Faculty Bibliography

Biomaterial scaffolds have served as the foundation of tissue engineering and regenerative medicine. However, scaffold systems are often difficult to scale in size or shape in order to fit defect-specific dimensions, and thus provide only limited spatiotemporal control of therapeutic delivery and host tissue responses. Here, a lithography-based 3D printing strategy is used to fabricate a novel miniaturized modular microcage scaffold system, which can be assembled and scaled manually with ease. Scalability is based on an intuitive concept of stacking modules, like conventional toy interlocking plastic blocks, allowing for literally thousands of potential geometric configurations, and without the need for specialized equipment. Moreover, the modular hollow-microcage design allows each unit to be loaded with biologic cargo of different compositions, thus enabling controllable and easy patterning of therapeutics within the material in 3D. In summary, the concept of miniaturized microcage designs with such straight-forward assembly and scalability, as well as controllable loading properties, is a flexible platform that can be extended to a wide range of materials for improved biological performance.

OBJECTIVES/OBJECTIVE:to evaluate the probability of survival and failure modes of lithium-disilicate, feldspathic-ceramic, and resin-nanoceramic anterior veneers cemented on dentin analog substrates after sliding-contact step-stress accelerated life testing (SSALT). METHODS:A virtual incisor tooth preparation was produced with a reduction of 1.5mm at the incisal edge and of 0.7mm buccally. A .STL file of the preparation was generated and CAD/CAM based G10 dentin-analog material was used for testing. Laminate veneers were milled in three different materials: lithium-disilicate (LDS, E.max CAD), resin-nanoceramic (RN, Lava Ultimate), and feldspathic-ceramic (FELDS, Vita Blocks). SSALT was employed where a spherical indenter contacted the veneer, slided along its interface with G10 to lift off and start a new cycle at 2Hz in water. Qualitative fractography was performed. The probability of survival (90% confidence-bounds) was calculated for several load/cycle missions. RESULTS:The probability of survival for a mission of 50,000 cycles decreased from 50 up to 150N equally for all groups and were not different between them. At 200N, the probability of survival was significantly lower for FELDS (10%) compared to RN veneers (41%), whereas LDS presented intermediate values (22%). The characteristic strength of RN (247N) was significantly higher than LDS (149N), and FELDS (151N). In FELDS and LDS, hackles, wake hackles and twist hackles indicated the direction of crack propagation. In RN, hackles were observed. CONCLUSIONS:Differences in probability of survival were observed only at 180 and 200N between groups. Failure modes were similar with veneer fracture down to the tooth-analog substrate.

BACKGROUND:Modification of endosteal implants through surface treatments have been investigated to improve osseointegration. Boronization has demonstrated favorable mechanical properties, but limited studies have assessed translational, in vivo outcomes. This study investigated the effect of implant surface boronization on bone healing. MATERIAL AND METHODS/METHODS:Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15µm boron coating was achieved. The surface-treated implants were placed bilaterally into 5 adult sheep ilia for three and six weeks. Four implant groups were tested: boronized machined (BM), boronized acid-etched (BAA), control machined (CM), and control acid-etched (CAA). Osseointegration was quantified by calculating bone to implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS:Both implant types treated with boronization had BIC values not statistically different from machined control implants at t=3 weeks, and significantly less than acid-etched control (p<0.02). BAFO values were not statistically different for all 3-week groups except machined control (significantly less at p <0.02). BAFO had a significant downward trend from 3 to 6 weeks in both boronized implant types (p<0.03) while both control implant types had significant increases in BIC and BAFO from 3 to 6 weeks. CONCLUSIONS:Non-decalcified histology depicted intramembranous-like healing/remodeling in bone for controls, but an absence of this dynamic process in bone for boronized implants. These findings are inconsistent with in vitro work describing bone regenerative properties of elemental Boron and suggests that effects of boron on in vivo bone healing warrant further investigation.

Bone grafting procedures have been widely utilized as the current state-of-the-art for bone regeneration, with autogenous bone graft being the gold-standard bone reconstructive option. However, the use of autografts may be limited by secondary donor-site comorbidities, a finite amount of donor supply, increased operating time, and healthcare cost impact. Synthetic materials, or alloplasts, such as the polymeric material, poly(lactic-co-glycolic acid) (PLGA) has previously been utilized as a transient scaffold to support healing of bone defects with the potential to locally delivery osteogenic additives. In this study a novel procedure was adopted to incorporate both the dissolved contents and mechanical components of leukocyte- and platelet-rich fibrin (L-PRF) into an PLGA scaffold through a two-step method: (a) extraction of the L-PRF membrane transudate with subsequent immersion of the PLGA scaffold in transudate followed by (b) delivering a fibrin gel as a low-viscosity component that subsequently polymerizes into a highly viscous, gel-like biological material within the pores of the PLGA scaffold. Two, ~0.40 cm³ , submandibular defects (n = 24) were created per side using rotary instrumentation under continuous irrigation in six sheep. Each site received a PLGA scaffold (Intra-Lock R&D, Boca Raton, FL), with one positive control (without L-PRF exudate addition [nL-PRF]), and one experimental (augmented with PLGA/L-PRF Blocks [L-PRF]). Animals were euthanized 6 weeks postoperatively and mandibles retrieved, en bloc, for histological analysis. Histomorphometric evaluation for bone regeneration was evaluated as bone area fraction occupancy (BAFO) within the region of interest of the cortical bone (with specific image analysis software) and data presented as mean values with the corresponding 95% confidence interval values. Qualitative evaluation of nondecalcified histologic sections revealed extensive bone formation for both groups, with substantially more bone regeneration for the L-PRF induced group relative nL-PRF group. Quantitative BAFO within the defect as function of the effect of L-PRF exudate on bone regeneration, demonstrated significantly (p = .018) higher values for the L-PRF group (38.26% ± 8.5%) relative to the nL-PRF group (~28% ± 4.0%). This in vivo study indicated that L-PRF exudate has an impact on the regeneration of bone when incorporated with the PLGA scaffold in a large translational model. Further studies are warranted in order to evaluate the L-PRF exudate added, as well as exploring the preparation methods, in order to facilitate bone regeneration.

Background/Purpose: b-Tricalcium phosphate (b-TCP), the most common synthetic bone replacement product, is frequently used in craniofacial reconstruction. Although solid b-TCP can be absorbed over time, the slow degradation rate (1%-3%/year) predisposes this product to exposure, infection, and fracture, limiting its use in the growing face where implants are required to grow and remodel with the patient. Our tissue engineering laboratory has successfully leveraged 3D printers to manufacture 3D-printed bioactive ceramic (3DPBC) scaffolds composed of b-TCP in an architecture which optimizes the needs of rigidity with efficient vascular ingrowth, osteogenesis, and degradation kinetics. The latter qualities are further optimized when the osteogenic agent dipyridamole (DIPY) is used. This long-term animal study reports on the new degradation kinetics profile achievable through this novel manufacturing and tissue engineering protocol. Methods/Description: Twenty-two 1-month-old (immature) New Zealand white rabbits underwent creation of unilateral 10 mm calvarial defects with ipsilateral 3.5 +/- 3.5 mm alveolar defects. Each defect was repaired with b-TCP 3DPBC scaffolds coated with 1000 mM DIPY. Rabbits were killed at 8 weeks (n = 6), 6 months (n = 8), and 18 months (n = 8). Bone regeneration and scaffold degradation were calculated using micro-CT images and analyzed in Amira software. Cranial and maxillary suture patency and bone growth were qualitatively analyzed using histologic analysis.
Result(s): Results are reported as a percentage of volumetric space occupied by either scaffold or bone. When comparing time points 8 weeks, 6 months, and 18 months, scaffolds showed significant decreased defect occupancy in calvaria (23.6% +/- 3.6%, 15.2% +/- 1.7%, 5.1% +/- 3.4%; P < .001) and in alveoli (21.5% +/- 3.9%, 6.7% +/- 2.7%, 0.1% +/- 0.2%; P < .001), with annual degradation rates 55.9% and 94.2%, respectively. Between 8 weeks and 18 months, significantly more bone regenerated in calvarial defects (25.8% +/- 6.3% vs 55.7% +/- 10.3%, P < .001) and no difference was found in alveolar defects (28.4% +/- 6.8% vs 32.4% +/- 8.0%, P = .33). Histology showed vascularized, organized bone without suture fusion.
Conclusion(s): The degradation kinetics of b-TCP can be altered through 3D printing and addition of an osteogenic agent. Our study demonstrates an acceleration of b-TCP degradation from 1% to 3% a year to 55% to 95% a year. Absorbed b-TCP is replaced by vascularized bone and there is no damage noted to the growing suture. This additive manufacturing and tissue engineering protocol has implication to future reconstruction of the craniofacial skeleton

PURPOSE/OBJECTIVE:To synthesize a zirconia-toughened alumina (ZTA) composite with 85% alumina matrix reinforced by 15% zirconia and to characterize its optical and mechanical properties before and after artificial aging, to be compared with a conventional dental zirconia (3Y-TZP). MATERIAL AND METHODS/METHODS:After syntheses, ZTA and 3Y-TZP powders were uniaxially and isostatically pressed. Green-body samples were sintered and polished to obtain 80 disc-shaped specimens per group (12 × 1 mm, ISO 6872:2015). The crystalline content and microstructure were characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). Optical properties were determined by the calculation of contrast ratio (CR) and translucency parameter (TP) using reflectance data. Mechanical properties were assessed by Vickers hardness, fracture toughness and biaxial flexural strength test (BFS). All analyses were conducted before and after artificial aging (20h, 134 °C, 0.22 MPa). Optical parameters and microhardness differences were evaluated through repeated-measures analysis of variance (p < 0.05). BFS data were analyzed using Weibull statistics (95% CI). RESULTS:The synthesis of the experimental ZTA composite was successful, with 98% of theoretical density, as shown in the SEM images. XRD patterns revealed typical zirconia and alumina crystalline phases. ZTA optical properties parameters showed no effect of aging, with a high CR and low TP values denoting a high masking-ability. 3Y-TZP presented lower masking-ability and aging significantly affected its optical properties. ZTA Vickers hardness, fracture toughness and Weibull parameters, including characteristic stress and Weibull modulus were not influenced by aging, while 3Y-TZP presented a significant decrease in characteristic stress and increase in fracture toughness after aging. The ZTA probability of survival for missions of 300 and 500 MPa was estimated at ~99% validating its use for 3-unit posterior fixed dental prostheses (FDP), and no different from conventional 3Y-TZP. At high-stress mission (800 MPa) a significant decrease in probability of survival was observed for aged 3Y-TZP (84%) and for immediate and aged ZTA (73 and 82% respectively). CONCLUSION/CONCLUSIONS:The ZTA composite presented a dense microstructure, with preservation of the crystalline content, optical and mechanical properties after artificial aging, which encourages future research to validate its potential use for large span FDP.

BACKGROUND:Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS:Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS:Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION/CONCLUSIONS:The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.

The reduced hardware design of narrow implants increases the risk of fracture not only of the implant itself but also of the prosthetic constituents. Hence, the current study is aimed at estimating the probability of survival of anterior crowns supported by different narrow implant systems. Three different narrow implant systems of internal conical connections were evaluated (Ø3.5 × 10 mm): (i) Active (Nobel Biocare), (ii) Epikut (S.I.N. Implant System), and (iii) BLX (Straumann). Abutments were torqued to the implants, and standardized maxillary incisor crowns were cemented. The assemblies were subjected to step-stress accelerated life testing (SSALT) in water through load application of 30 degrees off-axis lingually at the incisal edge of the crowns using a flat tungsten carbide indenter until fracture or suspension. The use level probability Weibull curves and reliability for completion of a mission of 100,000 cycles at 80 N and 120 N were calculated and plotted. Weibull modulus and characteristic strength were also calculated and plotted. Fractured samples were analyzed in a stereomicroscope. The beta (β) values were 1.6 (0.9-3.1) and 1.4 (0.9-2.2) for BLX and Active implants, respectively, and 0.5 (0.3-0.8) for the Epikut implant, indicating that failures were mainly associated with fatigue damage accumulation in the formers, but more likely associated with material strength in the latter. All narrow implant systems showed high probability of survival (≥95%, CI: 85-100%) at 80 and 120 N, without significant difference between them. Weibull modulus ranged from 6 to 14. The characteristic strength of Active, Epikut, and BLX was 271 (260-282) N, 216 (205-228) N, and 275 (264-285) N, respectively. The failure mode predominantly involved abutment and/or abutment screw fracture, whereas no narrow implant was fractured. Therefore, all narrow implant systems exhibited a high probability of survival for anterior physiologic masticatory forces, and failures were restricted to abutment and abutment screw.