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

Acta Biomater. 2024 Oct 15:188:446-459. doi: 10.1016/j.actbio.2024.09.004. Epub 2024 Sep 12.

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.

Keywords: Direct-ink; Microporosity; Peptide amphiphile; Supramolecular polymer; Ti.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2* / chemistry
  • Bone Morphogenetic Protein 2* / pharmacology
  • Humans
  • Polymers / chemistry
  • Polymers / pharmacology
  • Porosity
  • Printing, Three-Dimensional
  • Prostheses and Implants
  • Rats
  • Rats, Sprague-Dawley*
  • Recombinant Proteins / pharmacology
  • Tissue Scaffolds* / chemistry
  • Titanium* / chemistry
  • Titanium* / pharmacology
  • Transforming Growth Factor beta
  • X-Ray Microtomography

Substances

  • Titanium
  • Bone Morphogenetic Protein 2
  • Polymers
  • recombinant human bone morphogenetic protein-2
  • Recombinant Proteins
  • Transforming Growth Factor beta