A novel multilayer model with controllable mechanical properties for magnesium-based bone plates.

Proper mechanical properties are essential for the clinical application of magnesium-based implants. In the present work, a novel multilayer model composed of three layers with desirable features was developed. The modulus of the multilayer model can be adjusted by changing the thickness of each layer. To combine three layers and improve the corrosion resistance of the whole multilayer model, the polycaprolactone coating was employed. In the immersion test, pH values, the concentration of released magnesium ions, and weight loss indicate that the corrosion rate of multilayer models is considerable lower than that of the one-layer bare substrate. The three-point bending test, which is used to examine models' mechanical properties, shows that the flexural modulus of multilayer models is reduced effectively. In addition, the mechanical degradation of multilayer models is more stable, compared to the one-layer substrate.

Customized Additive Manufacturing in Bone Scaffolds-The Gateway to Precise Bone Defect Treatment.

In the advancing landscape of technology and novel material development, additive manufacturing (AM) is steadily making strides within the biomedical sector. Moving away from traditional, one-size-fits-all implant solutions, the advent of AM technology allows for patient-specific scaffolds that could improve integration and enhance wound healing. These scaffolds, meticulously designed with a myriad of geometries, mechanical properties, and biological responses, are made possible through the vast selection of materials and fabrication methods at our disposal. Recognizing the importance of precision in the treatment of bone defects, which display variability from macroscopic to microscopic scales in each case, a tailored treatment strategy is required. A patient-specific AM bone scaffold perfectly addresses this necessity. This review elucidates the pivotal role that customized AM bone scaffolds play in bone defect treatment, while offering comprehensive guidelines for their customization. This includes aspects such as bone defect imaging, material selection, topography design, and fabrication methodology. Additionally, we propose a cooperative model involving the patient, clinician, and engineer, thereby underscoring the interdisciplinary approach necessary for the effective design and clinical application of these customized AM bone scaffolds. This collaboration promises to usher in a new era of bioactive medical materials, responsive to individualized needs and capable of pushing boundaries in personalized medicine beyond those set by traditional medical materials.

Blending with transition metals improves bioresorbable zinc as better medical implants.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Iron oxide nanoparticle-based nanocomposites in biomedical application.

Iron-oxide-based biomagnetic nanocomposites, recognized for their significant properties, have been utilized in MRI and cancer treatment for several decades. The expansion of clinical applications is limited by the occurrence of adverse effects. These limitations are largely attributed to suboptimal material design, resulting in agglomeration, reduced magnetic relaxivity, and inadequate functionality. To address these challenges, various synthesis methods and modification strategies have been used to tailor the size, shape, and properties of iron oxide nanoparticle (FeONP)-based nanocomposites. The resulting modified nanocomposites exhibit significant potential for application in diagnostic, therapeutic, and theranostic contexts, including MRI, drug delivery, and anticancer and antimicrobial activity. Yet, their biosafety profile must be rigorously evaluated. Such efforts will facilitate the broader clinical translation of FeONP-based nanocomposites in biomedical applications.

Toward a Better Regeneration through Implant-Mediated Immunomodulation: Harnessing the Immune Responses.

Tissue repair/regeneration, after implantation or injury, involves comprehensive physiological processes wherein immune responses play a crucial role to enable tissue restoration, amidst the immune cells early-stage response to tissue damages. These cells break down extracellular matrix, clear debris, and secret cytokines to orchestrate regeneration. However, the immune response can also lead to abnormal tissue healing or scar formation if not well directed. This review first introduces the general immune response post injury, with focus on the major immune cells including neutrophils, macrophages, and T cells. Next, a variety of implant-mediated immunomodulation strategies to regulate immune response through physical, chemical, and biological cues are discussed. At last, various scaffold-facilitated regenerations of different tissue types, such as, bone, cartilage, blood vessel, and nerve system, by harnessing the immunomodulation are presented. Therefore, the most recent data in biomaterials and immunomodulation is presented here in a bid to shape expert perspectives, inspire researchers to go in new directions, and drive development of future strategies focusing on targeted, sequential, and dynamic immunomodulation elicited by implants.

In Vitro Osteocompatibility and Enhanced Biocorrosion Resistance of Diammonium Hydrogen Phosphate-Pretreated/Poly(ether imide) Coatings on Magnesium for Orthopedic Application.

Magnesium, as a biodegradable metal, is a promising candidate for biomedical applications. To modify the degradation behavior of magnesium and improve its osteocompatibility, chemical conversion and spin coating methods were combined to develop a diammonium hydrogen phosphate-pretreated/poly(ether imide) (DAHP/PEI) co-coating system. The diammonium hydrogen phosphate pretreatment was employed to enhance the attachment between PEI coatings and the magnesium substrate; meanwhile, it could serve as another bioactive and anticorrosion layer when PEI coatings break down. Surface characterization, electrochemical tests, and short-term immersion tests in DMEM were performed to evaluate DAHP/PEI coatings. Electrochemical measurements showed that DAHP/PEI coatings significantly improved the corrosion resistance of pure magnesium. No obvious changes of the chemical compositions of DAHP/PEI coatings occurred after 72 h of immersion in DMEM. An in vitro cytocompatibility study confirmed that viability and LDH activity of human osteoblast-like cells on DAHP/PEI coatings showed higher values than those on the DAHP-pretreated layer and pure magnesium. The DAHP-pretreated layer could still enhance the ALP activity of MG-63 cells after the degradation of PEI in DAHP/PEI coatings. Besides that, the in vitro cellular response to the treated magnesium was investigated to gain knowledge on the differentiation and proliferation of human adipose-derived stem cells (hADSCs). Cell distribution and morphology were observed by fluorescence and SEM images, which demonstrated that DAHP/PEI coatings facilitated cell differentiation and proliferation. The high level of C-terminals of collagen type I production of hADSCs on DAHP/PEI coatings indicated the potential of the coating for promoting osteogenic differentiation. Positive results from long-term cytocompatibility and proliferation tests indicate that DAHP/PEI coatings can offer an excellent surface for hADSCs.

Modification of in vitro degradation behavior of pure iron with ultrasonication treatment: Comparison of two different pseudo-physiological solutions.

An ultrasonication treatment is developed as an external method to control the degradation behavior of pure iron. Immersion tests (weight loss measurements) and electrochemical measurements were conducted in two different pseudo-physiological solutions, simulated body fluid (SBF) and Dulbecco's modified Eagle medium (DMEM) solution. By the comparison study in these two different solutions, more information and the mechanism of the degradation process can be revealed. Degradation morphologies (with and without ultrasonication treatment) were observed by scanning electron microscope (SEM), and degradation products on the surface were characterized by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). Moreover, the biocompatibility of iron surfaces after being ultrasonicated was evaluated. Ultrasonication was found to accelerate the degradation rate in DMEM, while it makes no difference in SBF solution; the origin of this different behavior is investigated and discussed. The parameters of the ultrasonication treatment, intensity and frequency, show an influence on the degradation rate. No adverse effects on the proliferation and adhesion of human osteoblast-like cells (MG-63) are observed on surfaces after ultrasonication treatment, as compared to bare iron. Based on these results, ultrasonication treatment is considered to have high potential to control the biodegradation behavior of iron-based materials in an external and flexible manner.

Electrophoretic Deposition of Bioadaptive Drug Delivery Coatings on Magnesium Alloy for Bone Repair.

Biodegradable polymer coatings on magnesium alloys are attractive, as they can provide corrosion resistance as well as additional functions for biomedical applications, e.g., drug delivery. A gelatin nanospheres/chitosan (GNs/CTS) composite coating on WE43 substrate was fabricated by electrophoretic deposition with simvastatin (SIM) loaded into the GNs. Apart from a sustained drug release over 28 days, an anticorrosion behavior of the coated WE43 substrates was confirmed by electrochemical tests. Both the degradation and corrosion rates of the coated substrate were significantly minimized in contrast to bare WE43. The cytocompatibility of the coated samples was analyzed  both quantitatively and qualitatively. Additionally, the osteogenic differentiation of MC3T3-E1 cells on SIM-containing coatings was assessed by measuring the expression of osteogenic genes and related proteins, alkaline phosphatase (ALP) activity, and extracellular matrix mineralization, showing that the SIM-loaded composite coating could upregulate the expression of osteogenic genes and related proteins, promote ALP activity, and enhance extracellular matrix mineralization. In summary, the SIM-loaded GNs/CTS composite coatings were able to enhance the corrosion resistance of the WE43 substrate and promote osteogenic activity, thus demonstrating a promising coating system for modifying the surface of magnesium alloys targeted for orthopedic applications.

A novel local drug delivery system: Superhydrophobic titanium oxide nanotube arrays serve as the drug reservoir and ultrasonication functions as the drug release trigger.

A local drug delivery system consisting of superhydrophobic titanium oxide nanotube (S-TNTs) arrays and ultrasonic-controlled release trigger was developed in this work. Hydrophilic TNTs arrays are converted into superhydrophobic after being treated by 1H,1H,2H,2H- perfluorooctyl-triethoxysilane (POTS). S-TNTs arrays serving as a drug-carrying vehicle require no extra sealing treatment due to the excellent isolation effect from the trapped air layer on the surface. Different amounts of drugs could be loaded into S-TNTs arrays by control of the structure of arrays (including length and diameter of tubes) and the original amount of drug in the drug-loading solution. The relation between surface morphology of TNTs arrays and superhydrophobicity (isolation effect) was thoroughly investigated. To achieve a stimulus-responsive drug delivery system, ultrasonication was employed as an efficient drug release trigger. Trapped air layer could be selectively removed by ultrasonication, and therefore the loaded drug could be released in a multiple and controlled manner. Any drugs that can dissolve in nonpolar solutions are expected to be suitable for this local drug delivery system.

Accelerated Degradation Behavior and Cytocompatibility of Pure Iron Treated with Sandblasting.

Fe-based materials are of interest for use in biodegradable implants. However, their corrosion rate in the biological environment may be too slow for the targeted applications. In this work, sandblasting is applied as a successful surface treatment for increasing the degradation rate of pure iron in simulated body fluid. Two sandblasting surfaces with different roughness present various surface morphologies but similar degradation products. Electrochemistry tests revealed that sandblasted samples have a higher corrosion rate compared to that of bare iron, and even more noteworthy, the degradation rate of sandblasted samples remains significantly higher during long-term immersion tests. On the basis of our experimental results, the most plausible reasons behind the fast degradation rate are the special properties of sandblasted surfaces, including the change of surface composition (for the early stage), high roughness (occluded surface sites), and high density of dislocations. Furthermore, the cytocompatibility was studied on sandblasting surfaces using human osteoblast-like cells (MG-63) by indirect and direct contact methods. Results revealed that sandblasting treatment brings no adverse effect to the growth of MG-63 cells. This work demonstrates the significant potential of sandblasting for controlling the degradation behavior of iron-based materials for biomedical applications.

Effect of the physiological stabilization process on the corrosion behaviour and surface biocompatibility of AZ91D magnesium alloy.

A promising pretreatment method for reducing the electrochemical activity of the magnesium alloy matrix beneath coatings is reported. The physiological stabilization process takes advantage of the localized micro-galvanic corrosion for transforming regions with high activity into a physiological stabilization layer, which can be converted into a protective coating by hydrothermal treatment. Electrochemical and immersion tests revealed that the corrosion resistance of treated AZ91D magnesium alloy was improved. In the cell viability test, the physiological stabilization-hydrothermal samples showed good cell viability for human embryonic kidney (HEK) 293 cells.

Novel method for controllable fabrication of a superhydrophobic CuO surface on AZ91D magnesium alloy.

A novel method for controllable fabrication of a superhydrophobic CuO surface on AZ91D magnesium alloy is reported in this paper. Hierarchical structure composed of micro/nano-featherlike CuO was obtained by electrodeposition of Cu-Zn alloy coating and subsequently an electrochemical anodic treatment in alkaline solution. After modification with lauric acid, the surface became hydrophobicity/superhydrophobicity. The formation of featherlike CuO structures was controllable by varying the coating composition. By applying SEM, ICP-AES, and water contact angle analysis, the effects of coating composition on the surface morphology and hydrophobicity of the as-prepared surfaces were detailedly studied. The results indicated that at the optimal condition, the surface showed a good superhydrophobicity with a water contact angle as high as 155.5 ± 1.3° and a sliding angle as low as about 3°. Possible growth mechanism of featherlike CuO hierarchical structure was discussed. Additionally, the anticorrosion effect of the superhydrophobic surface was studied by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurements. The interface model for anticorrosion mechanism of superhydrophobic surface in corrosive medium was proposed. Besides, the mechanical stability test indicated that the resulting superhydrophobic surfaces have good mechanical stability.