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Staphylococcus aureus (S. aureus) is a major pathogen for osteomyelitis. Calcium phosphate bone cement (CPC) paste is promising for orthopedic uses. Nanostructured graphene oxide (GO) showed antibacterial effect on Gram-positive bacteria. However, there has been no report of incorporating GO into CPC. The objectives of this study were to (a) develop an injectable and mechanically strong CPC-chitosan paste containing GO and (b) investigate the inhibition of S. aureus infection and the promotion of human umbilical cord mesenchymal stem cells (hUCMSCs) for bone regeneration. Injectable CPC-chitosan-GO paste was fabricated. Flexural strength, elastic modulus, and work-of-fracture of the CPC-chitosan and CPC-chitosan-GO bars were evaluated. Antibacterial effects against S. aureus biofilms were determined. hUCMSC growth and viability on disks were investigated. CPC-chitosan-GO bars had a flexural strength of 7.2 ± 1.6 MPa, matching that of CPC-chitosan control without GO. CPC-chitosan-GO had strong antibacterial effects on S. aureus, with an inhibition zone of 55.2 ± 2.5 mm, greater than that of CPC-chitosan control (30.1 ± 2.0 mm) (p0.05). CPC-chitosan-GO had potent antibacterial activity on S. aureus biofilms in vitro (p0.05). The injectable and antibacterial CPC-GO paste had no toxic effect, yielding excellent hUCMSC growth and viability on disks. The CPC-chitosan-GO had injectability, good strength, strong antibacterial effects, and excellent stem cell attachment and growth. CPC-chitosan-GO is promising for dental, craniofacial, and orthopedic applications to control infections and good biocompatibility to support stem cell viability to enhance bone regeneration.

Fixed orthodontic treatments often lead to enamel demineralization and cause white spot lesions (WSLs). The aim of this study was to evaluate the mineralization degree of 2 types of WSLs based on ICDAS index and compare the remineralizing efficacy of 3 oral hygiene practices after 1 month and 3 months. 80 mild demineralized and 80 severe demineralized enamel specimens were randomized into three treatments: fluoride toothpaste (FT), fluoride varnish plus fluoride toothpaste (FV+FT), and CPP-ACP plus fluoride toothpaste (CPP-ACP+FT). Microhardness tester, DIAGNODent Pen 2190, and scanning electron microscope were used to evaluate the changes of mineralization degree. Both qualitative and quantitative indicators suggested that the mild and severe white spot lesions were different in the degree of mineralization. Severe WSLs demineralized much more seriously than mild lesions even after 3 months of treatment. Despite the variation in severity, both lesions had the same variation trend after each measure was applied: FT had weak therapeutic effect, FV + FT and CPP-ACP + FT were effective for remineralization. Their remineralizing efficacy was similar after 1 month, and combined use of CPP-ACP plus F toothpaste was more effective after 3 months. In order to fight WSLs, early diagnosis was of great importance, and examination of the tooth surface after air-dry for 5 seconds was recommended. Also, when WSLs were found, added remineralizing treatments were required.

Metformin, a first-line antidiabetic drug used by millions of patients, has been shown to have potential osteogenic properties. The present study was performed to test the hypothesis that clinically relevant doses of metformin promote the osteogenic differentiation and mineralization of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs). iPSC-MSCs were treated with metformin (10 μm) to assess cell viability, osteogenic differentiation, mineralization and activation of the LKB1/AMP-activated protein kinase (AMPK) signalling pathway, a surrogate marker of metformin action. To determine its potential application in MSC-based bone and periodontal tissue engineering, iPSC-MSCs were also treated with metformin when seeded on to calcium phosphate cement (CPC) scaffolds. Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin. Although metformin treatment did not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase activity, enhanced mineralized nodule formation and increased expression of osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and osterix. Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization. Moreover, metformin substantially increased mineralized nodule formation of iPSC-MSC seeded on CPC scaffolds. Collectively, functional OCT-expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in part mediated by the LKB1/AMPK pathway. Considering the widespread use of metformin in diabetics, this work may lead to novel tissue-engineering platforms where autogenous OCT-expressing iPSC-MSCs might be used to enhance bone and periodontal regeneration in diabetic patients prescribed with daily doses of metformin.

Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of co-culture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were co-cultured with four types of cell: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs) and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs). Constructs were implanted in 8 mm cranial defects of rats for 12 weeks. CPC without cells served as control 1. CPC with hBMSCs served as control 2. Microcapillary-like structures were successfully formed on CPC in vitro in all four co-cultured groups. Microcapillary lengths increased with time (p 0.05). Osteogenic and angiogenic gene expressions were highly elevated and mineralization by co-cultured cells increased with time (p 0.05). New bone amount and blood vessel density of co-cultured groups were much greater than controls (p 0.05) in an animal study. hUVECs co-cultured with hUCMSCs, hiPSC-MSCs and hESC-MSCs achieved new bone and vessel density similar to hUVECs co-cultured with hBMSCs (p 0.1). Therefore, hUCMSCs, hiPSC-MSCs and hESC-MSCs could serve as alternative cell sources to hBMSCs, which require an invasive procedure to harvest. In conclusion, this study showed for the first time that co-cultures of hUVECs with hUCMSCs, hiPSC-MSCs, hESC-MSCs and hBMSCs delivered via CPC scaffold achieved excellent osteogenic and angiogenic capabilities in vivo. The novel co-culture constructs are promising for bone reconstruction with improved angiogenesis for craniofacial/orthopaedic applications. Copyright © 2017 John WileySons, Ltd.

Orthodontic treatment is increasingly popular as people worldwide seek esthetics and better quality of life. In orthodontic treatment, complex appliances and retainers are placed in the patients’ mouths for at least one year, which often lead to biofilm plaque accumulation. This in turn increases the caries-inducing bacteria, decreases the pH of the retained plaque on an enamel surface, and causes white spot lesions (WSLs) in enamel. This article reviews the cutting-edge research on a new class of bioactive and therapeutic dental resins, cements, and adhesives that can inhibit biofilms and protect tooth structures. The novel approaches include the use of protein-repellent and anticaries polymeric dental cements containing 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); multifunctional resins that can inhibit enamel demineralization; protein-repellent and self-etching adhesives to greatly reduce oral biofilm growth; and novel polymethyl methacrylate resins to suppress oral biofilms and acid production. These new materials could reduce biofilm attachment, raise local biofilm pH, and facilitate the remineralization to protect the teeth. This novel class of dental resin with dual benefits of antibacterial and protein-repellent capabilities has the potential for a wide range of dental and biomedical applications to inhibit bacterial infection and protect the tissues.

Stem cell-based tissue engineering offers immense promise for bone regeneration. The objective of this study was to develop a self-setting, mannitol-containing calcium phosphate cement (CPC) encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs) for bone tissue engineering. hUCMSCs could be an inexhaustible and low-cost alternative to the gold-standard bone marrow MSCs, which require an invasive procedure to harvest. hUCMSCs were encapsulated in alginate beads and mixed into the CPC paste. Water-soluble mannitol porogen was incorporated into CPC to create macropores. The porosity was increased from 49% for the hUCMSC-encapsulating CPC to 64% after adding mannitol and absorbable-fibres (p0.05). Flexural strength of the construct was increased from 0.3 MPa to 2.0 MPa via fibres. Live cell percentage was80% for all constructs. The ALP and OC gene expressions were low at 1 day and greatly increased at 14 days. The constructs that contained mannitol had significantly higher ALP and OC expressions than that without mannitol. ALP activity of hUCMSCs inside CPC with mannitol and fibre was significantly higher than that without mannitol. At 14 days, mineralization by the encapsulated hUCMSCs was eight-fold higher than that at 1 day. In conclusion, a novel mannitol-containing porous CPC-hUCMSC construct was developed for bone tissue engineering. Its advantages include cell delivery inside a load-bearing CPC that has injectable and in situ setting capabilities. hUCMSCs inside CPC had good viability and successfully osteodifferentiated. The self-setting and strong hUCMSC-encapsulating CPC scaffold is promising for bone tissue engineering in a wide range of orthopaedic and craniofacial applications.

The need for bone repair has increased as the population ages. Non-rigid calcium phosphate scaffolds could provide compliance for micro-motions within the tissues and yet have load-supporting strength. The objectives of this study were to: (a) develop a non-rigid calcium phosphate cement (CPC) with microbeads and fibre reinforcement; and (b) investigate human umbilical cord mesenchymal stem cell (hUCMSC) proliferation, osteodifferentiation and mineralization on non-rigid CPC for the first time. Non-rigid CPC was fabricated by adding extra tetracalcium phosphate in the traditional CPC and by incorporating chitosan, absorbable fibres and hydrogel microbeads. The non-rigid CPC–microbead scaffold possessed a strain-at-failure of 10.7%, much higher than the traditional CPC's strain of 0.05% which is typical for brittle bioceramics. Flexural strength of non-rigid CPC–microbead was 4-fold that of rigid CPC–microbead scaffold, while work-of-fracture (toughness) was increased by 20-fold. The strength of non-rigid CPC–microbead–fibre scaffold matched that of cancellous bone. hUCMSCs on non-rigid CPC proliferated from 100 cells/mm2 at 1 day to 600 cells/mm2 at 8 days. Alkaline phosphatase, osteocalcin and collagen gene expressions of hUCMSCs were greatly increased, and the cells synthesized bone minerals. hUCMSCs on non-rigid CPC–microbead–fibre constructs had higher bone markers and more mineralization than those on rigid CPC controls. In conclusion, this study developed the first non-rigid, in situ-setting calcium phosphate–microbead–fibre scaffold with a strain-at-failure exceeding 10%. hUCMSCs showed excellent proliferation, osteodifferentiation and mineralization on non-rigid CPC scaffold. The novel non-rigid CPC-hUCMSC construct with good strength, high strain-at-failure and toughness, as well as superior stem cell proliferation, osteodifferentiation and mineralization, is promising for load-bearing bone regeneration applications. Copyright © 2012 John Wiley & Sons, Ltd.