4D Printing of Polymer Composites to Engineer Resorbable and Deployable Implants

Abstract

Medical implants include products that are used to replace or restore the function of any damaged organ or tissue inside the body. The current generation of implants are mostly made from non-degradable materials and are implanted via open surgeries. The patients often need to undergo multiple surgical interventions in case of implant failure or secondary complications. This inevitably leads to increased pain, hospitalization times, and higher costs. Resorbable medical implants offer potential advantages, as they completely degrade inside the body into non-toxic byproducts in a timely fashion, thereby avoiding multiple revision procedures. A few examples exist of resorbable implants used in clinics, such as polymeric bone fixation devices. On the other hand, deployable implants provide the feature of implantation via minimally invasive procedures. Typical examples of such implants include Nitinol-based stents, which are non-degradable and require surgical procedures for initial implantation. However, combining both features, including absorbability and deployability, in a single implant is scarce. A typical way of achieving this is to use an absorbable smart material that can be triggered using benign stimulation methods to deploy at the site minimally invasively. The thesis encompasses engineering such absorbable and stimuli-responsive polymer composites fabricated into customized designs of potential implants using design- aided additive manufacturing. The first part of the thesis aims at design optimization, using an absorbable shape memory polymer (SMP) that can exhibit shape recovery at physiological temperatures. Using anisotropic design principles, the SMP was programmed to generate out- of-plane shape deformations in as-printed planar structures, such as hollow tubes with cells in the lumen. The later parts of the thesis deal with engineering the shape memory polymer with functional nanoparticles that are responsive to non-contact stimuli, such as alternating magnetic field, or near-infrared (NIR) for remotely deployable medical implants. Lastly, as a proof-of- concept, a biliary stent is fabricated using absorbable polymer and later endowed with NIR- responsiveness and imaging potential for potential image-guided deployment.

Chapter 1 presents a comprehensive literature survey on resorbable and deployable medical implants, focusing on the materials and manufacturing employed. The need for resorbable polymers, additive manufacturing (3D printing and 4D printing) as potential manufacturing techniques, the role of design and smart materials on shape change, and different stimulation methods to trigger shape change are outlined. A brief overview of the potential biomedical applications is also presented, emphasizing biliary stents and deployable bone tissue scaffolds prepared by such materials. In Chapter 2, details of experimental methods and characterization techniques employed to carry out the work in this thesis are mentioned. Chapter 3 presents a dual shape-morphing strategy comprising design-aided additive manufacturing and shape memory properties of polymers to fabricate complex shapes, such as cellularized hollow tubes. FEA simulations are used to predict the different types of shape deformations, such as out-of-plane bending and twisting in the as-printed structures by varying infill angles during printing. Hollow tubes of varying lengths and diameters can be obtained by quantitative predictions from the simulations. The obtained tubes can then be cellularized by utilizing the shape memory property of the polymer, resulting in cellularized vascular grafts for improved patency. Chapter 4 utilizes an alternating magnetic field as a stimulation for fabricating deployable tissue scaffolds. The shape memory polymer was reinforced with magnetic nanoparticles to realize remote heating under an alternating magnetic field and at physiological temperatures. The as-printed magnetic scaffolds could be deployed minimally invasively following shape recovery from deformed shapes into original shapes under magnetic heating. Furthermore, the composites exhibited in vitro osteogenesis, cytocompatibility, and in vivo compatibility. Thus, the 4D printed shape memory magnetic nanocomposite presented here could be an excellent candidate biomaterial for engineering deployable scaffolds and medical implants, among other implantable applications. In Chapter 5, near-infrared (NIR) light was used as a potential stimulation to realize in situ deployable tissue scaffolds. The shape memory polymer was nanoengineered with

photothermal nanofillers to fabricate composites by 3D printing. The composites demonstrated significantly higher osteogenic potential in vitro, as revealed by the significantly enhanced alkaline phosphatase (ALP) secretion and mineral deposition compared to the neat polymer. Intraoperative deployability and in vivo bone regeneration ability of the composites were demonstrated using self-fitting scaffolds in critical-sized cranial bone defects in rabbits. The composite scaffolds fabricated here offer an innovative strategy for minimally invasive deployment to fit irregular and complex tissue defects for bone tissue regeneration. In Chapter 6, bioresorbable biliary stents were fabricated as a different class of implants using 3D printing and elcectrospinning to obtain covered stents of custom lattice designs. The stents were tested for in vitro mechanical properties and degradation properties and their deployment was assessed in pre-clinical porcine model using the Seldinger technique. In Chapter 7, NIR-responsive composites were prepared using photothermal nanoparticles with imaging potential using fluorescent imaging and photoacoustic imaging techniques. In Chapter 8, the overall findings of the work are summarized, and a brief perspective on the scope of future work based on the findings of this thesis is also presented. Taken together, this thesis presents a combination of engineering materials, design optimization, smart use stimulation strategies, for the rationale development of bioresorbable and deployable implants.