Next Generation Hydroxyapatite Bone Grafts: Copper-Inclusion and Photocurable Composites
Date
2023-12
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Publisher
New York State College of Ceramics at Alfred University. Inamori School of Engineering.
Abstract
Orthopedic infection is a massive threat whose prevalence and invasiveness increases in parallel to a rapidly aging population. The rise in antibiotic-resistance deepens this threat to a level where infection is projected to become a leading cause of death in the next two decades, thus substantiating the need for alternative therapies. A shift from treatment solutions towards prophylactic practices will likely pave the way for the next generation of bone grafts. Hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), the most widely used bone grafting materials clinically, do not have any inherent antimicrobial properties. Transition metals, such as Cu, are known to be antibacterial and have thus been incorporated into HA or β-TCP for that purpose, which is the motivation for the following work. Since ceramic particles are typically delivered as a grafting material in composite form, a wide range of HA- and β-TCP-polymer composites are reviewed extensively, including the various fabrication methods that have been developed recently. Clinically implemented composites are surveyed, with commercially available products and their respective uses highlighted.
Robust structural and chemical analysis of these types of materials is severely lacking, which limits our understanding of their antibacterial nature and leaving some conclusions to be drawn based upon conjecture. Our fundamental understanding of any antibacterial effect relies on the understanding of the tenancy of substituted ion(s) and its correlation to key physical, structural, and chemical properties. This gap in knowledge leaves room for a substantial body of work designed to explore Cu-inclusion in an HA lattice. Motivated by this, a series of Cu-containing HA (CuHA) was synthesized via aqueous co-precipitation. This work tracks changes in lattice parameters with increased Cu content, conducted through Pawley fits of X-ray powder diffraction (XRD) patterns. High-temperature in situ XRD followed by quantitative phase identification assessed the thermal transition to Cu-containing β-TCP. As Cu target incorporation increased from 0-5 mol% (actual 0-1.96 mol%), there was an observable increase in stoichiometry, carbonate removal, and resistance to thermal phase transition. Particle size, surface area, and degree of crystallinity measurements revealed significant deviation in surface area corresponding to only a 1.96 mol% increase in Cu content, yet miniscule modifications to crystallinity and particle size were observed. Heat treatment of CuHA to form Cu-containing biphasic calcium phosphate (CuBCP) enabled Cu release in aqueous solution whereby its CuHA counterpart showed no Cu release. Agar diffusion and time-based bacterial broth analyses were conducted against gram-positive and gram-negative strains of bacteria for CuHA and CuBCP. Some key structure-property relationships have been identified through this work.
Calcium phosphates, albeit adept at repairing hard tissue, are limited to non-load-bearing sites. Additionally, they are difficult to retrofit in the often unusually shaped bone defects. Ceramic-polymer composites are a better biological mimic of bone tissue, which itself is a composite. Polymerized high internal phase emulsion (polyHIPE) is a stochastic fabrication process that elicits highly interconnected and porous scaffolds, ideal for bone tissue regeneration. A 4-armed star-shaped photocurable polycaprolactone (PCL) is synthesized and functionalized with methacrylate end-groups to be used for UV-cured polyHIPE. The resultant polymer is characterized via Raman spectroscopy, attenuated total reflection- Fourier transform infrared spectroscopy (ATR-FTIR), and mass spectrometry (MS) to gain insight into the architecture of the macromolecule. Cured polyHIPEs exhibited excellent porosity, open-cell morphology, and interconnectedness, with pore size diameter of 108 ± 57μm. Efforts culminated with the attempted manufacture of a proof-of-concept next-generation bio-composite by incorporating HA into the polyHIPE. HA underwent surface modification to improve dispersion in the oil phase. However, HA caused a complete phase inversion of the emulsion. Nonetheless, the star-shaped PCL is characterized and this proof-of-concept bio-composite is described.
Description
Thesis completed in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Materials Science and Engineering at the Inamori School of Engineering, New York State College of Ceramics at Alfred University
Type
Thesis
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Keywords
Biomedical materials, Biomaterials, Polymers in medicine, Ceramics in medicine