Society for Biomaterials: Biological Response to Materials and Material’s Response to Biological Environments: Session I
Program Organizers: Thomas Dziubla, University of Kentucky; Christopher Siedlecki, Penn State College of Medicine; Jeffrey Capadona, Case Western Reserve University; Lynne Jones, Johns Hopkins Orthopaedics

Monday 8:00 AM
October 10, 2022
Room: 315
Location: David L. Lawrence Convention Center

Session Chair: Lynne Jones, Johns Hopkins University


8:00 AM Introductory Comments

8:05 AM  Invited
Biomaterial-induced Activation of the Blood Coagulation Cascade: Christopher Siedlecki1; Lichong Xu1; 1Penn State College of Medicine
    The blood coagulation cascade is a complex series of enzymatic reactions leading to the formation of a crosslinked fibrin mesh that is capable of trapping and activating blood platelets, leading to the formation of a thrombus. The intrinsic pathway of this system is activated by contact of the zymogen human Factor XII (also known as Hageman Factor) with a foreign surface such as an implanted biomaterial. It was long believed that the cascade was initiated by FXII contact with anionic surfaces, but more recent studies have shown that a multitude of different surfaces can activate the cascade. In this presentation, we will discuss the relationships between materials bearing a wide variety of surface properties and the subsequent activation of FXII, as well as how surface-activated FXII affects other pathways that lead to propagation of activation, amplification of activated FXII, and even self-inhibition of coagulation.

8:35 AM  
Effects of Phospholipid Saturation and Cholesterol Concentration on Liposome Interaction with Fungal and Mammalian Cells: Veronica Lamastro1; Kayla Campbell1; Peter Gonzalez1; Anita Shukla1; 1Brown University
    Liposomes are lipid-based nanoparticles used to treat fungal infections with the potential to decrease cytotoxicity of antifungal drugs. Optimal liposomal formulations would preferentially target fungal cells over mammalian cells. Here, we investigated the effect of lipid saturation and cholesterol concentrations (15 – 40 w/w%) in liposomes on liposome-fungal and liposome-mammalian cell interaction. Generally, a high level of Candida albicans-liposome interaction was observed (>80%). Liposome interaction was observed with 10 – 50% of endothelial and 10 – 40% of fibroblast cells for monounsaturated formulations at different cholesterol concentrations; liposomes fabricated with saturated and polyunsaturated lipids showed approximately 100% interaction with mammalian cells. Additionally, formulations using unsaturated lipids mimicking the clinically used antifungal liposome AmBisome, typically fabricated with saturated lipids, had decreased levels of interaction with mammalian cells while maintaining high levels of C. albicans interaction. Overall, this work demonstrates the importance of lipid saturation in liposome compositions when designing antifungal liposomes.

8:55 AM  
Targeting Cancer-associated Fibroblasts within a Tumor Microenvironment via Liposomes with Arginine-based Surface Modifiers: Tanzeel Ur Rehman1; Kaitlin Bratlie1; 1Iowa State University
    Fibroblasts are critical in wound healing as they synthesize extracellular matrix, collagen, and support the wound healing process by differentiating into myofibroblast phenotype. Myofibroblasts promote wound healing and wound closure; however, in the presence of cancer, myofibroblasts can act as cancer-associated fibroblasts (CAFs) enhancing tumor progression, metastasis and developing resistance to chemo- and radiotherapy drugs. Therefore, there is need to synthesize drug delivery vehicles that can actively target CAFs, while being more toxic towards CAFs compared to fibroblasts. Here, we used 17 arginine derivatives to modify the surface of doxorubicin-loaded DOPE: DOPC liposomes and examined the toxicity and cell internalization using both fibroblasts and activated myofibroblasts phenotype. Promising results suggested that these arginine-like molecules can be used to specifically target CAFs compared to fibroblasts with a higher toxicity and cell internalization. This work attests to the significance of investigating the interactions of modified and unmodified liposomes with fibroblasts and myofibroblasts.

9:15 AM  
Antibacterial Activity of Titanium-based Material Systems: Golnaz Karbalaei Saleh1; Parvane Shahmohammadi2; Milad Rasouli3; 1Karaj Islamic Azad University.; 2Razi University; 3Tehran University of Medical Sciences
    Titanium-based material systems are frequently employed in medical and dental applications due to their unique qualities such as outstanding mechanical capabilities, high corrosion resistance, and great biocompatibility. However, titanium biocompatibility is influenced by surface oxide layer features such as chemical composition, microstructure, and surface shape. The surface characteristics and compatibility of titanium implants can be improved by coating them with bioactive materials such as calcium phosphates. This study aimed to characterize a Zn/Mg enhanced calcium phosphate coating generated on a titanium surface with nanotubes using a two-step pulsed electrodeposition process. The influence of the coating deposition condition on the phase structure, as well as varying levels of Zn and Mg, on antibacterial activity and protein absorption, was investigated. Our findings revealed that synthesis factors, as well as the amount of Zn/Mg elements, influence the crystal size, shape, and distribution of calcium phosphate deposition.

9:35 AM  
Biological Response to Medical Implants: The Good, The Bad, and The Ugly: Lynne Jones1; 1Johns Hopkins Orthopaedics
     Medical implants are synthetic devices or tissues that are placed inside the body to support, reconstruct, or replace damaged or diseased biological structures. With technological advances, today’s implants can also deliver medications or serve as sensors to monitor body functions. The long-term survivorship of the implant is dependent on the design of the implant including the materials, the surgical technique, and the host. This presentation will focus on the biological response to materials – also called the host response. Biocompatibility is often discussed but frequently misunderstood. As described by Dr. James Anderson (Polymer Science: A Comprehensive Reference; 2012), biocompatibility is “the ability of a material to perform with an appropriate host response in a specific application.” However, host responses can range from bioinert to fibrous encapsulation to adverse responses (e.g., tissue lysis, pseudotumors, tumors). The reactions involved may engage similar cells. Therefore, it is important to appreciate the potential mechanisms involved in order to understand and predict biocompatibility as well as adverse events.

9:55 AM Break

10:15 AM  Invited
Bone Formation via Acoustic Radiation Force: Transdermal Stimulation of Hydrogel-encapsulated Stem Cells: Yusuf Khan1; Kevin Grassie2; Hanna Anderson2; William Linthicum2; Bryan Huey2; Fayekah Assanah2; 1University of Connecticut Health Center; 2University of Connecticut
    Tissue Engineering continues to be a viable strategy for healing large scale, complex injuries to both hard and soft tissue, with many approaches being added to the clinical armamentarium. Here we sought to combine both clinical and preclinical strategies into a solution for healing bony defects by combining hydrogel-based cell delivery with low intensity pulsed ultrasound, a clinically proven treatment for fractures, to permit the implantation of cell-laden hydrogels into large-scale bone defects followed by intermittent transdermal application of LIPUS-derived acoustic radiation force to the implanted cells. We have also developed in silico models that predict the mechanical forces applied to encapsulated cells and can serve as a design guide for our system. In vivo evaluation of our system has demonstrated full defect healing in large scale bone defects, suggesting that this system may be used for bony repair and with further refinement may have clinical utility.

10:45 AM  Invited
Wear Particle-induced Differentially Polarized Macrophages Exhibit Variation in Protein Profile than M1 and M2: Divya Bijukumar1; Vaishnavi Beena Valsan1; Ryan Bomgarden2; Guoxing Zheng1; Mark Barba3; Deborah Hall4; Mathew Thoppil Mathew1; Robin Pourzal4; 1University of Illinois; 2Thermofisher Scientific; 3Orthoilinois; 4Rush University Medical Centre
    Biological factors from the local microenvironment are the major driving factor for macrophage polarization. However, studies have demonstrated that nanoparticles can modulate macrophage polarization into different phenotypes. It was previously demonstrated that CoCrMo nanoparticle-induced macrophages (MCA) exhibit a difference in cytokine and chemokine expression than M1 and M2 macrophages, suggesting the possibility of a novel macrophage population. In this study, we performed mass spectroscopy to investigate the variation in macrophage phenotype induced by CoCrMo nano and microparticles and compare it with M1 and M2 macrophages. We hypothesize that, MCA macrophages polarized by CoCrMo particles will induce a distinct protein expression profile based on the particle size in comparison to M1 and M2 macrophages. The mass spectroscopy results support our hypothesis that MCA macrophages exhibit differential phenotypic characteristics based on the size of the particles. MCA-1 holds a unique position compared to other groups suggesting a significant variation in protein expression.