Biomaterials for Orthopaedic Diagnostics and Theranostics

Abstract

Despite widespread use of conventional diagnostic methods in orthopaedic applications, limitations still exist in detection and diagnosing many pathologies especially at early stages when intervention is most critical. The use of biomaterials to develop diagnostics and theranostics, including nanoparticles and scaffolds for systemic or local applications, has significant promise to address these shortcomings and enable successful clinical translation. These developments in both modular and holistic design of diagnostic and theranostic biomaterials may improve patient treatments for myriad orthopaedic applications ranging from cancer to fractures to infection.

Figure 1:. Overview of clinical needs for diagnostic/theranostic biomaterials and example materials.

A) Representative clinical images of orthopaedic applications. B, C) Systemic and local biomaterials highlighted in this review. PLGA: Poly(lactic acid-co-glycolic acid), PCL/PS: Poly(caprolactone)/calcium silicate. Porphysome is reproduced from [13] (https://pubs.acs.org/doi/10.1021/nn400669r) with permission. Further permission related to the material excerpted should be directed to the ACS. BP-targeted PLGA Nanoparticles reprinted with permission from [14]: Low SA, Galliford CV, Yang J, Low PS, Kopeček J. Biodistribution of Fracture-Targeted GSK3β Inhibitor-Loaded Micelles for Improved Fracture Healing. Biomacromolecules. 2015;16(10):3145–53. doi: 10.1021/acs.biomac.5b00777. Copyright 2015 American Chemical Society. Alkaline phosphatase detecting PCL/PS Scaffold Originally published in [15] reprinted from Chemical Engineering Journal, 408, Yang C, Gao X, Younis MR, Blum NT, Lei S, Zhang D, Luo Y, Huang P, J Lin J, Non-invasive monitoring of in vivo bone regeneration based on alkaline phosphatase-responsive scaffolds, 127959, Copyright 2021, with permission from Elsevier under CC BY-NC 4.0 license #5036610232181. Oxygen-detecting poly(caprolactone) scaffolds reprinted with permission from [16]: Schilling K, El Khatib M, Plunkett S, Xue J, Xia Y, Vinogradov SA, Brown E, Zhang X. Electrospun Fiber Mesh for High-Resolution Measurements of Oxygen Tension in Cranial Bone Defect Repair. ACS Appl Mater Interfaces. 2019 Sep 18;11(37):33548–33558. Copyright 2019 American Chemical Society. Strontium-doped hydroxyapatite-collagen scaffold image [17] is reproduced under CC BY-NC 4.0 license #5036610940442. Center skeleton is from [18].

Figure 2:. Schematic representation of systemically delivered NP-based biomaterials used in diagnostics and theranostic for orthopaedic applications detailing the features that can be modulated.

SWCNT, single-walled carbon nanotubes; QDs, quantum dots; UCNPs, upconversion nanoparticles; GNPs, gold nanoparticles, SPIONs, superparamagnetic nanoparticles, MeSiNPs, mesoporous silica nanoparticles; HA NPs, hydroxyapatite nanoparticles. Figure adapted from [49].