Faculty Bibliography

Werner and Bloom syndromes are human diseases characterized by premature age-related defects including elevated cancer incidence. Using a novel Saccharomyces cerevisiae model system for aging and cancer, we show that cells lacking the RecQ helicase SGS1 (WRN and BLM homologue) undergo premature age-related changes, including reduced life span under stress and calorie restriction (CR), G1 arrest defects, dedifferentiation, elevated recombination errors, and age-dependent increase in DNA mutations. Lack of SGS1 results in a 110-fold increase in gross chromosomal rearrangement frequency during aging of nondividing cells compared with that generated during the initial population expansion. This underscores the central role of aging in genomic instability. The deletion of SCH9 (homologous to AKT and S6K), but not CR, protects against the age-dependent defects in sgs1Delta by inhibiting error-prone recombination and preventing DNA damage and dedifferentiation. The conserved function of Akt/S6k homologues in lifespan regulation raises the possibility that modulation of the IGF-I-Akt-56K pathway can protect against premature aging syndromes in mammals.

The structure and functional relationship of polymers have long been the purview of engineers and polymer chemists. Bioabsorbable fixation devices have been used for decades as dissolvable suture meshes and, recently, routinely by orthopedic surgeons. During the past decade, bioabsorbable fixation systems have become available for use by craniomaxillofacial surgeons for cranial vault remodeling. This study evaluates the application of a bioabsorbable fixation system in reconstructive craniofacial procedures in a pediatric population. We reviewed 146 cases of cranial vault reconstruction including 98 boys and 48 girls ranging from 2 months to 16 years (mean, 15 months) in age. The procedures were performed for 6 years between January 1998 and June 2004. Bioabsorbable plates and screws were used in each case; most of these cases were craniosynostosis reconstructions. There were 69 cases of frontal sagittal craniosynostosis, 36 metopic, 20 unicoronal, 12 bicoronal, 5 lamboid, 2 deformational plagiocephaly, and 2 multiple fusion of sutures. Postoperative evaluation consisted of clinical examination and three-dimensional computed tomography scan reconstructions at 3, 6, and 12 months. Items specifically screened for on the clinical examination included wound healing, signs of infection, and palpability of implant through the skin. Six patients had palpable plates, 2 patients had palpable screw, and 5 patients had infection at the incision site (of which only 3 were treated with inpatient care including incision drainage and intravenous antibiotics). Our experience has been overwhelmingly positive, and we feel that our results suggest that resorbable fixation is a superior option in pediatric plastic and craniofacial surgery.

One of the more interesting cells present in the umbilical cord blood - as far as their potential clinical use is concerned - are stem cells not presenting the CD34 antigen. These are the pluripotential cells with their biological properties similar to mesenchymal stem cells, with the ability to differentiate into such tissue types as bone, cartilage, nervous (to some extent), glia and muscle. The authors compared the activity of genes coding the proteins in mitogenic signal paths activated by kinin receptors using oligonucleotide microarrays in adherent and non-adherent CD 34- cells derived from umbilical cord blood. In the linear regression model with a 95% prognosis area for differentiating genes outside this area, the following genes were selected: c-jun (present in 3 isoforms) and c-fos. The fos and jun genes create the AP-1 transcriptive factor which regulates the expression of genes taking part in numerous cellular processes, including the cell cycle and mitosis. The obtained results shed some light on the molecular processes behind the MSC proliferation and are a starting point for further studies on the mesenchymal stem cell biology.

This study presents the in-vivo evaluation of Ti-13Nb-13Zr alloy implants obtained by the hydride route via powder metallurgy. The cylindrical implants were processed at different sintering and holding times. The implants' were characterized for density, microstructure (SEM), crystalline phases (XRD), and bulk (EDS) and surface composition (XPS). The implants were then sterilized and surgically placed in the central region of the rabbit's tibiae. Two double fluorescent markers were applied at 2 and 3 weeks, and 6 and 7 weeks after implantation. After an 8-week healing period, the implants were retrieved, non-decalcified section processed, and evaluated by electron, UV light (fluorescent labeling), and light microscopy (toluidine blue). BSE-SEM showed close contact between bone and implants. Fluorescent labeling assessment showed high bone activity levels at regions close to the implant surface. Toluidine blue staining revealed regions comprising osteoblasts at regions of newly forming/formed bone close to the implant surface. The results obtained in this study support biocompatible and osseoconductive properties of Ti-13Nb-13Zr processed through the hydride powder route. © 2007.

Objective: This series of laboratorial and in-vivo studies describe the characterization, evolution, and in-vivo performance of various Ca- and P-based nanothicknesses and microstructures ion beam assisted depositions (IBAD) onto Ti-6Al-4V implants. Materials and Methods: Characterization- The 4 mm in diameter and 10 mm in length implant rods (Ti-6Al-4V) with IBAD 1, IBAD 11, and control (alumina-blasted/acid-etched, AB/AE) surfaces were provided by an implant manufacturer. The in-vitro characterization comprised the following techniques: (1) SEM/EDS, (2) XPS/Depth Profiling (3) Thin-film XRD (4) AFM + ToF-SIMS for coating thickness determination (5) AFM- Ra determination. In-vivo- Three animal experiments were carried out for evaluation of the nanothickness bioceramic coatings. All experiments comprised a proximal tibia model with 4-6 implants placed along the bones. Times in-vivo ranged from 2-5 weeks. Static (bioactivity, bone to implant contact) and dynamic (mineral apposition rates- MAR) histomorphometric measurements were recorded. Biomechanical testing was performed by pullout and torque to interfacial failure testing. Results. Combination of the characterization techniques showed that all bioceramic coatings were Ca- and P-based bioceramics of amorphous microstructure. AFM +ToF-SIMS showed that IBAD 11 coatings were thicker (300-500 nm) compared to IBAD I coatings (30-50 nm). Surface roughness did not change significantly for the IBAD implant groups compared to control. The in-vivo results showed higher degrees of osseoactivity, torque to failure, and MAR for the coated implants at different times in-vivo. [BAD 11 had higher biomechanical fixation at early implantation times compared to other groups. Conclusions: The results obtained in the in-vitro part this study support that both IBAD I and IBAD 11 coatings are Ca- and P- based amorphous bioceramics in the nanothickness range with theoretical high dissolution rates. The increased osseoactivity observed for [BAD coated and the high MAR v allies observed for IBAD coated compared to AB/AE implants support the effect of the bioceramic coating presence in the overall bone healing. A thickness effect was reveled through biomechanical testing where IBAD 11 (300-500nm thickness) presented higher performance.