OSTEOGENIC ACTIVITY OF ADDITIVE MANUFACTURED TITANIUM ALLOY-CALCIUM PHOSPHATE CERAMIC SCAFFOLDS FOR CRANIOPLASTY IN VITRO AND IN A LARGE ANIMAL CALVARIAL DEFECT MODEL

Jun 29, 2022, 12:20 PM
10m
Room: S2

Room: S2

Speaker

Nikody, Martyna (Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative)

Description

"Surgical repair of large skull bone defects is often performed using patient-specific metallic implants.(1) These implants, however, have poor osseointegration ability, and their life-long fixation is dependent on osteosynthesis screws.(2) It is often suggested that a composite model bone graft substitute could be used to overcome these problems, combining desired properties from individual material classes.(3) We recently developed new materials that combine the mechanical properties of a titanium alloy (Ti6Al4V) with the bioactivity of a calcium phosphate ceramic (CaP) using additive manufacturing, resulting in porous Ti6Al4V 3D implants without or containing 5 or 10 wt% beta-tricalcium phosphate (TCP).(4) The osteogenic differentiation and tissue formation capacity of bone marrow-derived human mesenchymal stromal cells (hMSCs) on these implants were examined in vitro, and the implants were subsequently tested in vivo in a large animal calvarial defect model.

Standardized cylindrical implants (diameter 5 mm, height 2 mm) were seeded with hMSCs and cultured in basic or mineralization medium. On days 14 and 28, the constructs were analyzed for cell metabolic activity, DNA content, tissue formation, alkaline phosphatase (ALP) activity, osteopontin and osteocalcin secretion, and osteogenic gene expression. Next, critical-size defects were made in the frontal bone of skeletally mature minipigs. Test or control scaffolds (diameter 15 mm, height 5 mm) were used for reconstruction, or the defect was left untreated. The animals were sacrificed after 12 weeks, and the implants were retrieved and analyzed for new bone formation and bone ingrowth.

hMSCs cultured on the scaffolds in vitro remained metabolically active and showed a similar proliferation profile on all scaffold types. hMSCs produced ALP, osteopontin and osteocalcin. Additionally, we observed tissue formation throughout the porous scaffolds in all conditions after 14 and 28 days. RUNX2 and ALP expression showed an inverted relationship with increasing TCP content, whereas osteocalcin and osteopontin were more expressed with increasing TCP content. A detailed analysis of the in vivo results of new bone formation and bone ingrowth into the porous structure is ongoing and results will be summarized in the presentation. Overall, the implants showed a good intra-operative handleability and no complications regarding the implant site were observed.

We have shown successful cell survival and tissue formation on our newly developed Ti6Al4V-TCP scaffold types in vitro. Bone formation and bone ingrowth into the 3D porous implant structure in the physiologically complex minipig model will enhance our understanding of the effect of the individual components and structural characteristics on the biological response.

  1. S. Honeybul et al., Acta Neurochir. 160, 885–891 (2018).
  2. B. Zanotti et al., J Craniofac Surg. 27, 2061–2072 (2016).
  3. M. Alizadeh-Osgouei et al., Bioact Mater. 4, 22–36 (2018).
  4. J. Li et al., Acta Biomater. 126, 496–510 (2021)."

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