Next Generation Biomaterials: On-Demand Oral Presentations
Sponsored by: ACerS Bioceramics Division, TMS Biomaterials Committee
Program Organizers: Roger Narayan, University of North Carolina; Min Wang, University of Hong Kong; Shawn Allan, Lithoz America LLC

Friday 8:00 AM
October 22, 2021
Room: On-Demand Room 3
Location: MS&T On Demand


Invited
Additive Manufacturing of Microstructured and Nanostructured Active Medical Devices: Roger Narayan1; 1University of North Carolina
    3Two photon polymerization is 3D printing technique that relies on the use of ultrashort laser pulses to polymerize and solidify photosensitive materials. The quadratic nature of the two photon absorption probability and the well-defined polymerization threshold of this technique allow one to overcome the diffraction limit and obtain structures containing features below one micrometer. Two photon polymerization has been to prepare medical devices out of biocompatible inorganic-organic hybrid materials and polymers. The use of biocompatible photoinitiators (e.g., a combination of riboflavin and triethanolamine) for two photon polymerization will be considered. Integration of electrochemical sensors with two photon polymerization-manufactured devices will be considered. Evaluation of two photon polymerization-manufactured materials using in vitro biological studies will be discussed. In addition, application-specific analysis of two photon polymerization-manufactured devices for biosensing and drug delivery will be discussed.

Invited
Hybrid Nanomanufacturing for Wearable Intelligence: Wenzhuo Wu1; 1Purdue University
    The seamless and adaptive interactions between functional devices and environment (e.g., the human body) are critical for advancing emerging technologies, e.g., wearable devices, consumer electronics, and human-machine interface. The state-of-the-art technologies require a complex integration of heterogeneous components to interface the ubiquitous and abundant environmental mechanical stimulus. Moreover, all existing technologies require a power source, which complicates the system design and limits operation schemes. I will discuss our recent progress in developing self-powered human-integrated nanodevices through the hybrid nanomanufacturing (e.g., 3D printing of self-assembled function materials) of heterostructured nanodevices with hierarchical architectures. This new class of wearable devices are conformable to human skins and can sustainably perform non-invasive functions, e.g., physiological monitoring and gesture recognition, by harvesting the operation power from the human body. This research is expected to have a positive impact and immediate relevance to many societally pervasive areas, e.g., biomedical monitoring, consumer electronics, and intelligent robotics.

Invited
Calcium Silicate & Calcium Aluminate Bioactive Cements: Carolyn Primus1; 1Primus Consulting
    Inert ceramics have been used for medical devices for centuries to replace hard tissue defects, especially in teeth. In the 1990s, calcium silicate cements, and later, the calcium aluminate cements, were found to be bioactive and biomineralizing, that is they form hydroxyapatite in vivo. This bioactivity has lead to improved outcomes for dental disease that were formerly expected to progress to tooth loss. Hydraulic calcium silicate and calcium aluminate cements are combined with radiopaque ceramic powder, which set with water and with body fluids. These cements perform differently than bioactive glasses which are resorbed. These cements are a boon to dental procedures where the pulp or dentin to arrest disease and support healing of the tissues. This presentation will describe the characteristics of, the indications for, and the various commercial products used for pediatric and adult dentistry to reduce tooth extraction.

Invited
Bijels-derived Structures for Tissue Engineering Applications: Min Wang1; 1University of Hong Kong
    Bicontinuous interfacially jammed emulsion gels (“bijels”) are a new class of soft matter containing two interpenetrating continuous phases. Owing to their unique bicontinuous structures, bijels and bijels-derived structures are very attractive for applications in many and diverse areas, including tissue engineering which solves difficult problems in human tissue repair. In tissue engineering, growth factors (GFs) delivered locally promote tissue regeneration. Furthermore, the unique bijels-derived structures may be employed as new vehicles for the controlled release of cells, including mesenchymal stem cells (MSCs), for tissue regeneration. We have developed a new technique for fabricating bijels and processes for producing bijels-derived structures for biomedical applications. New bijels-derived polymer-hydrogel hybrid structures exhibit good biocompatibility and biodegradability. The release of cells encapsulated in hybrid structures can be regulated by varying the crosslinking degree of the hydrogel. Released cells display good cell proliferation and cytoskeleton development. Also, locally delivered GF enhances cell proliferation and differentiation.

Invited
Novel Colloidal Based Biomaterials for Investigating Cellular Mechanotransduction Mechanisms: Ashley Brown1; 1North Carolina State University and UNC Chapel Hill
    Cells maintain homeostasis through monitoring the mechanics of their microenvironment. To understand these phenomena, hydrogel materials have been developed with either controllable linear elastic or viscoelastic properties. Biological tissues and biomaterials used for medical purposes often have complex mechanical properties. However, due to the difficulty in decoupling the elastic and viscous components of hydrogel materials, the effect of complex composite materials on cellular responses has largely gone unreported. Here, we describe a novel composite hydrogel system capable of decoupling and individually controlling both the bulk stiffness and surface viscoelasticity of the material by combining polyacrylamide gels with microgel thin films. By taking advantage of the high degree of control over stiffness offered by polyacrylamide gels and viscoelasticity of microgel thin films, it is possible to study the influence that bulk substrate stiffness and surface loss tangent have on complex fibroblast responses, including cellular and nuclear morphology and gene expression.

Invited
Calcium Phosphate Nanoparticles as Intrinsic Inorganic Antimicrobials: Vuk Uskokovic1; 1University of California
    Pathogenic and opportunistic bacteria rapidly develop resistance to antibiotics and it is likely that the next pandemic after COVID-19 will be bacterial. Inorganic nanoparticles offer one, albeit insufficiently explored, avenue for developing alternatives to the shortcomings of traditional, small-molecule antibiotics. Calcium phosphate (CP) nanoparticles belong to the new wave of abundant and naturally accessible nanomaterials applicable as a means to various technological ends. Here I will present findings of a comprehensive study on the intrinsic antibacterial effect exhibited by two distinct CP phases: an amorphous CP (ACP) and hydroxyapatite (HAp). In addition to these efficacy studies, results of studies aimed at elucidating the mechanism of action of CP nanoparticles will be presented. These findings present grounds for the optimization of CP nanoparticle properties for activity against regular and resistant bacterial strains comparable to that of Ag.

Invited
3D Binderjet Printing of Zirconia Based Ceramics, Innovative Processing Aspects and Challenges: Srimanta Barui1; Deepa Mishra1; Gowtham N H1; Bikramjit Basu1; 1Indian Institute of Science Bangalore
    Since the last two decades, additive manufacturing (AM) has transformed the landscape of engineering manufacturing towards the delivery of ‘on demand’ structural complexity with a minimal compromise in the end properties. Binderjet printing is one of the most promising AM techniques in ‘regenerative engineering’ to fabricate biomedical prosthesis and scaffolds with the host tissue mimicking properties. In this talk, the scope of the 3D binderjetting of zirconia based bioceramics will be discussed along with the long persisting challenges. ‘Printability’ of powder, flowability, cohesive bed packing are few examples of such challenging aspects. Additionally, some of the commercial binderjet printers print the layers in a ‘default core-shell’ manner which is detrimental in load bearing orthopedic applications. This talk will address the limitations for the first time in the literature, along with a spectrum of strategic troubleshooting methodologies to achieve complex zirconia-based architectures having consistent microstructure and biomedically relevant strength properties.

Invited
Sustained Delivery of Anticancer and Antimicrobial Drugs through Hollow Silica Capsules as Transporters: Eva Krakor1; Isabel Gessner1; Sanjay Mathur1; 1University of Cologne
    Hollow mesoporous silica particles (HMSC) have aroused tremendous interest in the field of drug delivery due to their unique properties like high biocompatibility, large surface areas and high loading capacities due to a protected hollow core. HMSC were synthesized using an iron oxide template which was coated with silica through sol-gel synthesis followed by the removal through acidic leaching. The porosity was analyzed using nitrogen adsorption-desorption method revealing a pore size of circa 4 nm. Cytotoxicity was determined using cell viability test towards HEK293 cells, demonstrating that no reduction of cell viability was observed even at high concentrations (100 µg/ml). Their capability as drug delivery vehicle was tested, by loading a hydrophilic antibiotic and a hydrophobic anticancer compound and a pH dependent release at was monitored via UV-Vis spectroscopy. Antibiotic-loaded HMSC also revealed a complete growth inhibition of E.coli over 18 hours, demonstrating their promising potential as drug delivery vehicle.

Invited
Combating Plastic Waste Accumulation through Innovative Biodegradable Superabsorbent Polymers Used in Disposable Consumer Products: Jeffrey Bates1; 1University of Utah
    Plastics are used every day, and are accumulating in landfills, soil, and water, and contribute to pollution. Companies have begun to focus on a circular economy, where the products they manufacture are recycled and feed back into the raw material chain for reuse in other products. While this strategy has its usefulness, it is limited in acknowledging that recycling facilities are not always available, consumer compliance is limited and subjective, and not all products are can be recycled because of the nature of their use. Here, we focus on superabsorbent polymers used in single-use consumer products where we improve the end-of-life environmental burden of products that degrade under non-specialized, environmental conditions within six months and do not create unstable intermediate molecules, including free radicals, but create nutrients for microorganisms. We report on our synthesis and characterization of SAPs as they meet the needs of the consumer and their end-of-life degradation.

Invited
Light-based Nanomedicine: Multimodal Diagnostics Combined with Drug-free Therapeutics: Tanveer Tabish1; Mohammed Sharahili2; 1Imperial College London; 2University of Exeter
    The ability of engineered nanoparticles that act as a multifunctional platform for target-specific detection and killing of cancer cell is of great interest in the field of nanomedicine. This talk will provide an overview of our recent developments on the design of gold nanostructures and nanographene to interface with cells for cancer diagnosis and treatment in a safe and targeted procedure using coherent anti-Stokes Raman scattering (CARS) microscopy. This presentation will also describe how variations in the size and shape of nanoparticles may provide fast and label-free detection combined with photodynamic therapy for cancer, enabling first-in-field multimodal imaging options and drug-free therapeutics. CARS microscopy coupled with nanotechnology has the potential to detect the diseased cells and kill them in these same clinical session in a safe and targeted fashion and can pave the way for rapid and highly efficient label-free diagnosis and continuous monitoring of cancer.

Invited
Addition of Antimicrobial Property to Hydroxyapatite/Collagen Bone-like Nanocomposite Utilizing Silver Nanoparticles: Masanori Kikuchi1; 1National Institute for Materials Science
    Hydroxyapatite/collagen bone-like nanocomposite, HAp/Col, is a bone void filler which is substituted with new bone by bone remodeling process. To ignore implant associated infection, antimicrobial activity for first 5 days is important to reduce the risk of infection. In the present study, we focus on silver nanoparticles (SNPs) as antimicrobial agent to prepare the HAp/Col having wide-spectrum antimicrobial activity and lower risk to form drug resistant microorganisms. Silver nanoparticles adsorbed on the HAp/Col powder (HCP) up to 1492 mg/gHCP in 48 h at SNP concentration of 143 g/gHCP and desorbed approximately 6 % of adsorbed SNPs in 1 days. According to antibacterial tests for Escherichia coli and Staphylococcus aureus, the adsorbed and desorbed amounts were sufficient. Further, cytotoxicity dosage of the present SNPs was higher than lowest efficient antibacterial amounts. These results demonstrated that the SNP-loaded HAp/Col is a good candidate for an antibacterial bone void filler material.

Invited
Stereolithographic Additive Manufacturing of Dental Crowns with Functionally Distributed Translucencies: Soshu Kirihara1; 1Osaka University
    In stereolithographic additive manufacturing, cross sectional patterns were created through photo polymerization by ultraviolet laser drawing on spread resin paste including ceramic nanoparticles, and solid models were sterically printed by layer lamination with chemical bonding. Through the smart additive manufacture, design and evaluation, bioceramic implants of dental crowns were fabricated successfully. Zirconia nanoparticles with different yttria contents were selected and dispersed into photo sensitive liquid resins from 40 to 60 % in volume fraction. The paste was spread on a glass substrate at 10 μm in layer thickness. An ultraviolet laser beam of 355 nm in wavelength was adjusted from 10 to 300 μm in variable diameter and scanned on the pasted resin surface. Irradiation power was changed automatically from 10 to 200 mW. The created precursor was dewaxed and sintered in an air atmosphere to obtain full ceramic components.


Effects of Thermal Stress on Calcium Phosphate Glass-derived Cements for Vital Pulp Therapy: Jerry Howard1; Jenna Young1; John Colombo2; Steven Naleway1; Krista Carlson1; 1University of Utah; 2University of Nevada, Las Vegas
    When the pulp of a tooth becomes infected or damaged, a root canal is often performed. When the pulp of a damaged tooth is healthy, however, a dentist may attempt to prevent a root canal by sealing the pulp with a cement in a technique called pulp capping. Previously, a bioactive cement composed of two glass compositions – sodium metasilicate and calcium phosphate – was developed. The setting time, sealing ability, and in-vitro phase maturation of the cement were shown to be favorable. To investigate the effects of particle morphology, a flame-spheroidization technique has been used to convert the calcium phosphate particles into microspheres. During spheroidization, differential cooling at the surface of the particles leads to a compressive stress layer, expected to affect the corrosion rate of the particles. As particle corrosion drives setting, the effects of thermal stresses on microsphere hardness, corrosion properties, setting time, and biocompatibility were investigated.


Alginate Core Polyurethane Shape Memory Foam Composite with Antimicrobial Properties for Negative Pressure Wound Therapy: Emily Lazarus1; Iris V. Rivero1; Robert Osgood1; 1Rochester Institute of Technology
    Negative Pressure Wound Therapy (NPWT), a clinical practice for treating wounds, fills the wound with foam and creates negative pressure removing exudate, increasing blood flow, and accelerating healing. Challenges include local antibiotic administration, frequent wound dressing changes, and standard sized foam. Shape memory polymer (SMP) foams have attracted attention due to their biocompatibility, shape memory effect, and volume filling capabilities. The conforming capabilities of SMP foams allows exact morphological compliance with the wound, increasing exudate uptake. We introduce a polyurethane SMP foam composite as the wound filler for NPWT with a zinc oxide coated alginate core to increase foam swelling and introduce antimicrobial properties. SMP foam composites were fabricated and characterized for fluid uptake, swelling, and shape recovery. Bactericidal characterization was performed to analyze the zinc oxide alginate core against Staphilococcus aureus and Pseudomonas aeruginosa. SMP foam composites prove to be an effective NPWT wound filler compared to traditional foam.


Additive Manufacturing of PLA-based Composites Using a Colloidal Feedstock: Biodegradable and Permanent Scaffolds in Medical Applications: Begońa Ferrari1; Ana Ferrandez-Montero1; Alvaro Eguiluz1; Antonio Javier Sanchez-Herencia1; 1Instituto de Cerámica y Vidrio, CSIC
     Thermal extrusion of materials, commonly known fused filament forming (FFF), is one of the most extended additive manufacturing technique, since it is easy to settle, safe, and inexpensive. The use of FFF to fabricate composite scaffolds require of a filament composed by the metal/ceramic load and a thermoplastic polymer as PLA, acting as structurers of the final shape and printing vehicle, being the dispersion of the metal/ceramic phase in the polymer matrix a key process condition to provide the biofunctionality. A colloidal approach will be described to process of PLA-based filaments with different compositions, ranging 5-50 vol.% of well dispersed Mg or HA. Powders were stabilized to be compatible with the PLA matrix during printing, using a 3D desktop printer. Dispersion allows including enough inorganic load in the filament to shape a 100% inorganic implant after the ad hoc thermal treatment. Cellular adhesion and proliferation tests evidence bioactivity and biocompatibility


Enzymes Immobilized on Nanocarriers for the Degradation of Synthetic Polymers: Eva Krakor1; Sanjay Mathur1; Isabel Gessner1; Michael Wilhelm1; 1University of Cologne
    Sustainable concepts for the degradation of omnipresent industrial plastics are a pressing environmental and societal need. Therefore enzymes (lipase and cutinase) were covalently immobilized on carrier nanoparticles (SiO2 and Fe3O4@SiO2) through 3-(aminopropyl)trimethoxysilane (APTMS) linkers that provided terminal amino groups for forming a stable bond to enzyme molecules upon addition of glutaraldehyde. The presence of enzymes on the surface was confirmed by zeta potential and XPS measurements, while their degradation activity and long-term stability over a time-period of 144 hours was demonstrated by monitoring the conversion of 4-nitrophenyl acetate (4-NPA) to 4-nitrophenol (4-NP) by UV-Vis spectroscopy. Additionally, enzymatic decomposition of PCL was verified through SEM and mass loss analyses of intermediate stages.


Impact of Wall Thickness and Pores Size Variation on Hydroxyapatite Based Triply Periodic Minimal Surfaces: Islam Bouakaz1; David Grossin2; Gregory Nolens1; 1CERHUM; 2Institut National Polytechnique de Toulouse
    Triply Periodic Minimal Surfaces(TPMS) are three dimensional mathematical structures that presents a continuous tortuosity which can help cell proliferation in bone substitutes. the mechanical properties of lattice structures are impacted by the properties of the material, relative density and structure of the lattice. In order to compare different structure types and to understand the effect of pores size and wall thickness change on the mechanical and biological properties, 3 different Hydroxyapatite based TPMS were printed using a Digital Light Processing 3D printer (VAT Photopolymerization). Pore sizes and wall thicknesses were varied for each TPMS. as the printed parts were thermally debinded and sintered, the compression tests were conducted according to the ISO 13175 standard for calcium phosphate porous bone substitutes. bending strength and Young's modulus were determined using a 3-point bending test. cell proliferation in the selected structure was tested using a dynamic in vitro tests.


4D Bioprinting for Making Hierarchical Composite Scaffolds for Blood Vessel Regeneration: Shangsi Chen1; Min Wang1; 1University of Hong Kong
    There is a great interest in 4D bioprinting of tissue engineering scaffolds for blood vessel regeneration. But the lack of high elasticity and inability to achieve hierarchical architectures mimicking blood vessels have hindered the progress. Furthermore, programmed shape morphing of scaffolds to form tubular structures as blood vessels is desired. In this study, highly elastic thermoplastic urethane (TPU) and shape-memory PDLLA-co-TMC were homogeneously blended and then 3D printed for making composite scaffolds. Subsequently, a layer of electrospun PLGA/GelMA@PDA fibers was deposited on PDLLA-co-TMC/TPU scaffolds, with hFGF growth factor being loaded in PDA spheres. Finally, another layer of GelMA/Gel bioinks encapsulated with BMSC and HUVEC cells was printed on scaffolds. The maximum elongation of composite scaffolds was over 600%, which is highly desirable. Scaffolds could self-fold into tubular shape at body temperature. hFGF could be sustainably released in different pH conditions. The complex scaffolds also provided high cell viability and proliferation.


Light-adaptive Dynamic DNA-based Hydrogel: Joonas Ryssy1; Sesha Manuguri1; Anton Kuzyk1; 1Aalto University
    Living organisms are abundant with examples of light adaptable features that are crucial for their survival. Cuttlefish, for example, can detect the amount of light in the surrounding and can adapt their pigments to match this. As technology is hurdling towards bio-inspired and bio-compatible solutions, inherent adaptability to external stimulus remains an elusive quality. Here, a concept is introduced that incorporates light adaptive features for programmable material responses. By combining programmable DNA strands with gold nanorods, we propose a strategy to engineer dynamic light adaptive features into hydrogel materials. The strategy utilizes fabricating a poly(acrylamide-co-DNA-AuNR) hydrogel system consisting of thermo-reversible hydrogen bonds, with light adaptive reconfigurable mechanical and optical features. Upon visible light stimulus, the photothermal energy induced by the AuNRs by converting light to heat, thereby leading to macroscopic reconfiguration of mechanical and endowing hydrogels with polarizable optical properties.