Faculty Bibliography

OBJECTIVES/OBJECTIVE:To evaluate the clinical outcomes, histological parameters, and bone nanomechanical properties around implants retrieved from healthy and metabolic syndrome (MS) patients. METHODS:Twenty-four patients with edentulous mandibles (12/condition), received four implants between the mental foramina. An additional implant prototype was placed for retrieval histology. The following clinical outcomes were evaluated: insertion torque (IT), implant stability quotient (ISQ) values at baseline and after 60 days of healing, and implant survival. The prototype was retrieved after the healing and histologically processed for bone morphometric evaluation of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO), and bone nanoindentation to determine the elastic modulus (Em) and hardness (H). Descriptive statistical procedures and survival tests were used to analyze the data. RESULTS:The final study population was comprised of 10 women and 11 men (∼64 years). A total of 105 implants were placed, 21 retrieved for histology. Implant survival rates were similar between groups (>99 %). Similarly, IT and ISQ analyses showed no significant association with systemic condition (p > 0.216). Histological micrographs depicted similar bone morphology, woven bone, for both conditions. While MS (33 ± 5.3 %) and healthy (39 ± 6.5 %) individuals showed no significant difference for %BIC (p = 0.116), significantly higher %BAFO was observed for healthy (45 ± 4.6 %) relative to MS (30 ± 3.8 %) (p < 0.001). No significant differences on bone nanomechanical properties was observed (p > 0.804). CONCLUSIONS:Although no significant influence on clinical parameters and bone nanomechanical properties was observed, MS significantly reduced bone formation in the peri-implant area in the short-term. CLINICAL SIGNIFICANCE/CONCLUSIONS:A lower amount of bone formation in the peri-implant area was observed in comparison to healthy patients, although the other short-term clinical outcomes were not significantly different. Considering the escalating prevalence of MS patients in need for implant treatment, it becomes crucial to understand bone-to-implant response to determine the ideal loading time in this population.

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.

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

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.

AIM/OBJECTIVE:Die silicone materials are used to build chairside composite restorations. The purpose of this study was to compare the flowability, dimension accuracy, and tear strength of four elastomeric die materials. MATERIAL AND METHODS/METHODS:Materials were divided into four groups: Mach-2 (M2), Scan Die (SD), GrandioSO Inlay System (GIS), and Impregum-F (IM). Flowability analysis was carried out using the shark fin test (SFT). For dimension accuracy, impressions were taken from a premolar Class I preparation and an elastomeric model was cast. Composite resin restorations were built and positioned into the premolar for gap measurement. The mean gap length was divided into three levels: acceptable (A), not acceptable (NA), and misfit (M). For tear strength, strip specimens were made with a V-shaped notch (n = 6). The specimens were tested in a universal machine until tear. All data were analyzed statistically with a confidence interval of 95%. RESULTS:GIS showed the lowest flowability values, with no differences between IM, M2, and SD. For dimension accuracy, IM showed 100% 'A' gap values, followed by M2 (80%), SD (60%), and GIS (60%). For tear strength, IM showed the highest values, followed by M2, GIS, and SD. CONCLUSIONS:M2, SD, and IM had similar flowability, while GIS had the lowest. IM presented higher tear strength than M2, followed by GIS and SD. IM showed the highest degrees of acceptable gap filling, followed by M2.