Strontium and Copper Co-Doped Multifunctional Calcium Phosphates: Biomimetic and Antibacterial Materials for Bone Implants.

ß-tricalcium phosphate (ß-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped ß-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca9.5-xSrxCu(PO4)7 was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr2+ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu2+. Isomorphic substitution of Ca2+ → (Sr2+and Cu2+) expands the concentration limits of the existence of the solid solution with the ß-TCP structure. No additional phases were formed up to x = 4.5 in Ca9.5-xSrxCu(PO4)7. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca9.5-xSrxCu(PO4)7 powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca9.5-xSrxCu(PO4)7 were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca9.5-xSrxCu(PO4)7 renders them multifunctional materials suitable for bone substitutes.

New strontium-based coatings show activity against pathogenic bacteria in spine infection.

Infections of implants and prostheses represent relevant complications associated with the implantation of biomedical devices in spine surgery. Indeed, due to the length of the surgical procedures and the need to implant invasive devices, infections have high incidence, interfere with osseointegration, and are becoming increasingly difficult to threat with common therapies due to the acquisition of antibiotic resistance genes by pathogenic bacteria. The application of metal-substituted tricalcium phosphate coatings onto the biomedical devices is a promising strategy to simultaneously prevent bacterial infections and promote osseointegration/osseoinduction. Strontium-substituted tricalcium phosphate (Sr-TCP) is known to be an encouraging formulation with osseoinductive properties, but its antimicrobial potential is still unexplored. To this end, novel Sr-TCP coatings were manufactured by Ionized Jet Deposition technology and characterized for their physiochemical and morphological properties, cytotoxicity, and bioactivity against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538P human pathogenic strains. The coatings are nanostructured, as they are composed by aggregates with diameters from 90 nm up to 1 µm, and their morphology depends significantly on the deposition time. The Sr-TCP coatings did not exhibit any cytotoxic effects on human cell lines and provided an inhibitory effect on the planktonic growth of E. coli and S. aureus strains after 8 h of incubation. Furthermore, bacterial adhesion (after 4 h of exposure) and biofilm formation (after 24 h of cell growth) were significantly reduced when the strains were cultured on Sr-TCP compared to tricalcium phosphate only coatings. On Sr-TCP coatings, E. coli and S. aureus cells lost their organization in a biofilm-like structure and showed morphological alterations due to the toxic effect of the metal. These results demonstrate the stability and anti-adhesion/antibiofilm properties of IJD-manufactured Sr-TCP coatings, which represent potential candidates for future applications to prevent prostheses infections and to promote osteointegration/osteoinduction.

Exploring Borate-Modified Calcium Phosphate Ceramics: Antimicrobial Potential and Cytocompatibility Assessment.

Addressing periprosthetic infections, which present significant healing challenges that often require revision surgeries, necessitates the development of novel antibacterial materials and implants. Current research focuses on creating materials that hinder bacterial adhesion, colonization, and proliferation in surrounding tissues. Boron (B)-containing compounds are known for their antibacterial properties and potential in bone metabolism for regenerative medicine. In this study, we synthesized B-containing tricalcium phosphate (0.3B-TCP) with 1.1 wt.% B content via precipitation from aqueous solutions and sintering at 1100 °C. X-ray diffraction confirmed the ceramic's primary crystalline phase as ß-TCP, with B evenly distributed according to energy-dispersive spectroscopy data. Electron paramagnetic resonance (EPR) data verified stable paramagnetic borate anions, indicating successful BO33- substitution for phosphate groups. The microstructural properties of 0.3B-TCP ceramic were assessed before and after soaking in a saline solution. Its bending strength was approximately 30 MPa, and its porosity was about 33%. 0.3B-TCP ceramic demonstrated significant antimicrobial efficacy against various bacterial strains and a fungus. Cytotoxicity evaluation using equine adipose tissue-derived mesenchymal stem cells and osteogenic differentiation assessment were conducted. The combination of antibacterial efficacy and good cytocompatibility suggests 0.3B-TCP ceramic as a promising bone substitute material.

Polysaccharide Composite Alginate-Pectin Hydrogels as a Basis for Developing Wound Healing Materials.

This article presents materials that highlight the bioengineering potential of polymeric systems of natural origin based on biodegradable polysaccharides, with applications in creating modern products for localized wound healing. Exploring the unique biological and physicochemical properties of polysaccharides offers a promising avenue for the atraumatic, controlled restoration of damaged tissues in extensive wounds. The study focused on alginate, pectin, and a hydrogel composed of their mixture in a 1:1 ratio. Atomic force microscopy data revealed that the two-component gel exhibits greater cohesion and is characterized by the presence of filament-like elements. The dynamic light scattering method indicated that this structural change results in a reduction in the damping of acoustic modes in the gel mixture compared to the component gels. Raman spectroscopy research on these gels revealed the emergence of new bonds between the components' molecules, contributing to the observed effects. The biocompatibility of the gels was evaluated using dental pulp stem cells, demonstrating that all the gels exhibit biocompatibility.

Arthroscopic Treatment of a Subchondral Bone Cyst via Stem Cells Application: A Case Study in Equine Model and Outcomes.

Subchondral bone cysts in horses represent one of the main causes of lameness that can occur in different anatomical locations. The study describes the treatment in regenerative therapy of the intracystic implantation of adipose tissue mesenchymal stromal cells (AMSCs) included in platelet-rich plasma (PRP). The ability of AMSCs to differentiate in osteogenic cells was tested in vitro and in vivo. Given the aim to investigate the application of AMSCs in bone defects and orthopedic pathologies in horses, a four-year-old male thoroughbred racing horse that had never raced before was treated for lameness of the left hind leg caused by a cyst of the medial femoral condyle. The horse underwent a new surgery performed with an arthroscopic approach in which the cystic cavity was filled with AMSCs contained in the PRP. Radiographs were taken 3, 5, and 10 months after the surgery to assess the development of newly regenerated bone tissue in the gap left by the cyst. Twelve months after the operation and after six months of regular daily training, the horse did not show any symptoms of lameness and started a racing career. According to the study, the use of AMSCs and PRP suggests promising benefits for treating subchondral bone cysts.

In Vitro Studies Regarding the Effect of Cellulose Acetate-Based Composite Coatings on the Functional Properties of the Biodegradable Mg3Nd Alloys.

Magnesium (Mg) alloys are adequate materials for orthopedic and maxilo-facial implants due to their biocompatibility, good mechanical properties closely related to the hard tissues, and processability. Their main drawbacks are the high-speed corrosion process and hydrogen release. In order to improve corrosion and mechanical properties, the Mg matrix can be strengthened through alloying elements with high temperature-dependent solubility materials. Rare earth elements (RE) contribute to mechanical properties and degradation improvement. Another possibility to reduce the corrosion rate of Mg-based alloys was demonstrated to be the different types of coatings (bioceramics, polymers, and composites) applied on their surface. The present investigation is related to the coating of two Mg-based alloys from the system Mg3Nd (Mg-Nd-Y-Zr-Zn) with polymeric-based composite coatings made from cellulose acetate (CA) combined with two fillers, respectively hydroxyapatite (HAp) and Mg particles. The main functions of the coatings are to reduce the biodegradation rate and to modify the surface properties in order to increase osteointegration. Firstly, the microstructural features of the experimental Mg3Nd alloys were revealed by optical microscopy and scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy. Apart from the surface morphology revealed by SEM, the roughness and wettability of all experimental samples were evaluated. The corrosion behavior of the uncoated and coated samples of both Mg3Nd alloys was investigated by immersion testing and electrochemical testing using Simulated Body Fluid as the medium. The complex in vitro research performed highlights that the composite coating based on CA with HAp particles exhibited the best protective effect for both Mg3Nd alloys.

Magnetic Resonance-Based Analytical Tools to Study Polyvinylpyrrolidone-Hydroxyapatite Composites.

The synthesis of biocompatible and bioresorbable composite materials, such as a "polymer matrix-mineral constituent," stimulating the natural growth of living tissues and the restoration of damaged parts of the body, is one of the challenging problems in regenerative medicine and materials science. Composite films of bioresorbable polymer of polyvinylpyrrolidone (PVP) and hydroxyapatite (HA) were obtained. HA was synthesized in situ in the polymer solution. We applied electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) approaches to study the composite films' properties. The application of EPR in two frequency ranges allowed us to derive spectroscopic parameters of the nitrogen-based light and radiation-induced paramagnetic centers in HA, PVP and PVP-HA with high accuracy. It was shown that PVP did not significantly affect the EPR spectral and relaxation parameters of the radiation-induced paramagnetic centers in HA, while light-induced centers were detected only in PVP. Magic angle spinning (MAS) 1H NMR showed the presence of two signals at 4.7 ppm and -2.15 ppm, attributed to "free" water and hydroxyl groups, while the single line was attributed to 31P. NMR relaxation measurements for 1H and 31P showed that the relaxation decays were multicomponent processes that can be described by three components of the transverse relaxation times. The obtained results demonstrated that the applied magnetic resonance methods can be used for the quality control of PVP-HA composites and, potentially, for the development of analytical tools to follow the processes of sample treatment, resorption, and degradation.

Polyvinylpyrrolidone-Alginate Film Barriers for Abdominal Surgery: Anti-Adhesion Effect in Murine Model.

Surgical operations on the peritoneum are often associated with the formation of adhesions, which can interfere with the normal functioning of the internal organs. The effectiveness of existing barrier materials is relatively low. In this work, the effectiveness of soluble alginate-polyvinylpyrrolidone (PVP-Alg) and non-soluble Ca ion cross-linked (PVP-Alg-Ca) films in preventing these adhesions was evaluated. Experiments in vivo were performed on mice via mechanical injury to the adjacent peritoneum wall and the caecum, followed by the application of PVP-Alg or PVP-Alg-Ca films to the injured area. After 7 days, samples from the peritoneal wall and caecum were analyzed using histology and quantitative polymerase chain reaction (qPCR). It was shown that the expression of genes responsible for adhesion formation in the caecum in the PVP-Alg group was comparable to that in the control group, while in the PVP-Alg-Ca group, it increased by 5-10 times. These results were consistent with the histology: in the PVP-Alg group, the adhesions did not form, while in the PVP-Alg-Ca group, the adhesions corresponded to five points on the adhesion scale. Therefore, the formation of intraperitoneal adhesions can be effectively prevented by non-crosslinked, biodegradable PVP-Alg films, whereas cross-linked, not biodegradable PVP-Alg-Ca films cause inflammation and adhesion formation.

Polyvinylpyrrolidone-Alginate-Carbonate Hydroxyapatite Porous Composites for Dental Applications.

An alternative approach for the currently used replacement therapy in dentistry is to apply materials that restore tooth tissue. Among them, composites, based on biopolymers with calcium phosphates, and cells can be applied. In the present work, a composite based on polyvinylpyrrolidone (PVP) and alginate (Alg) with carbonate hydroxyapatite (CHA) was prepared and characterized. The composite was investigated by X-ray diffraction, infrared spectroscopy, electron paramagnetic resonance (EPR) and scanning electron microscopy methods, and the microstructure, porosity, and swelling properties of the material were described. In vitro studies included the MTT test using mouse fibroblasts, and adhesion and survivability tests with human dental pulp stem cells (DPSC). The mineral component of the composite corresponded to CHA with an admixture of amorphous calcium phosphate. The presence of a bond between the polymer matrix and CHA particles was shown by EPR. The structure of the material was represented by micro- (30-190 µm) and nano-pores (average 8.71 ± 4.15 nm). The swelling measurements attested that CHA addition increased the polymer matrix hydrophilicity by 200%. In vitro studies demonstrated the biocompatibility of PVP-Alg-CHA (95 ± 5% cell viability), and DPSC located inside the pores. It was concluded that the PVP-Alg-CHA porous composite is promising for dentistry applications.

Ion-Doped Calcium Phosphate-Based Coatings with Antibacterial Properties.

Ion-substituted calcium phosphate (CP) coatings have been extensively studied as promising materials for biomedical implants due to their ability to enhance biocompatibility, osteoconductivity, and bone formation. This systematic review aims to provide a comprehensive analysis of the current state of the art in ion-doped CP-based coatings for orthopaedic and dental implant applications. Specifically, this review evaluates the effects of ion addition on the physicochemical, mechanical, and biological properties of CP coatings. The review also identifies the contribution and additional effects (in a separate or a synergistic way) of different components used together with ion-doped CP for advanced composite coatings. In the final part, the effects of antibacterial coatings on specific bacteria strains are reported. The present review could be of interest to researchers, clinicians, and industry professionals involved in the development and application of CP coatings for orthopaedic and dental implants.

Antibacterial Composite Material Based on Polyhydroxybutyrate and Zn-Doped Brushite Cement.

A composite material based on electrospinning printed polyhydroxybutyrate fibers impregnated with brushite cement containing Zn substitution was developed for bone implant applications. Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy were applied for materials characterization. Soaking the composite in Ringer's solution led to the transformation of brushite into apatite phase, accompanied by the morphology changes of the material. The bending strength of the composite material was measured to be 3.1 ± 0.5 MPa. NCTC mouse fibroblast cells were used to demonstrate by means of the MTT test that the developed material was not cytotoxic. The behavior of the human dental pulp stem cells on the surface of the composite material investigated by the direct contact method was similar to the control. It was found that the developed Zn containing composite material possessed antibacterial properties, as testified by microbiology investigations against bacteria strains of Escherichia coli and Staphylococcus aureus. Thus, the developed composite material is promising for the treatment of damaged tissues with bacterial infection complications.

1H NMR and EPR Spectroscopies Investigation of Alginate Cross-Linking by Divalent Ions.

Alginate is a natural polymer widely applied in materials science, medicine, and biotechnology. Its ability to bind metal ions in order to form insoluble gels has been comprehensively used to create capsules for cell technology, drug delivery, biomedical materials, etc. To modify and predict the properties of cross-linked alginate, knowledge about the mechanism of alginate binding with metal ions and the properties of its gels is necessary. This article presents the results obtained by proton Nuclear Magnetic Resonance Spectroscopy for alginate containing calcium and strontium (alkaline earth metal diamagnetic) ions and by Electron Paramagnetic Resonance Spectroscopy for alginate with copper (Cu) and manganese (Mn) (transition metal paramagnetic) ions. It was found that in the case of calcium (Ca) and Mn ions, their concentration does not affect their distribution in the alginate structure and the cross-linking density. In the case of strontium (Sr) and Cu ions, their number affects the number of binding sites and, accordingly, the cross-linking density. Thus, the cross-linking of alginate depends mainly on the characteristics of specific cations, while the nature of the bond (ionic or coordination type) is less important.

Effect of Filler Types on Cellulose-Acetate-Based Composite Used as Coatings for Biodegradable Magnesium Implants for Trauma.

Magnesium alloys are considered one of the most promising materials for biodegradable trauma implants because they promote bone healing and exhibit adequate mechanical strength during their biodegradation in relation to the bone healing process. Surface modification of biodegradable magnesium alloys is an important research field that is analyzed in many publications as the biodegradation due to the corrosion process and the interface with human tissue is improved. The aim of the current preliminary study is to develop a polymeric-based composite coating on biodegradable magnesium alloys by the solvent evaporation method to reduce the biodegradation rate much more than in the case of simple polymeric coatings by involving some bioactive filler in the form of particles consisting of hydroxyapatite and magnesium. Various techniques such as SEM coupled with EDS, FTIR, and RAMAN spectroscopy, and contact angle were used for the structural and morphological characterization of the coatings. In addition, thermogravimetric analysis (TGA) was used to study the effect of filler particles on polymer thermostability. In vitro cytotoxicity assays were performed on MG-63 cells (human osteosarcomas). The experimental analysis highlights the positive effect of magnesium and hydroxyapatite particles as filler for cellulose acetate when they are used alone from biocompatibility and surface analysis points of view, and it is not recommended to use both types of particles (hydroxyapatite and magnesium) as hybrid filling. In future studies focused on implantation testing, we will use only CA-based composite coatings with one filler on magnesium alloys because these composite coatings have shown better results from the in vitro testing point of view for future potential orthopedic biodegradable implants for trauma.

Antimicrobial and Cell-Friendly Properties of Cobalt and Nickel-Doped Tricalcium Phosphate Ceramics.

ß-Tricalcium phosphate (ß-TCP) is widely used as bone implant material. It has been observed that doping the ß-TCP structure with certain cations can help in combating bacteria and pathogenic microorganisms. Previous literature investigations have focused on tricalcium phosphate structures with silver, copper, zinc, and iron cations. However, there are limited studies available on the biological properties of ß-TCP containing nickel and cobalt ions. In this work, Ca10.5-xNix(PO4)7 and Ca10.5-xCox(PO4)7 solid solutions with the ß-Ca3(PO4)2 structure were synthesized by a high-temperature solid-state reaction. Structural studies revealed the ß-TCP structure becomes saturated at 9.5 mol/% for Co2+ or Ni2+ ions. Beyond this saturation point, Ni2+ and Co2+ ions form impurity phases after complete occupying of the octahedral M5 site. The incorporation of these ions into the ß-TCP crystal structure delays the phase transition to the α-TCP phase and stabilizes the structure as the temperature increases. Biocompatibility tests conducted on adipose tissue-derived mesenchymal stem cells (aMSC) using the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay showed that all prepared samples did not exhibit cytotoxic effects. Furthermore, there was no inhibition of cell differentiation into the osteogenic lineage. Antibacterial properties were studied on the C. albicans fungus and on E. coli, E. faecalis, S. aureus, and P. aeruginosa bacteria strains. The Ni- and Co-doped ß-TCP series exhibited varying degrees of bacterial growth inhibition depending on the doping ion concentration and the specific bacteria strain or fungus. The combination of antibacterial activity and cell-friendly properties makes these phosphates promising candidates for anti-infection bone substitute materials.

Antimicrobial Cu-Doped TiO2 Coatings on the ß Ti-30Nb-5Mo Alloy by Micro-Arc Oxidation.

Among the different surface modification techniques, micro-arc oxidation (MAO) is explored for its ability to enhance the surface properties of Ti alloys by creating a controlled and durable oxide layer. The incorporation of Cu ions during the MAO process introduces additional functionalities to the surface, offering improved corrosion resistance and antimicrobial activity. In this study, the ß-metastable Ti-30Nb-5Mo alloy was oxidated through the MAO method to create a Cu-doped TiO2 coating. The quantity of Cu ions in the electrolyte was changed (1.5, 2.5, and 3.5 mMol) to develop coatings with different Cu concentrations. X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron and atomic force microscopies, contact angle, and Vickers microhardness techniques were applied to characterize the deposited coatings. Cu incorporation increased the antimicrobial activity of the coatings, inhibiting the growth of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa bacteria strains, and Candida albicans fungus by approximately 44%, 37%, 19%, and 41%, respectively. Meanwhile, the presence of Cu did not inhibit the growth of Escherichia coli. The hardness of all the deposited coatings was between 4 and 5 GPa. All the coatings were non-cytotoxic for adipose tissue-derived mesenchymal stem cells (AMSC), promoting approximately 90% of cell growth and not affecting the AMSC differentiation into the osteogenic lineage.

An in situ study of thermal crystallization of amorphous calcium phosphates.

The heat-induced crystallization of amorphous calcium phosphate (ACP) is an intriguing process not yet well comprehended. This is because most of the works on this topic are based on ex situ studies where the materials are characterized after the heat and cooldown cycles, thus missing transient structural changes. Here, we used time-resolved energy dispersive X-ray diffraction and infrared spectroscopy to study, for the first time, the thermal crystallization of ACP in situ. The thermal crystallization of two kinds of citrate-stabilized carbonated ACP was studied, as they are promising materials for the preparation of advanced bioceramics. The behavior of these samples was compared to that of two citrate-free ACPs, either doped or non-doped with carbonate ions. Our results evinced that several phenomena occur during ACP thermal annealing. Before crystallization, all ACP samples undergo a decrease in the short-range order process, followed by several internal reorganizations. We have assessed that differently from carbonate-free ACP, carbonated ACPs with and without citrate directly crystallize into a biomimetic poorly crystalline carbonated hydroxyapatite. Citrate-stabilized ACPs in comparison to citrate-free ACPs have a faster hydroxyapatite formation kinetics, which is due to their higher specific surface area. This work reveals the necessity and the potentialities of using in situ techniques to effectively probe complex processes such as the heat-induced crystallization of ACPs.

Strontium Substituted ß-Tricalcium Phosphate Ceramics: Physiochemical Properties and Cytocompatibility.

Sr2+-substituted ß-tricalcium phosphate (ß-TCP) powders were synthesized using the mechano-chemical activation method with subsequent pressing and sintering to obtain ceramics. The concentration of Sr2+ in the samples was 0 (non-substituted TCP, as a reference), 3.33 (0.1SrTCP), and 16.67 (0.5SrTCP) mol.% with the expected Ca3(PO4)2, Ca2.9Sr0.1(PO4)2, and Ca2.5Sr0.5(PO4)2 formulas, respectively. The chemical compositions were confirmed by the energy-dispersive X-ray spectrometry (EDX) and the inductively coupled plasma optical emission spectroscopy (ICP-OES) methods. The study of the phase composition of the synthesized powders and ceramics by the powder X-ray diffraction (PXRD) method revealed that ß-TCP is the main phase in all compounds except 0.1SrTCP, in which the apatite (Ap)-type phase was predominant. TCP and 0.5SrTCP ceramics were soaked in the standard saline solution for 21 days, and the phase analysis revealed the partial dissolution of the initial ß-TCP phase with the formation of the Ap-type phase and changes in the microstructure of the ceramics. The Sr2+ ion release from the ceramic was measured by the ICP-OES. The human osteosarcoma MG-63 cell line was used for viability, adhesion, spreading, and cytocompatibility studies. The results show that the introduction of Sr2+ ions into the ß-TCP improved cell adhesion, proliferation, and cytocompatibility of the prepared samples. The obtained results provide a base for the application of the Sr2+-substituted ceramics in model experiments in vivo.

Effect of the Antimicrobial Agents Peppermint Essential Oil and Silver Nanoparticles on Bone Cement Properties.

The main problems directly linked with the use of PMMA bone cements in orthopedic surgery are the improper mechanical bond between cement and bone and the absence of antimicrobial properties. Recently, more research has been devoted to new bone cement with antimicrobial properties using mainly antibiotics or other innovative materials with antimicrobial properties. In this paper, we developed modified PMMA bone cement with antimicrobial properties proposing some experimental antimicrobial agents consisting of silver nanoparticles incorporated in ceramic glass and hydroxyapatite impregnated with peppermint oil. The impact of the addition of antimicrobial agents on the structure, mechanical properties, and biocompatibility of new PMMA bone cements was quantified. It has been shown that the addition of antimicrobial agents improves the flexural strength of the traditional PMMA bone cement, while the yield strength values show a decrease, most likely because this agent acts as a discontinuity inside the material rather than as a reinforcing agent. In the case of all samples, the addition of antimicrobial agents had no significant influence on the thermal stability. The new PMMA bone cement showed good biocompatibility and the possibility of osteoblast proliferation (MTT test) along with a low level of cytotoxicity (LDH test).

Recent advances on the mechanical behavior of zinc based biodegradable metals focusing on the strain softening phenomenon.

Zinc based biodegradable metals (BMs) show great potential to be used in various biomedical applications, owing to their superior biodegradability and biocompatibility. Some high-strength (ultimate tensile strength > 600 MPa) Zn based BMs have already been developed through alloying and plastic working, making their use in load-bearing environments becomes a reality. However, different from Mg and Fe based BMs, Zn based BMs exhibit significant "strain-softening" effect that leads to limited uniform deformation. Non-uniform deformation is detrimental to Zn based devices or implants, which will possibly lead to unexpected failure. People might be misled by the considerable fracture elongation of Zn based BMs. Thus, it is important to specify uniform elongation as a term of mechanical requirements for Zn based BMs. In this review, recent advances on the mechanical properties of Zn based BMs have been comprehensively summarized, especially focusing on the strain softening phenomenon. At first, the origin and evaluation criteria of strain softening were introduced. Secondly, the effects of alloying elements (including element type, single or multiple addition, and alloying content) and microstructural characteristics (grain size, constituent phase, phase distribution, etc.) on mechanical properties (especially for uniform elongation) of Zn based BMs were summarized. Finally, how to get a good balance between strength and uniform elongation was generally discussed based on the service environment. In addition, possible ways to minimize or eliminate the strain softening effect were also proposed, such as controlling of twins, solute clusters, and grain boundary characteristics. All these items above would be helpful to understand the mechanical instability of Zn based BMs, and to make the full usage of them in the future medical device design. STATEMENT OF SIGNIFICANCE: Biodegradable metals (BMs) is a hotspot in the field of metallic biomaterials. Fracture elongation is normally adopted to quantify the deformability of Mg and Fe based BMs owing to their negligible necking strain, yet the strain softening would occur in Zn based BMs, which is extremely detrimental to performance of their medical device. In this review paper, a better understanding the mechanical performance of Zn-based BMs with the term "uniform elongation" instead of "fracture elongation" was depicted, and possible ways to minimize or eliminate the strain softening effect were also proposed, such as twins, solute clusters, self-stable dislocation network, and grain boundary characteristics. It would be helpful to understand the mechanical instability of Zn based BMs and making full usage of it in the future medical device design.

Mn-Containing Bioactive Glass-Ceramics: BMP-2-Mimetic Peptide Covalent Grafting Boosts Human-Osteoblast Proliferation and Mineral Deposition.

The addition of Mn in bioceramic formulation is gaining interest in the field of bone implants. Mn activates human osteoblast (h-osteoblast) integrins, enhancing cell proliferation with a dose-dependent effect, whereas Mn-enriched glasses induce inhibition of Gram-negative or Gram-positive bacteria and fungi. In an effort to further optimize Mn-containing scaffolds' beneficial interaction with h-osteoblasts, a selective and specific covalent functionalization with a bioactive peptide was carried out. The anchoring of a peptide, mapped on the BMP-2 wrist epitope, to the scaffold was performed by a reaction between an aldehyde group of the peptide and the aminic groups of silanized Mn-containing bioceramic. SEM-EDX, FT-IR, and Raman studies confirmed the presence of the peptide grafted onto the scaffold. In in vitro assays, a significant improvement in h-osteoblast proliferation, gene expression, and calcium salt deposition after 7 days was detected in the functionalized Mn-containing bioceramic compared to the controls.