Faculty Bibliography

WE43 Mg alloy proved to be an ideal candidate for production of resorbable implants in both clinical and trial settings. In previous studies we tested biocompatibility and degradation properties of WE43 (as-cast) and artificially aged (WE43-T5) Mg alloys in a sheep model. Both alloys showed excellent biocompatibility with the as-cast, WE43, form showing increased degradability compared to the artificially aged, WE43-T5. In the present study, our group assessed the biological behavior and degradation pattern of the same alloys when implanted as endosteal implants in a sheep model. Twelve screws (3x15 mm) were evaluated, one screw per each composition was placed bi-cortically in the mandible of each animal with a titanium (2x12 mm) screw serving as an internal positive control. At 6 and 24 weeks histomorphological analysis was performed, at 6 weeks as cast, WE43, yielded a higher degradation rate, increased bone remodeling and osteolysis compared to the WE43-T5 alloy; however, at 24 weeks WE43-T5 showed higher degradation rate and increased bone remodeling than as-cast. In vitro assay of cell growth, adhesion and differentiation was also conducted to investigate possible mechanisms underlying the behavior expressed from the alloys in vivo. In conclusion WE43-T5 indicated bone/implant interaction properties that makes it more suitable for fabrication of endosteal bone screws.

OBJECTIVE:To synthesize a zirconia toughened alumina (ZTA) composite with 70% alumina reinforced by 30% zirconia for dental applications and to characterize its microstructure and optical properties for comparison with the isolated counterpart materials and a first-generation 3Y-TZP. METHODS:Disc-shaped specimens were divided in four groups (n = 70/material): (1) 3YSB-E (first generation 3Y-TZP), (2) Zpex (second generation 3Y-TZP), (3) alumina, and (4) ZTA-Zpex 70/30. After synthesis, ceramic powders were pressed, and green-body samples sintered following a predetermined protocol. Specimens were polished to obtain a mirror surface finish. Apparent density was measured by Archimedes principle. X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to characterize the crystalline content and microstructure. Reflectance tests were performed to determine the contrast-ratio (CR) and translucency-parameter (TP). Mechanical properties were assessed by biaxial flexural strength (BFS) test. All analyses were conducted before and after artificial aging (20 h, 134 °C, 2.2 bar). Optical parameters were evaluated through repeated-measures analysis of variance and Tukey tests (p < 0.05). BFS data were analyzed using Weibull statistics (95% CI). RESULTS:High density values (95-99%) were found for all ceramic materials and SEM images exhibited a dense microstructure. While XRD patterns revealed the preservation of crystalline content in the ZTA composite, an increase in the monoclinic peak was observed for pure zirconias after aging. Significantly higher CR and lower TP values were observed for the ZTA composite, followed by alumina, 3YSB-E, and Zpex. The highest characteristic stress was recorded for 3YSB-E, followed by intermediate values between ZTA and Zpex, and the lowest for alumina. Aging affected the optical and mechanical properties of both zirconias, while remained stable for ZTA composite and alumina. SIGNIFICANCE/CONCLUSIONS:The synthesis of experimental 70-30% ZTA composite was successful and its relevance for dental applications relies on its higher masking ability, aging resistance, and strength similar to zirconia.

Literature has reported that up to 50% of dental implants may be affected by peri-implantitis, a bacteria-induced chronic inflammatory process, which promotes osteoclast-mediated bone resorption and inhibits bone formation, leading to progressive bone loss around implants. Current evidence points toward an increased risk for the development of peri-implantitis in both obesity/metabolic syndrome (MetS) and diabetes mellitus (DM) conditions relative to the healthy population. Currently, there is no effective treatment for peri-implantitis and the 50% prevalence in MetS and DM, along with its predicted increase in the worldwide population, presents a major concern in implant dentistry as hyperglycemic conditions are associated with bone-healing impairment; this may be through dysfunction of osteocalcin-induced glucose metabolism. The MetS/DM proinflammatory systemic condition and altered immune/microbiome response affect both catabolic and anabolic events of bone-healing that include increased osteoclastogenesis and compromised osteoblast activity, which could be explained by the dysfunction of insulin receptor that led to activation of signals related with osteoblast differentiation. Furthermore, chronic hyperglycemia along with associated micro- and macro-vascular ailments leads to delayed/impaired wound healing due to activation of pathways that are particularly important in initiating events linked to inflammation, oxidative stress, and cell apoptosis; this may be through deactivation of AKT/PKB protein, which possesses a pivotal role in drive survival and eNOS signaling. This review presents an overview of the local and systemic mechanisms synergistically affecting bone-healing impairment in MetS/DM individuals, as well as a rationale for hierarchical animal model selection, in an effort to characterize peri-implantitis disease and treatment.

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