Transforming the Degradation Rate of β-tricalcium Phosphate Bone Replacement Using 3-Dimensional Printing

Abstract

Background β-Tricalcium phosphate (β-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of β-TCP. Methods Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed β-TCP scaffolds coated with 1000 μM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. Results Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. Conclusions Our study demonstrates an improved degradation profile and replacement of absorbed β-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.

3D-Printed Hydroxyapatite and Tricalcium Phosphates-Based Scaffolds for Alveolar Bone Regeneration in Animal Models: A Scoping Review

“…The included studies followed the Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines for quality assessment in this review [ 36 ]. The 10 selected articles were published between 2016 and 2021 and were conducted in the USA (n = 4) [ 37 , 38 , 39 , 40 ], Taiwan (n = 2) [ 41 , 42 ], Korea (n = 2) [ 43 , 44 ], China (n = 1) [ 45 ] and Switzerland (n = 1) [ 46 ]. Table 1 and Table 2 summarize the details of the included studies using 3D HA-based and 3D TCP-based scaffolds.…”

“…Eight out of ten studies used large animal models, which were beagle dogs [ 43 , 44 , 46 ], canines [ 37 ] and rabbits [ 38 , 39 , 40 , 45 ], whereas the other two used small animal models, Sprague-Dawley rats, in their studies [ 41 , 42 ] ( Table 3 ). Tooth extraction of lower premolars and molars was carried out with a healing period of 6 to 12 weeks prior to defects’ preparation [ 37 , 43 , 46 ].…”

“…Tooth extraction of lower premolars and molars was carried out with a healing period of 6 to 12 weeks prior to defects’ preparation [ 37 , 43 , 46 ]. Eight studies involved surgically created defects on the mandible [ 37 , 38 , 41 , 42 , 43 , 44 , 45 , 46 ] and the remaining two studies were on the maxilla [ 39 , 40 ] to receive either 3D-printed HA-based or TCP-based bone scaffolds.…”

“…Three studies reported a combination of four interventions: 3D-printed HA and RGD-functionalized alginate matrix (RAM) as a supplement [ 42 ], 3D-printed HA with additional features of microchannels or macro-channels with or without a screw [ 37 ] and 3D-printed TCP and calcium silicate porous bioceramics [ 45 ]. Six studies were designed to have negative control groups, which were unfilled or untreated bone defects [ 38 , 39 , 40 , 41 , 42 , 43 ], and one positive control group [ 43 ]. Two studies reported the blinding of the treatment assignment to the surgical procedures [ 41 , 42 ].…”

“…The other two studies used combinations of tricalcium phosphates as the experimental materials, which were α-TCP and calcium-deficient HA (CDHA) (OsteoFlux ® , Vivos-Dental, Villaz-St-Pierre, Switzerland) [ 46 ], and HA and TCP [ 43 ]. Four articles documented using β-TCP only [ 38 , 39 , 40 , 45 ] and one article used plain HA (TheriRidge) as bone scaffolds [ 37 ]. There was only one study reporting the application method of the adipose stem cells’ seeding prior to implantation of the 3D-printed TCP-based scaffolds [ 44 ].…”