A bifunctional MXene-modified scaffold for photothermal therapy and maxillofacial tissue regeneration

Oral squamous cell carcinoma is one of the most common malignant tumours in the oral and maxillofacial regions and is highly malignant and prone to recur despite the development of various effective treatments,including surgery and chemoradiotherapy.Actually,it is difficult to ensure the complete elimination of tumour cells,and maxillofacial bone defects caused by surgery are hard to heal by themselves.In addition,chemoradiotherapy can bring serious side-effects.Therefore,it is imperative to develop a postoperative therapy to kill residual squamous cancer cells and repair bone defects without any side-effects.Here,we prepared a 3D scaffold by a 3D printing technique and freeze-drying method,which contained collagen,silk and hydroxyapatite(CSH)and was functionalized with MXene nanosheets(M-CSH).The considerable photothermal effect with long-term stability can significantly kill squamous CAL-27 cancer cells in vitro and inhibit tumour growth in vivo,increasing the probability of the M-CSH scaffold being applied in the photothermal therapy of oral squamous cell carcinoma.Moreover,the cell proliferation-and osteogenic-related protein expression of mouse embryonic osteogenic precursors(MC3T3-E1)indicated excellent biocompatibility and osteogenic activity of M-CSH scaffolds.The good compression modulus(52.8362.25 kPa)and in vivo bone formation performance made it possible to be used as reconstructive materials for bone defects.This scaffold is likely promising in future tissue engineering,especially for the multifunctional treatment of maxillofacial tumours.

Phototheranostic Nanoagents for Imaging-Guided Treatment of Oral Cancer

Phototherapy showed almost a lack of drug resistance and,depending on the therapeutic effects of non-invasive light-stimulating photosensors.The side effects of phototherapy were greatly reduced compared to their traditional equivalents.Phototheranostic nanoagents had new properties in drug delivery,biocompatibility,targeting and response,in which traditional phototheranostic drugs can not possess.Recently,a large number of relevant studies have demonstrated that photodynamic therapy(PDT)in combination with other agents and image-guided multifunctional photothermal therapy(PTT)were well suited for the treatment of oral cancer.Through the design of the nanoagents,researchers have discovered various applications for phototherapy,such as targeted release of co-packaged drugs,multifunctional imaging for diagnosis and treatment combination,accurate targeting caused by nanocarriers,and synergistic chemotherapy with phototherapy.In this paper,we first reviewed the research related to phototheranostic nanoagents for image-guided treatment of oral cancer.We tried to introduce the design concept and the treatment effect by three parts of components of phototheranostic nanoagents,categories of phototheranostic nanoagents and application of phototheranostic nanoagents.It also provided a reference for nanomaterial development and clinical applications in research of oral cancer treatment.

PPAR-γactivation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources.However,the xenograft,suffered from immune rejection and ischemia-reperfusion injury(IRI),causes massive reactive oxygen species(ROS)expression and the subsequent cell apoptosis,leading to the xenograft failure.Our previous study found a positive role of PPAR-γ in antiinflammation through its immunomodulation effects,which inspires us to apply PPAR-γ agonist rosiglitazone(RSG)to address survival issue of xenograft with the potential to eliminate the excessive ROS.In this study,xenogenic bioroot was constructed by wrapping the dental follicle cells(DFC)with porcine extracellular matrix(p ECM).The hydrogen peroxide(H_(2)O_(2))-induced DFC was pretreated with RSG to observe its protection on the damaged biological function.Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level.SD rat orthotopic transplantation model and superoxide dismutase 1(SOD1)knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft.It showed that RSG pretreatment significantly reduced the adverse effects of H2O2on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage.In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency,maximumly maintaining the xenograft function.We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress(OS)microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

Effects of different aperture-sized type I collagen/silk fibroin scaffolds on the proliferation and differentiation of human dental pulp cells

This study aimed at evaluate the effects of different aperture-sized type I collagen/silk fibroin(CSF)scaffolds on the proliferation and differentiation of human dental pulp cells(HDPCs).The CSF scaffolds were designed with 3D mapping software Solidworks.Three different aperture-sized scaffolds(CSF1-CSF3)were prepared by low-temperature deposition 3D printing technology.The morphology was observed by scanning electron microscope(SEM)and optical coherence tomography.The porosity,hydrophilicity and mechanical capacity of the scaffold were detected,respectively.HDPCs(third passage,1105 cells)were seeded into each scaffold and investigated by SEM,CCK-8,alkaline phosphatase(ALP)activity and HE staining.The CSF scaffolds had porous structures with macropores and micropores.The macropore size of CSF1 to CSF3 was 421627 lm,579636 lm and 707643 lm,respectively.The porosity was 69.862.2%,80.162.8%and 86.563.3%,respectively.All these scaffolds enhanced the adhesion and proliferation of HDPCs.The ALP activity in the CSF1 group was higher than that in the CSF3 groups(P<0.01).HE staining showed HDPCs grew in multilayer within the scaffolds.CSF scaffolds significantly improved the adhesion and ALP activity of HDPCs.CSF scaffolds were promising candidates in dentine-pulp complex regeneration.

Characterization on Modification and Biocompatibility of PCL Scaffold Prepared with Near-field Direct-writing Melt Electrospinning

In this study,orthogonal experiments were designed to explore the optimal process parameters for preparing polycaprolactone(PCL)scaffolds by the near-field direct-writing melt electrospinning(NFDWMES)technology.Based on the optimal process parameters,the PCL scaffolds with different thicknesses,gaps and structures were manufactured and the corresponding hydrophilicities were characterized.The PCL scaffolds were modified by chitosan(CS)and hyaluronic acid(HA)to improve biocompatibility and hydrophilicity.Both Fourier transform infrared spectroscopy(FTIR)analysis and antibacterial experimental results show that the chitosan and hyaluronic acid adhere to the surface of PCL scaffolds,suggesting that the modification plays a positive role in biocompatibility and antibacterial effect.The PCL scaffolds were then employed as a carrier to culture cells.The morphology and distribution of the cells observed by a fluorescence microscope demonstrate that the modified PCL scaffolds have good biocompatibility,and the porous structure of the scaffolds is conducive to adhesion and deep growth of cells.

Characterization and evaluation of a femtosecond laser-induced osseointegration and an anti-inflammatory structure generated on a titanium alloy

Cell–material interactions during early osseointegration of the bone–implant interface are critical and involve crosstalk between osteoblasts and osteoclasts.The surface properties of titanium implants also play a critical role in cell–material interactions.In this study,femtosecond laser treatment and sandblasting were used to alter the surface morphology,roughness and wettability of a titanium alloy.Osteoblasts and osteoclasts were then cultured on the resulting titanium alloy disks.Four disk groups were tested:a polished titanium alloy(pTi)control;a hydrophilic micro-dislocation titanium alloy(sandblasted Ti(STi));a hydrophobic nano-mastoid Ti alloy(femtosecond laser-treated Ti(FTi));and a hydrophilic hierarchical hybrid micro-/nanostructured Ti alloy[femtosecond laser-treated and sandblasted Ti(FSTi)].The titanium surface treated by the femtosecond laser and sandblasting showed higher biomineralization activity and lower cytotoxicity in simulated body fluid and lactate dehydrogenase assays.Compared to the control surface,the multifunctional titanium surface induced a better cellular response in terms of proliferation,differentiation,mineralization and collagen secretion.Further investigation of macrophage polarization revealed that increased anti-inflammatory factor secretion and decreased proinflammatory factor secretion occurred in the early response of macrophages.Based on the above results,the synergistic effect of the surface properties produced an excellent cellular response at the bone–implant interface,which was mainly reflected by the promotion of early ossteointegration andmacrophage polarization.

An amelogenin-based peptide hydrogel promoted the odontogenic differentiation of human dental pulp cells

Amelogenin can induce odontogenic differentiation of human dental pulp cells(HDPCs),which has great potential and advantages in dentine-pulp complex regeneration.However,the unstability of amelogenin limits its further application.This study constructed amelogenin self-assembling peptide hydrogels(L-gel or D-gel)by heating-cooling technique,investigated the effects of these hydrogels on the odontogenic differentiation of HDPCs and explored the underneath mechanism.The critical aggregation concentration,conformation,morphology,mechanical property and biological stability of the hydrogels were characterized,respectively.The effects of the hydrogels on the odontogenic differentiation of HDPCs were evaluated via alkaline phosphatase activity measurement,quantitative reverse transcription polymerase chain reaction,western blot,Alizarin red staining and scanning electron microscope.The mechanism was explored via signaling pathway experiments.Results showed that both the L-gel and D-gel stimulated the odontogenic differentiation of HDPCs on both Day 7 and Day 14,while the D-gel showed the highest enhancement effects.Meanwhile,the D-gel promoted calcium accumulation and mineralized matrix deposition on Day 21.The D-gel activated MAPK-ERK1/2 pathways in HDPCs and induced the odontogenic differentiation via ERK1/2 and transforming growth factor/smad pathways.Overall,our study demonstrated that the amelogenin peptide hydrogel stimulated the odontogenic differentiation and enhanced mineralization,which held big potential in the dentine-pulp complex regeneration.