Advances in clinical applications of bioceramics in the new regenerative medicine era

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

RESEARCH ON AND DEVELOPMENT OF BIOCERAMICS(Ⅰ)

This article reviews and discusses the definition, classification, performance, properties of the bioce-ramics which began to be researched on and developed in seventies and has been applied to the medical clinic since then, and the present situation of research on and development of the biological requirement put forward to bioce-ramic performance by the biont and comes to that the bioce-ramics is the most promising biological material in the modern medical clinic application.

The Bisphosphonate Clodronate Modifying Hydroxyapatite Bioceramics for Bone Scaffold

To investigate the efficiency of clodronate modifying HA bioceramics,and to evaluate the effect of clodronate modifying HA bioceramics on the cells in vitro,clodronate modified the porous HA bioceramics for bone scaffold by chelation .The outermost layer of the specimens was analyzd by XPS and FI-IR ,The depth profile was investigated by the argon-ion sputtering method.The cell culture test was conducted using MC3T3-E1 osteoblastic cells,The cells were inoculated and cultured on the scaffolds.Morphological observation of the cells,MTT test and ALP activity test evaluated the cell attachment ,proliferation and activity on the scaffolds.The cell culture test in cell quantity and morphology indicated active proliferation of the cells on the scaffolds.The ALP activity of the cells cultured for 3d and 7d on clodronate-HA bioceramics was slightly higher than that on HA bioceramics ,but the difference was not signifcant,This result indicated that clodronate-HA bioeramics had favorable cytocompatibility to be used as bone scaffold with potential ability to improve asteogensis.

Evaluation of Bioactive Properties of α and β Wollastonite Bioceramics Soaked in a Simulated Body Fluid

Dense natural wollastonite bioceramics (CaSiO3) were prepared by a sintering method, varying the pressing load and sintering temperature, in order to obtain different phases of wollastonite, and different physical properties in the materials. The products were characterized by TGA-DTA, XRD, FT-IR, SEM-EDS, TEM and XPS techniques. The results indicate the presence of two polymorphic phases of wollastonite, the β-wollastonite and α-wollastonite with a transition temperature of the β phase to α phase at approximately 1250℃. These materials were soaked in a simulated body fluid (SBF) during 1, 2 and 3 weeks, to study their solubility and bioactivity. The effect of different wollastonite phases on the solubility of Ca and Si, as well as the capacity of producing layers of “newly formed apatite” on the surfaces of these materials in SBF solution were analyzed.

Bioceramics utilization for the repair of internal resorption of the root:A case report

BACKGROUND The objective of this work is displaying a successful treatment for an internal resorption case under operating microscope using bioceramic material.CASE SUMMARY Periapical radiograph showed radiolucent lesion representing large internal resorption of the root.The respective defect was obturated using endoscquence bioceramic material follow up at the month 18 after treatment revealed no abnormal finings clinically and radiographically.CONCLUSION New generations bioceramics have many advantages that internal root resorption cases can benefit from.The use of operating microscope helps to apply obturating materials with precision.However,long term study on a large sample is required in future studies.

RESEARCH AND DEVELOPMENT OF BIOCERAMICS(Ⅱ)

The article describes the performance, properties and application of bioceramics in the medical clinic and reviews and discusses the advance in the research into several typical bioceramics, such as aluminium oxide bioceramics, carbons, bioactive glassceramics, calcium phosphate bioceramics, bioceramic composite materials etc, and comes to that bioceramics is the most promising bioactive material in the modern medical clinic application.

In Vivo Preliminary Study on Bone Neoformation Behavior of Three Types of Calcium Phosphate Bioceramics

Calcium phosphate microporous bioceramics and biphasic compositions of hydroxyapatite and β-calcium phosphate, in the form of microporous granular biomaterials, are research topics and present themselves as potential orthopedic and biomedical applications in rebuilding and repairing maxillofacial bones and tooth structure. This is associated with the characteristics of microstructure, biocompatibility, bioactivity and bone conductivity properties which these materials offer when applied in vivo or in a simulation environment. This study aimed to assess the behavior of bone neoformation of three types of calcium phosphate biomaterials in in vivo tests with sheep within 60 and 90 days, with the help of a scanning electron microscope. The biomaterials used were provided by the Group of Biomaterials at the Santa Catarina State University. The in vivo tests were carried out by generating, on sheep, tibial bone defects, three of which were filled with biomaterial (one different biomaterial for each bone defect generated), whilst the fourth received a bone fragment obtained during the generation of the defect in question, to serve as a control group. The scanning electron microscopy (SEM) technique was used for carrying out the preliminary characterization studies so as to observe new bone formation and osseointegration. The X-ray diffractometry (XRD) served as a support for the characterization of crystalline phases. The results obtained are encouraging and show that the biomaterials presented good performance in the process of bone formation, biomaterial osseointegration by a new tissue and bone mineralization.

Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration

Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a β-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.

Mn-containing bioceramics inhibit osteoclastogenesis and promote osteoporotic bone regeneration via scavenging ROS

Osteoporosis is caused by an osteoclast activation mechanism.People suffering from osteoporosis are prone to bone defects.Increasing evidence indicates that scavenging reactive oxygen species(ROS)can inhibit receptor activator of nuclear factorκB ligand(RANKL)-induced osteoclastogenesis and suppress ovariectomy-induced osteoporosis.It is critical to develop biomaterials with antioxidant properties to modulate osteoclast activity for treating osteoporotic bone defects.Previous studies have shown that manganese(Mn)can improve bone regeneration,and Mn supplementation may treat osteoporosis.However,the effect of Mn on osteoclasts and the role of Mn in osteoporotic bone defects remain unclear.In present research,a model bioceramic,Mn-containedβ-tricalcium phosphate(Mn-TCP)was prepared by introducing Mn intoβ-TCP.The introduction of Mn intoβ-TCP significantly improved the scavenging of oxygen radicals and nitrogen radicals,demonstrating that Mn-TCP bioceramics might have antioxidant properties.The in vitro and in vivo findings revealed that Mn^(2+)ions released from Mn-TCP bioceramics could distinctly inhibit the formation and function of osteoclasts,promote the differentiation of osteoblasts,and accelerate bone regeneration under osteoporotic conditions in vivo.Mechanistically,Mn-TCP bioceramics inhibited osteoclastogenesis and promoted the regeneration of osteoporotic bone defects by scavenging ROS via Nrf2 activation.These results suggest that Mn-containing bioceramics with osteoconductivity,ROS scavenging and bone resorption inhibition abilities may be an ideal biomaterial for the treatment of osteoporotic bone defect.

3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances

Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical strength,we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional(3D)printing.The experimental results showed that the secondary phase(i.e.10%magnesium substituting calcium silicate;CSM10)could readily improve the sintering property of the bioceramic composites(DIO/CSM10-x,x=0-30)with increasing the CSM10 content from 0%to 30%,and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds.Furthermore,the flexible strength(12.5 -30 MPa)and compressive strength(14-37 MPa)of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content,and the compressive strength of DIO/CSM10-30 showed a limited decay(from 37 MPa to 29 MPa)in the Tris buffer solution for a long time stage(8 weeks).These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic,especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.

Ion therapy of pulmonary fibrosis by inhalation of ionic solution derived from silicate bioceramics

Pulmonary fibrosis(PF)is a chronic and progressively fatal disease,but clinically available therapeutic drugs are limited due to efficacy and side effects.The possible mechanism of pulmonary fibrosis includes the damage of alveolar epithelial cells II(AEC2),and activation of immune cells such as macrophages.The ions released from bioceramics have shown the activity in stimulating soft tissue derived cells such as fibroblasts,endothelia cells and epithelia cells,and regulating macrophage polarization.Therefore,this study proposes an“ion therapy”approach based on the active ions of bioceramic materials,and investigates the therapeutic effect of bioactive ions derived from calcium silicate(CS)bioceramics on mouse models of pulmonary fibrosis.We demonstrate that silicate ions significantly reduce pulmonary fibrosis by simultaneously regulating the functions of AEC2 and macrophages.This result suggests potential clinical applications of ion therapy for lung fibrosis.

Colloidal forming of macroporous calcium pyrophosphate bioceramics in 3D-printed molds

A technique for colloidal forming of Ca2P2O7 macroporous bioceramics,based on low-pressure injection molding(LPIM)of a glycerol-water slip containing Ca2P2O7 and Ca(Н2PO4)2 into a plastic mold fabricated via FDM 3Dprinting,was proposed.Chemical reaction between the solid phases of the water containing slip-Ca2P2O7 and Ca(Н2PO4)2,resulting in brushite(CaHPO4·2H2O)formation,led to consolidation of the casting and preserved its complex architecture in the course of mold burning-out.Macroporous ceramics of Kelvin structure(70%macropores with the sizes from 2 up to 4 mm),based on a pre-defined composition with 10 wt%Ca(PO3)2 and sintered in liquid-phase regime,demonstrated a compressive strength of 1.4±0.1 MPa at a density of 22±2%.In vitro tests on bioactivity in SBF solution,as well as on resorption of the ceramics in model solution of citric acid,were carried out.

Preparation,Microstructure,and Properties of ZrO_(2)(3Y)/Al_(2)O_(3)Bioceramics for 3D Printing of All-ceramic Dental Implants by Vat Photopolymerization

Zirconia(ZrO_(2))ceramics have potential applications in the field of oral medicine owing to their desirable me-chanical properties,biocompatibility,chemical stability,and aesthetic properties.To realize clinical applications,ZrO_(2)(3Y)/Al_(2)O_(3)bioceramics for all-ceramic dental implants were prepared using vat photopolymerization 3D printing technology,and their process optimization,microstructure,mechanics,tribology,and biological proper-ties were studied.The results indicate that when the sintering temperature and holding time are 1600℃and 3 h,respectively,the density of ZrO_(2)(3Y)/Al_(2)O_(3)bioceramics reaches 98.79%,and its Vickers hardness,compressive strength,flexural strength,and fracture toughness also reach their maximum values.Furthermore,the in vitro sim-ulated oral environment wear tests showed that artificial saliva provides a lubricating effect on ZrO_(2)(3Y)/Al_(2)O_(3)bioceramics and improves wear resistance.The biosafety of ZrO_(2)(3Y)/Al_(2)O_(3)bioceramics was evaluated and ZrO_(2)(3Y)/Al_(2)O_(3)had no obvious cytotoxicity and promoted cell proliferation,growth,and adhesion.In addition,its surface has appropriate roughness and good wettability.In conclusion,ZrO_(2)(3Y)/Al_(2)O_(3)bioceramics prepared by vat photopolymerization are promising biomaterials with broad application prospects in dental restoration.

Bioinspired laminated bioceramics with high toughness for bone tissue engineering

For the research of biomaterials in bone tissue engineering,it is still a challenge to fabricate bioceramics that overcome brittleness whilemaintaining the great biological performance.Here,inspired by the toughness of naturalmaterials with hierarchical laminated structure,we presented a directional assembly-sintering approach to fabricate laminated MXene/calcium silicate-based(L-M/CS)bioceramics.Benefiting from the orderly laminated structure,the LM/CS bioceramics exhibited significantly enhanced toughness(2.23MPa·m^(1/2))and high flexural strength(145MPa),which were close to the mechanical properties of cortical bone.Furthermore,the L-M/CS bioceramics possessed more suitable degradability than traditional CaSiO_(3)bioceramics due to the newly formed CaTiSiO_(5)after sintering.Moreover,the L-M/CS bioceramics showed good biocompatibility and could stimulate the expression of osteogenesisrelated genes.The mechanism of promoting osteogenic differentiation had been shown to be related to theWnt signaling pathway.This work not only fabricated calciumsilicate-based bioceramics with excellentmechanical and biological properties for bone tissue engineering but also provided a strategy for the combination of bionics and bioceramics.

Microwave assisted synthesis & properties of nano HA-TCP biphasic calcium phosphate

Biphasic calcium phosphate （BCP） nanopowders were synthesized by using microwave and non-microwave irradiation assisted processes. The synthesized powders were pressed under a pressure of 90 MPa, and then were sintered at 1000-1200℃ for 1 h. The mechanical properties of the samples were investigated. The formed phases and microstructures were characterized by X-ray diffraction （XRD） and scanning electron microscopy （SEM）. The results showed that the synthesis time was shorter, along with a more homogeneous microstructure, when the microwave irradiation assisted method was applied. The compression strength and the Young＇s modulus of the samples synthesized with microwave irradiation were about 60 MPa and 3 GPa, but those of the samples synthesized without microwave irradiation were about 30 MPa and 2 GPa, respectively. XRD patterns of the microwave irradiation assisted and non-microwave irradiation assisted nanopowders showed the coexistence of hydroxyapatite （HA） and lricalcium phosphate （TCP） phases in the system.

Anterior Lumbar Intervertebral Fusion with Artificial Bone in Place of Autologous Bone

The feasibility of anterior lumbar intervertebral fusion with artificial bone in place of autogenous bone was investigated Porous hydroxyapatite(HA)/ZrO 2 ceramics loading bone morphogenetic protein (BMP) were implanted after removal of lumbar vertebral disc in rabbits The adjacent intervertebral discs were also removed by the same way and autogenous illic bone was implanted SEM observation and biomechanical test were carried out Compound bone had a bit lower osteoinductive activity than autogenous bone by SEM(Osteoindutive activity of artificial bone in 12 weeks was the same as that of autogenous bone in 9 weeks) Biomechanical test revealed that compound bone had lower anti-pull strength than autogenous bone ( P< 0 001), but there was no significant difference in anti-pull strength between compound bone at 12th week and autogenous bone at 9th week (P>0 05) It was concluded that compound bone could be applied for anterior spinal fusion, especially for those patients who can't use autogenous bone

Synthesis and Structural Characterization of Hydroxyapatite-Wollastonite Biocomposites, Produced by an Alternative Sol-Gel Route

Hydroxyapatite is a type of calcium phosphate-based material with great interest for biomedical applications, due to the chemical similarity between this material and the mineral part of human bone. However, synthetic hydroxyapatite is essentially brittle;the practice indicates that the use of hydroxyapatite without additives for implant production is not efficient, due to its low strength parameters. In the present work, biocomposites of hydroxyapatite-wollastonite were synthesized by an alternative sol-gel route, using calcium nitrate and ammonium phosphate as precursors of hydroxyapatite, and high purity natural wollastonite was added in ratios of 20, 50 and 80 percent by weight immersed in aqueous medium. Formation of hydroxyapatite occurs at a relatively low temperature of about 350?C, while the wollastonite remains unreacted. After that, these biocomposites were sintered at 1200?C for 5 h to produce dense materials. The characterization techniques demonstrated the presence of hydroxyapatite and wollastonite as unique phases in all products.

The influence of chromium ions on the growth of the calcium hydroxyapatite crystal

Hydroxyapatite (Ca10(PO4)6(OH)2) is widely used as bio-ceramic materials and as adsorbents for separation of bio-molecules. These materials have also been used as adsorbents for heavy metals, supports and as catalysts in oxidation and dehydrogenation reactions. The catalytic performance of these materials depend on the lattice substitution of Ca sites in Hydroxyapatite structure by varied cations as Na, Mg, Sr and Mn, which result in changes in various structural pro perties as crystallinity and morphology. Pure calcium hydroxyapatite (S1) and Cr loaded hydroxyl apatite (S2, S3, S4 and S5) of different chromium concentrations have been prepared by wet precipitated method. An in-vitro examination is essential to investigate the mechanism of the deficient HA and tissue interface reaction by preparing SBF (Simulated Body Fluid) through the elemental and chemical analysis of Ca, P and Cr. FTIR used to analyze the samples after incubation in SBF for 24 day. PH of the samples also was measured at the first period of immersion time. At high loading of chromium ions, the formation of carbonate apatite decrease. The concentrations of the chromium in the Cr_HA crystal during the soaking in SBF are very safe dose for human.

Solid reaction mechanism of CaHPO_4·2H_2O + CaCO_3 with and without yttria

The effect of yttria on the solid reaction mechanism of a CaHPO4·2H2O ＋ CaCO3 system at different temperatures was experimentally stud-ied. The samples with and without yttria were subjected to thermogravimetric/differential scanning calorimetry measurement. The samples were heat treated at the temperatures corresponding to the peaks on the DSC spectra, and the resulted phase compositions were identified by X-ray diffraction. The transformation mechanism was deduced by comparing the phases obtained at different temperatures. The results show that the transformations at below 1073 K are not affected by yttria, but all those at above 1073 K are completely altered. The formation tem-perature of hydroxyapatite decreases by 134 K, and the decomposition temperature increases by 38 K. The polymorphous transformation of Ca3（PO4）2 from β phase to α phase increases by 47 K. The thermodynamic properties of the transformations at above 1073 K are also modi-fied by the addition of yttria; that is, the endothermal peaks are substituted by exothermal peaks.

Study on Z-H/BMP Toughened Compound Artificial Bone and Its Osteogenesis

The purpose of this study was to find a kind of new artificial bone for anterior spinal fusion.ZrO 2 stabilized by Y 2O 3(Y-PSZ),porous hydroxyapatite(HA) and bone morphogenetic protein (BMP) were used to make artificial compound bone (Y 2O 3) ZrO 2-HA/BMP(Z-H/BMP),whose function was tested,microstructure and mineralogic composition constitution were analysised by SEM and XRD,and the corresponding animal tests were porformed.Osteogenesis of the material was observed by eyes,histology and SEM.Experimental results show that the component and ossific activity of Z-H/BMP were satisfactory.