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Infections associated with antibiotic-resistant bacteria have become a threat to the global public health. Antimicrobial polymers, which are synthetic mimics of antimicrobial peptides, have gained increasing attention, as they may have a lower chance of inducing resistance. The cationic-hydrophobic balance and distribution of cationic and hydrophobic moieties of these polymers is known to have a major effect on antimicrobial activity. We studied the properties of a series of facially amphiphilic antimicrobial surfactant-like poly(ester urethane)s with different hydrophobic pendant groups (P1, P2, and P3) and cationic groups distributed uniformly along the polymer chain. These polymers exhibited bactericidal activity against Gram-negative Escherichia coli and Pseudomonas aeruginosa, as well as Gram-positive Staphylococcus aureus and Staphylococcus epidermidis. Microscopy and dye release assays demonstrated that these polymers cause membrane disruption, which is dependent on the cationic-hydrophobic ratio in the polymer. Membrane permeability assays revealed that these polymers can permeabilize the outer membrane of E. coli and damage the cytoplasmic membrane of both E. coli and S. aureus. In addition, our results indicate that the three polymers exhibit a different extent of membrane disruption against E. coli. P1 caused minor damage to the cytoplasmic membrane integrity, but it was able to dissipate the cytoplasmic membrane potential, leading to cell death. P2 and P3 depolarized the cytoplasmic membrane and also caused significant damage to the cytoplasmic membrane. Overall, we showed a new class of broad-spectrum bactericidal polymers whose membrane disrupting ability against E. coli correlates with the structural differences of the hydrophobic pendant groups.

The increasing incidence of drug-resistant strains of bacteria necessitates the development of new classes of antimicrobials. Host defense peptides, also known as antimicrobial peptides, are promising in this regard but have several drawbacks. Herein, we show that peptidomimetic polyurethanes with pendant functional groups that mimic lysine and valine amino acid residues have high antibacterial activity against Gram negative

Mg alloys offer potential advantages over conventional biomedical implant materials because of their biodegradability and biocompatibility, but could be limited by their poor mechanical properties. In this study, laser shock peening (LSP), a surface processing technique, was applied to improve the mechanical properties of the AZ31B magnesium (Mg) alloy. It was demonstrated that LSP increased the hardness and yield strength of the Mg alloy. Due to the hardening, LSP significantly improved the wear resistance and fatigue performance of the Mg alloy. In addition, immersion tests carried out in cell culture medium revealed that LSP did not significantly increase Mg2+ release and weight loss. Furthermore, an in vitro cell culture study showed that the LSP-treated samples have cell-compatibility comparable to untreated samples. Thus, the LSP technique could, with further study, advance the clinical utility of Mg alloys in the orthopedic field.

Presented here is a novel method for encapsulating proteins into biodegradable, thermoresponsive coacervate-type polyesters. Bovine serum albumin (BSA) was efficiently incorporated into coacervate droplets via a simple thermoresponsive encapsulation mechanism. Tunable modular systems for encapsulation such as the one presented here may be useful in a range of protein delivery applications.

The increasing incidence of drug-resistant strains of bacteria necessitates the development of new classes of antimicrobials. Host defense peptides, also known as antimicrobial peptides, are promising in this regard but have several drawbacks. Herein, we show that peptidomimetic polyurethanes with pendant functional groups that mimic lysine and valine amino acid residues have high antibacterial activity against Gram negative Escherichia coli, yet are less effective against Gram positive Staphylococcus aureus. All the polyurethanes designed in this study display high bactericidal activity against E. coli, whereas the polyurethanes with high concentrations of lysine mimicking functional groups display minimal cytotoxicity toward mammalian cells. Control experiments with pexiganan, an analogue of the host defense peptide magainin, showed that the polyurethanes described here have high bactericidal activity, while having comparable hemocompatibility and lower mammalian cell toxicity. Overall, the results poin...

Following the success of silicate-based glasses as bioactive materials, silicates are believed to play important roles in promoting bone formation and have therefore been considered to provide a hydroxyapatite (HAP) surface layer capable of binding to bone as well as potentially being a pro-osteoinductive factor. Natural silicate minerals and silicate-substituted HAPs are also being actively investigated as orthopaedic bone and dental biomaterials for application in tissue engineering. However, the mechanisms for the proposed roles of silicate in these materials have not been fully understood and are controversial. Here, we review the potential roles of silicate for bone tissue engineering applications and recent breakthroughs in identifying the cellular-level molecular mechanisms for the osteoinductivity of silica. The goal of this article is to inspire new ideas for the rational design of third-generation cell-and gene-affecting biomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2090-2102, 2017.

The rapid increase in bacterial infections and antimicrobial resistance is a growing public health concern. Infections arising from bacterial contamination of surgical tools, medical implants, catheters, and hospital surfaces can potentially be addressed by antimicrobial polymeric coatings. The challenge in developing such polymers for in vivo use is the ability to achieve high antimicrobial efficacy while at the same time being nontoxic to human cells. Although several classes of antimicrobial polymers have been developed, many of them cannot be used in the clinical setting due to their nonselective toxicity toward bacteria and mammalian cells. Here, we demonstrate that coumarin polyesters with cationic pendant groups are very effective against Gram negative Pseudomonas aeruginosa. Coumarin polyesters with pendant cationic amine groups were coated onto glass coverslips and tested for their antimicrobial activity against P. aeruginosa colonization of the surface. The results demonstrate that the cationic coumarin polyester kills the surface attached bacterial cells preventing biofilm formation but does not show any hemolytic activity or discernible toxicity toward mammalian cells. The antimicrobial polyesters described in this work have several advantages desired in antimicrobial coatings such as high antimicrobial activity, low toxicity toward mammalian cells, visualization and ease of synthesis and fabrication, all of which are necessary for translation to the clinic.

The emergence of microbial resistance to several antimicrobials of last resort is causing a global crisis and presents a scenario where hospitals will be unable to address healthcare issues that become complicated due to drug-resistant bacteria. Natural or synthetic antimicrobials are the standard of care for addressing bacterial infections. However, due to the rapid emergence of resistance to these classes of antimicrobials, alternative platforms such as antimicrobial polymers are being evaluated as viable options. In this regard, synthetic cationic water-soluble polymers are an emerging class of antimicrobials that deserve a closer look. Over the decades, several classes of antimicrobial polymers have been explored and have been demonstrated to have good antimicrobial activity, which is normally due to the cationic nature of the polymers. The challenge in such cationic polymers is to maximize their bacterial activity while minimizing the collateral damage to mammalian cells. In this chapter, various classes of synthetic cationic water-soluble antimicrobial polymers are described, spanning both older versions such as polyhexanide and newer cationic polyurethanes.

Accumulating evidence over the last 40 years suggests that silicate from dietary as well as silicate-containing biomaterials is beneficial to bone formation. However, the exact biological role(s) of silicate on bone cells are still unclear and controversial. Here, we report that orthosilicic acid (Si(OH)4) stimulated human mesenchymal stem cells (hMSCs) osteoblastic differentiation in vitro. To elucidate the possible molecular mechanisms, differential microRNA microarray analysis was used to show that Si(OH)4 significantly up-regulated microRNA-146a (miR-146a) expression during hMSC osteogenic differentiation. Si(OH)4 induced miR-146a expression profiling was further validated by quantitative RT-PCR (qRT-PCR), which indicated miR-146a was up-regulated during the late stages of hMSC osteogenic differentiation. Inhibition of miR-146a function by anti-miR-146a suppressed osteogenic differentiation of MC3T3 pre-osteoblasts, whereas Si(OH)4 treatment promoted osteoblast-specific genes transcription, alkaline phosphatase (ALP) production, and mineralization. Furthermore, luciferase reporter assay, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence showed that Si(OH)4 decreased TNFα-induced activation of NF-κB, a signal transduction pathway that inhibits osteoblastic bone formation, through the known miR-146a negative feedback loop. Our studies established a mechanism for Si(OH)4 to promote osteogenesis by antagonizing NF-κB activation via miR-146a, which might be interesting to guide the design of osteo-inductive biomaterials for treatments of bone defects in humans. Statement of Significance Accumulating evidence over 40 years suggests that silicate is beneficial to bone formation. However, the biological role(s) of silicate on bone cells are still unclear and controversial. Here, we report that Si(OH)4, the simplest form of silicate, can stimulate human mesenchymal stem cells osteoblastic differentiation. We identified that miR-146a is the expression signature in bone cells treated with Si(OH)4. Further analysis of miR-146a in bone cells reveals that Si(OH)4 upregulates miR-146a to antagonize the activation of NF-κB. Si(OH)4 was also shown to deactivate the same NF-κB pathway to suppress osteoclast formation. Our findings are important to the development of third-generation cell-and gene affecting biomaterials, and suggest silicate and miR-146a can be used as pharmaceuticals for bone fracture prevention and therapy.

Recently, we reported a new class of biodegradable, thermoresponsive polyesters (TR-PEs) inspired by polyacrylamides and elastin-like peptides (ELPs). The polyesters exhibit tunable cloud point temperatures (Tcp) and thermoresponsive coacervation in aqueous solution as shown via UV-vis spectroscopy, 1H NMR, and DLS. However, the Tcp of all TR-PEs remained low (

Nickel-titanium (NiTi) alloy is an attractive material for biomedical implant applications. In this study, the effects of laser shock peening (LSP) on the biocompatibility, corrosion resistance, ion release rate and hardness of NiTi were characterized. The cell culture study indicated that the LSP-treated NiTi samples had lower cytotoxicity and higher cell survival rate than the untreated samples. Specifically, the cell survival rate increased from 88 ± 1.3% to 93 ± 1.1% due to LSP treatment. LSP treatment was shown to significantly decrease the initial Ni ion release rate compared with that of the untreated samples. Electrochemical tests indicated that LSP improved the corrosion resistance of the NiTi alloy in simulated body fluid, with a decrease in the corrosion current density from 1.41 ± 0.20 μA/cm2 to 0.67 ± 0.24 μA/cm2 . Immersion tests showed that calcium deposition was significantly enhanced by LSP. In addition, the hardness of NiTi alloy increased from 226 ± 3 HV before LSP to 261 ± 3 HV after LSP. These results demonstrated that LSP is a promising surface modification method that can be used to improve the mechanical properties, corrosion resistance and biocompatibility of NiTi alloy for biomedical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1854-1863, 2019.

Hierarchical structures on metallic implants can enhance the interaction between cells and implants and thus increase their biocompatibility. However, it is difficult to directly fabricate hierarchical structures on metallic implants. In this study, we used a simple one-step method, ultrasonic nanocrystal surface modification (UNSM), to fabricate hierarchical surface structures on a nickel-titanium (NiTi) alloy. During UNSM, a tungsten carbide ball hits metal surfaces at ultrasonic frequency. The overlapping of the ultrasonic strikes generates hierarchical structures with microscale grooves and embedded nanoscale wrinkles. Cell culture experiments showed that cells adhere better and grow more prolifically on the UNSM-treated samples. Compared with the untreated samples, the UNSM-treated samples have higher corrosion resistance. In addition, the surface hardness increased from 243 Hv to 296 Hv and the scratch hardness increased by 22%. Overall, the improved biocompatibility, higher corrosion resistance, and enhanced mechanical properties demonstrate that UNSM is a simple and effective method to process metallic implant materials.

Magnesium alloys have tremendous potential for biomedical applications due to their good biocompatibility, osteoconductivity, and degradability, but can be limited by their poor mechanical properties and fast corrosion in the physiological environment. In this study, ultrasonic nanocrystal surface modification (UNSM), a recently developed surface processing technique that utilizes ultrasonic impacts to induce plastic strain on metal surfaces, was applied to an AZ31B magnesium (Mg) alloy. The mechanical properties, corrosion resistance, and biocompatibility of the alloy after UNSM treatment were studied systematically. Significant improvement in hardness, yield stress and wear resistance was achieved after the UNSM treatment. In addition, the corrosion behavior of UNSM-treated AZ31B was not compromised compared with the untreated samples, as demonstrated by the weight loss and released element concentrations of Mg and Al after immersion in alpha-minimum essential medium (α-MEM) for 24h. The in vitro biocompatibility of the AZ31B Mg alloys toward adipose-derived stem cells (ADSCs) before and after UNSM processing was also evaluated using a cell culture study. Comparable cell attachments were achieved between the two groups. These studies showed that UNSM could significantly improve the mechanical properties of Mg alloys without compromising their corrosion rate and biocompatibility in vitro. These findings suggest that UNSM is a promising method to treat biodegradable Mg alloys for orthopaedic applications.

An innovative surface treatment method, ultrasonic nanocrystal surface deformation (UNSM), was used to process a magnesium (Mg) AZ31B alloy in this study. In the UNSM process, ultrasonic impacts induce plastic deformation on material surface that lead to grain refinement and surface morphology changes. The hardness, tensile strength, surface morphology and weight loss from immersion testing of the materials before and after UNSM were studied systematically. Compared with the unprocessed samples, the UNSM-processed samples show significant improvements in hardness (64%) and yield stress (43%). Surface topography results reveal that UNSM generates a smooth surface with an average roughness of 93 nm. In addition, the immersion results in cell medium demonstrate that the UNSM-processed group showed lower weight loss, especially during the early immersion period. It can thus be concluded that UNSM can significantly improve the hardness and yield strength of Mg alloys and reduce the corrosion rate, indicating that UNSM is a promising new method to enhance the mechanical properties of the degradable Mg alloys.

In this study, we investigated the mechanical properties of AZ31B Mg alloy before and after laser shock peening (LSP). The hardness of the AZ31B Mg alloy increased from 57 HV to 69 HV after LSP. The yield strength increased from 128 MPa to 152 MPa. Wear resistance was significantly improved after LSP. Immersion testing showed that LSP did not significantly increase the element release and weight loss in simulated body fluid. We have demonstrated that LSP is an effective way to improve the mechanical properties of the AZ31B Mg alloy.

The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure–reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, β-CaSiO3) and wollastonite (wol, α-CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X-ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were more osteoinductive for the former. Thus, we showed that crystal structure is a fundamental parameter to be considered in the intelligent design of pro-osteogenic, partially resorbable bioceramics.

Inspired by nature's toughening mechanisms, we designed a new polyhedral oligomeric silsesquioxane (POSS)-derived hybrid glass (PHG) that has covalent interactions on the molecular scale between the inorganic POSS cage and organic phase. These features allow “elastic deformation” of the inorganic POSS cage in limited scale. The final product is a bulk hybrid material with toughness (3.56 ± 0.25 MPa·m1/2) similar to natural bone (2.4–5.3 MPa·m1/2). PHG exhibited excellent bioactivity by promoting the formation of plate-like hydroxyapatite on its surface in simulated body fluid and showed good cell adhesion. PHG also can be a platform to guide adipose tissue-derived mesenchymal stem cells differentiation and mineralization. The key structural features of this material can be used to guide the design of bio-inspired composites with unique toughness, which would be of great benefit to hard tissue engineering.

The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure-reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, β-CaSiO3) and wollastonite (wol, α-CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X-ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were more osteoinductive for the former. Thus, we showed that crystal structure is a fundamental parameter to be considered in the intelligent design of pro-osteogenic, partially resorbable bioceramics.