3D-ink-extruded titanium scaffolds with porous struts and bioactive supramolecular polymers for orthopedic implants

John P. Misiaszek*, Nicholas A. Sather, Alyssa M. Goodwin, Hogan J. Brecount, Steven S. Kurapaty, Jacqueline E. Inglis, Erin L. Hsu, Samuel I. Stupp, Stuart R. Stock, David C. Dunand

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Porous titanium addresses the longstanding orthopedic challenges of aseptic loosening and stress shielding. This work expands on the evolution of porous Ti with the manufacturing of hierarchically porous, low stiffness, ductile Ti scaffolds via direct-ink write (DIW) extrusion and sintering of inks containing Ti and NaCl particles. Scaffold macrochannels were filled with a subtherapeutic dose of recombinant bone morphogenetic protein-2 (rhBMP-2) alone or co-delivered within a bioactive supramolecular polymer slurry (SPS) composed of peptide amphiphile nanofibrils and collagen, creating four treatment conditions (Ti struts: microporous vs. fully dense; BMP-2 alone or with SPS). The BMP-2-loaded scaffolds were implanted bilaterally across the L4 and L5 transverse processes in a rat posterolateral lumbar fusion model. In-vivo bone growth in these scaffolds is evaluated with synchrotron X-ray computed microtomography (µCT) to study the effects of strut microporosity and added biological signaling agents on the bone formation response. Optical and scanning electron microscopy confirms the ∼100 µm space-holder micropore size, high-curvature morphology, and pore fenestrations within the struts. Uniaxial compression testing shows that the microporous strut scaffolds have low stiffness and high ductility. A significant promotion in bone formation was observed for groups utilizing the SPS, while no significant differences were found for the scaffolds with the incorporation of micropores. Statement of significance: By 2050, the anticipated number of people aged 60 years and older worldwide is anticipated to double to 2.1 billion. This rapid increase in the geriatric population will require a corresponding increase in orthopedic surgeries and more effective materials for longer indwelling times. Titanium alloys have been the gold standard of bone fusion and fixation, but their use has longstanding limitations in bone-implant stiffness mismatch and insufficient osseointegration. We utilize 3D-printing of titanium with NaCl space holders for large- and small-scale porosity and incorporate bioactive supramolecular polymers into the scaffolds to increase bone growth. This work finds no significant change in bone ingrowth via space-holder-induced microporosity but significant increases in bone ingrowth via the bioactive supramolecular polymers in a rat posterolateral fusion model.

Original languageEnglish (US)
Pages (from-to)446-459
Number of pages14
JournalActa Biomaterialia
Volume188
DOIs
StatePublished - Oct 15 2024

Funding

The authors acknowledge financial support from the National Science Foundation through grant DMR-2004769 and the National Science Foundation Graduate Fellowship Program through grant No. DGE-2234667 (for JPM). This work made use of the EPIC facilities of Northwestern University's NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-2025633 ), the MRSEC (Materials Research Science and Engineering Center) program (NSF DMR-1720139), the International Institute for Nanotechnology (IIN), and the State of Illinois, through the IIN. This work also made use of the Materials Characterization Laboratory (MatCI) and the Central Laboratory for Materials Mechanical Properties (CLaMMP), which received support from the MRSEC program ( NSF DMR-1720139 ). The biomaterial preparation and in vivo studies were supported by the Center for Regenerative Nanomedicine (CRN) at the Simpson Querrey Institute and also in part by the National Instibtute of Arthritis and Musculoskeletal and Skin Diseases Center of the National Institutes of Health under award number R01AR072721. Peptide amphiphile synthesis was performed at the Peptide Synthesis Core Facility of the Simpson Querrey Institute for BioNanotechnology at Northwestern University. This facility has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633). The Simpson Querrey Institute for BioNanotechnology, Northwestern University Office for Research, U.S. Army Research Office, and the U.S. Army Medical Research and Materiel Command have also provided funding to develop this facility. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. The authors thank Drs. Denis Keane and William (Mike) Guise for their assistance collecting and reconstructing data at the Advanced Photon Source, DND-CAT, beamline 5BM-C. The authors acknowledge financial support from the National Science Foundation through grant DMR-2004769 and the National Science Foundation Graduate Fellowship Program through grant No DGE-2234667 (for JPM). This work made use of the EPIC facilities of Northwestern University's NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the MRSEC (Materials Research Science and Engineering Center) program (NSF DMR-1720139), the International Institute for Nanotechnology (IIN), and the State of Illinois, through the IIN. This work also made use of the Materials Characterization Laboratory (MatCI) and the Central Laboratory for Materials Mechanical Properties (CLaMMP), which received support from the MRSEC program (NSF DMR-1720139). The biomaterial preparation and in vivo studies were supported by the Center for Regenerative Nanomedicine (CRN) at the Simpson Querrey Institute and also in part by the National Instibtute of Arthritis and Musculoskeletal and Skin Diseases Center of the National Institutes of Health under award number R01AR072721. Peptide amphiphile synthesis was performed at the Peptide Synthesis Core Facility of the Simpson Querrey Institute for BioNanotechnology at Northwestern University. This facility has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633). The Simpson Querrey Institute for BioNanotechnology, Northwestern University Office for Research, U.S. Army Research Office, and the U.S. Army Medical Research and Materiel Command have also provided funding to develop this facility. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No DE-AC02-06CH11357. The authors thank Drs. Denis Keane and William (Mike) Guise for their assistance collecting and reconstructing data at the Advanced Photon Source, DND-CAT, beamline 5BM-C.

Keywords

  • Direct-ink
  • Microporosity
  • Peptide amphiphile
  • Supramolecular polymer
  • Ti

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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