Designing Better Cardiovascular Stent Materials - A Learning Curve.

Cardiovascular stents are life-saving devices and one of the top 10 medical breakthroughs of the 21st century. Decades of research and clinical trials have taught us about the effects of material (metal or polymer), design (geometry, strut thickness, and the number of connectors), and drug-elution on vasculature mechanics, hemocompatibility, biocompatibility, and patient health. Recently developed novel bioresorbable stents are intended to overcome common issues of chronic inflammation, in-stent restenosis, and stent thrombosis associated with permanent stents, but there is still much to learn. Increased knowledge and advanced methods in material processing have led to new stent formulations aimed at improving the performance of their predecessors but often comes with potential tradeoffs. This review aims to discuss the advantages and disadvantages of stent material interactions with the host within five areas of contrasting characteristics, such as 1) metal or polymer, 2) bioresorbable or permanent, 3) drug elution or no drug elution, 4) bare or surface-modified, and 5) self-expanding or balloon-expanding perspectives, as they relate to pre-clinical and clinical outcomes and concludes with directions for future studies.

Micro-/Nanotopography on Bioresorbable Zinc Dictates Cytocompatibility, Bone Cell Differentiation, and Macrophage Polarization.

Bioresorbable metals are quickly advancing in the field of regenerative medicine for their promises of tissue restoration without adverse consequences from their lifelong presence. Zn has recently risen to the top of bioresorbable metals with great potential as a medical implant. However, cell adhesion and colonization on the Zn substrate surface remains challenging, which could damper interfacial tissue-implant integration. Inspired by the fact that surface topography can regulate cell function and fate, we hypothesize that topography on bioresorbable Zn can dictate material biocompatibility, cell differentiation, and immunomodulation. To verify this, surface-engineered Zn plates with nano-, submicro-, and microtopographies were systematically investigated. The microscale topography exhibited increased adhesion, pronounced self-renewal, and enhanced osteogenic differentiation of bone cells as well as less macrophage inflammatory polarization, reduced platelet adhesion, and better hemocompatibility. Thus, surface topography could be a viable strategy to enhance bioresorbable Zn's biocompatibility and integration with surrounding tissues while reducing inflammation.

Porous zinc scaffolds for bone tissue engineering applications: A novel additive manufacturing and casting approach.

As a degradable metal, zinc (Zn) has attracted an immense amount of interest as the next generation of bioresorbable implants thanks to its modest corrosion rate and its vital role in bone remodeling, yet very few studies have thoroughly investigated its functionality as a porous implant for bone tissue engineering purposes. Zn bone scaffolds with two different pore sizes of 900 µm and 2 mm were fabricated using additive manufacturing-produced templates combined with casting. The compressive properties, corrosion rates, biocompatibility, and antibacterial performance of the bioscaffolds were examined and compared to a non-porous control. The resulting textured and porous Zn scaffolds exhibit a fully interconnected pore structure with precise control over topology. As pore size and porosity increased, mechanical strength decreased, and corrosion rate accelerated. Cell adhesion and growth on scaffolds were enhanced after an ex vivo pretreatment method. In vitro cellular tests confirmed good biocompatibility of the scaffolds. As porosity increased, potent antibacterial rates were also observed. Taken together, these results demonstrate that Zn porous bone scaffolds are promising for orthopedic applications.

Biocompatible High Entropy Alloys with Excellent Degradation Resistance in a Simulated Physiological Environment.

Bioimplants are susceptible to simultaneous wear and corrosion degradation in the aggressive physiological environment. High entropy alloys with equimolar proportion of constituent elements represent a unique alloy design strategy for developing bioimplants due to their attractive mechanical properties, superior wear, and corrosion resistance. In this study, the tribo-corrosion behavior of an equiatomic MoNbTaTiZr high entropy alloy consisting of all biocompatible elements was evaluated and compared with 304 stainless steel as a benchmark. The high entropy alloy showed a low wear rate and a friction coefficient as well as quick and stable passivation in simulated body fluid. An increase from room temperature to body temperature showed excellent temperature assisted passivity and nobler surface layer of the high entropy alloy, resulting in four times better wear resistance compared to stainless steel. Stem cells and osteoblast cells displayed proliferation and migratory behavior, indicating in vitro biocompatibility. Several filopodia extensions on the cell periphery indicated early osteogenic commitment, and cell adhesion on the high entropy alloy. These results pave the way for utilizing the unique combination of tribo-corrosion resistance, excellent mechanical properties, and biocompatibility of MoNbTaTiZr high entropy alloy to develop bioimplants with improved service life and lower risk of implant induced cytotoxicity in the host body.

Salt Preform Texturing of Absorbable Zn Substrates for Bone-implant Applications.

Surface roughness is an important factor in improving the bone-implant contact area to enhance bone regeneration, yet this aspect has not been applied to absorbable metals. Textured zinc surfaces with varying degrees of surface roughness were produced using a salt-preform method with fine- and coarse-grained salts and compared to a polished control sample. The resulting surfaces were characterized by scanning electron microscopy (SEM), surface roughness, corrosion rates, and in vitro cytotoxicity. The resulting textured surfaces exhibit micron-sized cavities and increased roughness consistent with the initial salt particle size. The corrosion rate was shown to accelerate significantly as compared to the polished control sample, and pre-osteoblasts displayed healthy morphologies on the textures. The results confirm textured zinc surfaces support cell adhesion and can be used to control the corrosion rate. This study represents an important intermediate step that can be applied to porous absorbable metal scaffolds for bone-implant applications.

Biofunctionalization of metallic implants by calcium phosphate coatings.

Metallic materials have been extensively applied in clinical practice due to their unique mechanical properties and durability. Recent years have witnessed broad interests and advances on surface functionalization of metallic implants for high-performance biofunctions. Calcium phosphates (CaPs) are the major inorganic component of bone tissues, and thus owning inherent biocompatibility and osseointegration properties. As such, they have been widely used in clinical orthopedics and dentistry. The new emergence of surface functionalization on metallic implants with CaP coatings shows promise for a combination of mechanical properties from metals and various biofunctions from CaPs. This review provides a brief summary of state-of-art of surface biofunctionalization on implantable metals by CaP coatings. We first glance over different types of CaPs with their coating methods and in vitro and in vivo performances, and then give insight into the representative biofunctions, i.e. osteointegration, corrosion resistance and biodegradation control, and antibacterial property, provided by CaP coatings for metallic implant materials.

Mechanical Strength, Biodegradation, and in Vitro and in Vivo Biocompatibility of Zn Biomaterials.

Zn-based biomaterials have emerged as promising new types of bioresorbable metallics applicable to orthopedic devices, cardiovascular stents, and other medical applications recently. Compared to other degradable metallic biomaterials (i.e., Mg- or Fe-based), Zn biomaterials have a more appropriate corrosion rate without hydrogen gas evolution. Here, we evaluated the potential of Zn-based metallics as medical implants, both in vitro and in vivo, alongside a standard benchmark Mg alloy, AZ31. The mechanical properties of the pure Zn were not strong enough but were significantly enhanced (microhardness > 70 kg/mm2, strength > 220 MPa, elongation > 15%) after alloying with Sr or Mg (1.5 at. %), surpassing the minimal design criteria for load-bearing device applications. The corrosion rate of Zn-based biomaterials was about 0.4 mm/year, significantly slower than that of AZ31. The measured cell viability and proliferation of three different human primary cells fared better for Zn-based biomaterials than AZ31 using both direct and indirect culture methods. Platelet adhesion and activation on Zn-based materials were minimal, significantly less than on AZ31. The hemolysis ratio of red cells (<0.5%) after incubation with Zn-based materials was also well below the ISO standard of 5%. Moreover, Zn-based biomaterials promoted stem cell differentiation to induce the extracellular matrix mineralization process. In addition, in vivo animal testing using subcutaneous, bone, and vascular implantations revealed that the acute toxicity and immune response of Zn-based biomaterials were minimal/moderate, comparable to that of AZ31. No extensive cell death and foreign body reactions were observed. Taken together, Zn-based biomaterials may have a great potential as promising candidates for medical implants.

Zinc-Based Biomaterials for Regeneration and Therapy.

Zinc has been described as the 'calcium of the twenty-first century'. Zinc-based degradable biomaterials have recently emerged thanks to their intrinsic physiological relevance, biocompatibility, biodegradability, and pro-regeneration properties. Zinc-based biomaterials mainly include: metallic zinc alloys, zinc ceramic nanomaterials, and zinc metal-organic frameworks (MOFs). Metallic zinc implants degrade at a desirable rate, matching the healing pace of local tissues, and stimulating remodeling and formation of new tissues. Zinc ceramic nanomaterials are also beneficial for tissue engineering and therapy thanks to their nanostructures and antibacterial properties. MOFs have large surface areas and are easily functionalized, making them ideal for drug delivery and cancer therapy. This review highlights recent developments in zinc-based biomaterials, discusses obstacles to overcome, and pinpoints directions for future research.

Blood-Brain Barrier Integrity and Clearance of Amyloid-ß from the BBB.

Alzheimer's disease, a type of dementia, affects memory, behavior, and cognitive processes in affected individuals. It is one of the prominent diseases, accounting for 60-80% of dementia cases and affecting a significant population of persons over the age of 65 years. While rare, Alzheimer's disease (AD) may affect the younger population as well. With such a widespread number of persons affected with AD, scientists have undertaken the initiative to develop a cure for this devastating disease; however, it has been deemed quite challenging. A dysfunctional blood-brain barrier, with impaired ability to clear amyloid-ß from the brain, has been directly linked to the development of Alzheimer's disease. The blood-brain barrier restricts the flow of many substances into and out of the brain and serves as a selective and protective barrier to the brain. A proper functioning blood-brain barrier contributes to the maintenance and integrity of the brain. In turn, different systems and mechanisms within the blood-brain barrier are set in place to facilitate mediated passage of materials and substances between the brain and the bloodstream. In relation to AD, the mediation of amyloid-ß clearance is of great importance in maintaining the blood-brain barrier's integrity.