rabbit was used to study the restoration effect on defects treated with chitosan-coated pressed calcium sulfate pellets combined with recombinant human bone morphogenetic protein-2 (rhBMP-2), coated pressed calcium sulfate pellets, and uncoated pressed calcium sulfate pellets. Nothing was implanted in the control group. After 4, 8, and 12 weeks, the results indicated that coated pressed calcium sulfate pellets combined with rhBMP-2 and coated pressed calcium sulfate pellets facilitated new bone formation on defected bones and that, particularly, the coated pressed calcium sulfate pellets combined with rhBMP-2 was more effective than the coated pressed calcium sulfate pellet. Histologic and tetracycline fluorimetric findings showed that the osteogenesis mechanism of chitosan-coated pressed calcium sulfate pellets is membrane bone formation, and the pellets showed slightly slower resorption that closely coincides with the growth rate of new bone.

[Restoration of segmental bone defect by calcium sulfate pellet: experiment with rabbit].

OBJECTIVE: To compare the effects of different calcium sulfate pellets made by different methods in treating segmental defect of bone. METHODS: Eighty New Zealand white rabbits underwent cutting off a segment in the middle part of radius so as to establish models of radial segmental defect, and than were divided into 4 groups: Group A as control group, Group B with calcium sulfate pellet made by routine method implanted into the defect, Group C with chitosan coated pressed calcium sulfate pellet implanted into the defect, and Group D with chitosan coated pressed calcium sulfate pellet combined with recombinant human bone morphogenetic protein (rhBMP)-2 implanted into the defect: X-ray photography was done every 4 weeks to observe the new bone formation. Four, 8, and 12 weeks 5 rabbits from each group were killed. The defect segments with parts of normal bone at both ends were cut off to undergo fluorescence microscopy and biomechanic three point bending test. RESULTS: X-ray photography and histological examination showed that new bone formation of cortex and reconstruction of marrow cavity were seen in Groups D and C, especially in Group D. The new bone mineralization rate of Group D was significantly higher than that of Group C (P<0.05) which was significantly higher than that of Group B (P<0.01). The anti-bending strength ratio of Group D was (47.5%+/-2.1%, significantly higher than that of Group C [(39.6+/-1.7)%, F=125.3, P<0.01], and the anti-bending strength ratios of Groups D and C were both significantly higher than those of Groups B and A [(23.6+/-3.3)% and (21.3+/-2.7)%]. CONCLUSION: Chitosan coated pressed calcium sulfate pellet shows relatively higher anti-bending strength and slightly slower resorption that closely coincide with the growth rate of new bone. It can be used to restore segmental bone defect, and particularly when combined with rhBMP-2.

A self-digitization chip integrated with hydration layer for low-cost and robust digital PCR.

We present a self-discretization and zero-water-loss microfluidic digital PCR (dPCR) device to enable low-cost and robust quantitative nucleic acid assays. In this device, a thin void is integrated beneath the reaction chamber array. By utilizing the permeability of polydimethylsiloxane (PDMS) film, the integrated void serves a dual function: vacuum "accumulator" and hydration "reservoir". The combination of pre-stored pumping energy and water compensation for evaporation loss enables simple, robust and reliable single-DNA-molecule amplification and detection in 10,000 reactors of picoliter volume. Compared to the conventional degassing PDMS pumps, the vacuum accumulator exhibits superior performance due to more vacuum storage and shorter diffusion distance. We also evaluated the performance of the embedded hydration layer in suppressing evaporation loss at elevated temperatures, and verified that zero-water-loss could be achieved for all reaction chambers in our dPCR chip during thermal cycling. By performing quantitative detection of T790M DNA from 10 to 104 copies/µL, the proposed dPCR chip demonstrated high accuracy and excellent performance for the absolute quantification of the target gene with a dynamic range of 104. The simplicity and robustness of our dPCR chip make it well suited for low-cost molecular diagnostic assays under resource-limited settings.

Novel calcitonin gene-related peptide/chitosan-strontium-calcium phosphate cement: Enhanced proliferation of human umbilical vein endothelial cells in vitro.

Bone cement materials have some disadvantages, including slow degradation and no biological activity, which greatly weakens their clinical application. Therefore, the search for a multifunctional bioactive bone cement has become urgent. In this study, a novel bone cement sample of calcitonin gene-related peptide (CGRP)/chitosan-strontium (Sr)-calcium phosphate cement (CPC) was developed. The structure and morphology were observed by scanning electron microscope (SEM). The cytotoxicity and proliferation of CGRP/chitosan-Sr-CPC were also measured. The expression of CGRP receptor 1 was measured using an immunofluorescence assay. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were employed to quantify the VEGF mRNA and protein levels, respectively. Finally, the ability of the material to improve angiogenesis was assessed by using human umbilical vein endothelial cells (HUVECs) tube formation assay. The results showed that CGRP/Chitosan-Sr-CPC had the characteristics of a good orthopedic material without showing cell cytotoxicity to HUVECs. Meanwhile, CGRP/chitosan-Sr-CPC could release CGRP and enhance the proliferation of HUVECs via CGRP receptors. Moreover, CGRP/chitosan-Sr-CPC significantly upregulated the expression of the VEGF gene and protein in HUVECs, which might help improve the angiogenesis microenvironment. Besides, CGRP/chitosan-Sr-CPC could significantly improve angiogenesis of HUVECs. These findings provide new therapeutic material for the treatment of osteoporotic bone injury. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 19-28, 2019.

Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration.

It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks. This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were "switched off" when cultured in titrated material extracts with pH values higher than 7.8. To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast "switch on/off" behavior, the microenvironment boundary of the tested material was found to be 400 ± 50 µm, which is broader than the generally accepted value, 300 µm. Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone. To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.

A bioactive implant in situ and long-term releases combined drugs for treatment of osteoarticular tuberculosis.

Anti-tuberculosis chemotherapy with a long duration and adequate dosing is the mainstay for treatment of osteoarticular tuberculosis (TB). However, it is difficult for systemic administration to reach adequate local drug concentrations and achieve effective treatment. Herein, a hydroxyapatite (HA) scaffold implant combined with a drug-releasing system was designed to achieve in situ and long-term anti-TB drug release and highly efficient therapeutic activity in vitro and in vivo. The clinical anti-TB drugs hydrophilic isoniazid (INH) and hydrophobic rifampicin (RFP) were molecularly dispersed into polyvinyl alcohol (PVA) through immersion-curing techniques and were steadily adhered onto the surfaces of HA scaffolds (HA-drug@PVA). The HA-drug@PVA scaffolds showed a long-term, sustained drug release profile and killed proliferating Mycobacterium in vitro. In vivo experimental results revealed that the HA-drug@PVA scaffolds provided over 10- and 100-fold higher concentrations in muscles and bones, respectively, as well as a much lower concentration (<0.025) in blood. Furthermore, the HA-drug@PVA scaffold implanted in an osteoarticular TB rabbit model showed obvious bone regeneration and fusion due to the inhibition of TB-associated inflammatory changes. The excellent therapeutic effects indicate that in situ implant materials combined with a long-term drug release system are promising for the treatment of osteoarticular TB and other osteoarticular infections.

Lithium doped calcium phosphate cement maintains physical mechanical properties and promotes osteoblast proliferation and differentiation.

Calcium phosphate cement (CPC) has been widely used in bone tissue repairing due to its physical mechanical properties and biocompatibility. Addition of trace element to CPC has shown promising evidence to improve the physical properties and biological activities of CPC. Lithium (Li) has effect on osteoblast proliferation and differentiation. In this study, we incorporated Li to CPC and examined the physical properties of Li/CPC and its effect on osteoblast proliferation and differentiation. We found that Li doped CPC maintained similar setting time, pore size distribution, compressive strength, composition, and morphology as CPC without Li. Additionally, Li doped CPC improved osteoblast proliferation and differentiation significantly compared to CPC without Li. To our knowledge, our results, for the first time, show that Li doped CPC has beneficial effect on osteoblast in cell culture while keeps the excellent physical-mechanical properties of CPC. This study will lead to potential application of Li doped CPC in bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 944-952, 2017.

Acceleration of bone regeneration by activating Wnt/ß-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.

By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/ß-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/ß-catenin pathway in osteoporosis.