Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Bone defects resulting from trauma or infection need timely and effective treatments to replace damaged bone. Using specialized three-dimensional (3-D) printing technology, combined with bioactive molecules, we can design custom 3-D scaffolds for bone repair. The Hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (b-TCP) scaffold components provide mechanical strength, conduct bone throughout the scaffold and remodel over time. Adenosine, acting via adenosine receptors (A1, A2A, A2B and A3), plays a critical role in regulating bone metabolism. Dipyridamole (DIPY) increases local adenosine levels by blocking cellular uptake of adenosine and stimulates bone regeneration. We tested the capacity of dipyridamole, hypothesize that with a bioactive filler, such as DIPY, these scaffolds may successfully regenerate bone over critical sized bone defects in an in vivo model.
Methods: 15% HA:85% b-TCP scaffolds were designed using Robocad software, fabricated using a 3-D Robot, and sintered at 1100°C for 4h. SEM and microCT were used to examine structural aspects on pre/post-sintering, while XRD, FT-IR and ICP were used to evaluate porosity, crystalline phase quantification, and Ca:P ratio, respectively. Vehicle, BMP-2 and combination drug scaffolds (calcium sulfate + drug, calcium sulfate + drug in solution, collagen + drug in solution) were implanted in C57B6 mice with 3mm critical size defect for 2 weeks. DIPY release from scaffold was assayed in vitro spectrophotometrically over time. MicroCT and histological analysis were conducted to determine the degree of new bone formation and remodeling.
Results: Qualitative microstructural evaluation using SEM showed a broader pore/particle size distribution for materials sintered. The x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and inductive coupled plasma (ICP) results showed substantial deviations in the original 15/85% HA/b-TCP formulation with the detection of ~10%calcium pyrophosphate. Also, as sintering temperature was increased, lower amounts of the HA (5% HA: ~95% b-TCP) phase was observed. DIPY release assays showed a constant 10 -6M release of the compound for a period of 10 days. Quantitative and qualitative results from microCT showed similar and significant bone formation and remodeling in HA/b-TCP- DIPY and HA/b-TCP-BMP-2 scaffolds (p=NS) when compared to vehicle 2 weeks after surgery. Histological analysis showed increased bone formation and osteoconduction in HA/b-TCP- DIPY scaffolds.
Conclusion: Results from the in vitro and in vivo studies demonstrate that HA/b-TCP- DIPY scaffolds are highly biocompatible and can rapidly and successfully regenerate and remodel bone in critical size defects.
Disclosure:
S. Ishack,
None;
A. Mediero,
Filed a patent on use of adenosine A2AR agonists to prevent prosthesis loosening (pending). ,
9;
T. Wilder,
None;
J. Ricci,
None;
B. N. Cronstein,
Canfite Pharma,
1,
NIH, Gilead, Takeda, AstraZeneca,
2,
NYU School of Medicine,
3,
Merck-SeronoBristol-Myers Squibb, Novartis, CanFite Biopharmaceuticals, Cypress Laboratories, Regeneron (Westat, DSMB), Endocyte, Protalex, Allos, Inc., Savient, Gismo Therapeutics, Antares Pharmaceutical, Medivector,
5,
Multiple patents on adenosine receptors and bone metabolism, pharmacology,
9.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-use-of-three-dimensionally-printed-%ce%b2-tricalcium-phosphatehydroxyapatite-to-understand-the-regulation-of-adenosine-receptors-in-osteoclast-formation-and-promotion-in-bone-regeneration/