Faculty Bibliography

Strain rate dependence of the mechanical response of hard tissues has led to a keen interest in their dynamic properties. The current study attempts to understand the high strain rate characteristics of rabbit femur bones. The testing was conducted using a split-Hopkinson pressure bar equipped with a high speed imaging system to capture the fracture patterns. The bones were also characterized under quasi-static compression to enable comparison with the high strain rate results. The quasi-static compressive moduli of the epiphyseal and diaphyseal regions were measured to be in the range of 2-3 and 5-7GPa, respectively. Under high strain rate loading conditions the modulus is observed to increase with strain rate and attains values as high as 15GPa for epiphyseal and 30GPa for diaphyseal regions of the femur. The strength at high strain rate was measured to be about twice the quasi-static strength value. A large number of small cracks initiated on the specimen surface close to the incident bar. Coalescence of crack branches leading to fewer large cracks resulted in specimen fragmentation. In comparison, the quasi-static failure was due to shear cracking.

The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1alpha (HIF-1alpha) up-regulation in endothelial cells (ECs), a HIF-1alpha-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1alpha and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1alpha mRNA and abolition of HIF-1alpha protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1alpha induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis

Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/t-test was used to determine significance (p</= 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18+/-1.3 d in the treated group vs. 28+/-1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3+/-13.9 pg/mL) vs. controls (33.0+/-3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA

Chronic post-surgical lymphedema is common condition that afflicts nearly 2 million Americans. In the USA, it is most commonly encountered in the upper extremities of patients who have undergone axillary lymph node dissection for breast cancer. Lymphedema has a significant negative effect on cosmesis, limb function, and overall quality of life. Despite the impact of this condition, very little is known about how to effectively prevent or treat lymphedema. While therapeutic options for chronic extremity lymphedema remain limited, several surgical approaches have been suggested. These include techniques aimed at reducing limb volume, as well as techniques that aim to reconstitute disrupted lymphatic channels. Operations proposed to re-establish lymphatic continuity include lymphatico-venous anastomoses, lymphatico-lymphatico anastomoses, and tissue transfer.

BACKGROUND: Recent reports have demonstrated that lymphedema can occur after even minor pertubation of the axillary region such as sentinel lymph node biopsy (SLNB). The impact of breast reconstruction on the development of lymphedema, however, remains unknown. Therefore, the purpose of this study was to determine the impact of immediate tissue expander breast reconstruction on the risk of developing lymphedema. MATERIALS AND METHODS: We identified patients who had undergone mastectomy with SLNB or SLNB and axillary lymph node dissection (ALND) with or without breast reconstruction using our prospectively maintained lymphedema and breast reconstruction databases. The development of lymphedema was evaluated prospectively using arm measurements and a validated questionnaire. Associations between variables were examined. Logistic regression was used to examine the association of reconstruction on prevalence of lymphedema while adjusting individually for BMI, age, and weight gain after surgery. RESULTS: Characteristics of patients with or without reconstruction were similar except for age, BMI, and weight gain since surgery. Median follow-up was 5 years. Among patients treated with mastectomy with SLNB or SLNB/ALND, those undergoing reconstruction had a lower rate of measured lymphedema than those who did not (5% vs. 18%, P < .0004). The reconstructed group also had fewer patients with both measured and self-reported lymphedema (3% vs. 12%, P < .002). Differences in the rates of measured lymphedema between groups persisted following univariate logistical regression for differences in age, BMI, and weight gain. CONCLUSIONS: Tissue expander breast reconstruction in patients undergoing SLNB or SLNB/ALND does not increase the risk of developing measured or perceived lymphedema.

Mesenchymal and hematopoietic tissues are important reservoirs of adult stem cells. The potential of tissue resident mesenchymal stem cells (MSCs) to differentiate into cells of mesodermal and ectodermal lineages has been reported previously. We examined the hypothesis that adherent adipose tissue resident mesenchymal stem cells (ASCs) are capable of generating cells with hematopoietic characteristics. When cultured in differentiation media, clonally isolated ASCs develop into cells with hematopoietic attributes. The hematopoietic differentiated cells (HD) express early hematopoietic (c-kit, PROM1, CD4) as well as monocyte/macrophage markers (CCR5, CD68, MRC1, CD11b, CSF1R). Additionally, HD cells display functional characteristics of monocyte/macrophages such as phagocytosis and enzymatic activity of α-Naphthyl Acetate Esterase. HD cells are also responsive to stimulation by IL-4 and LPS as shown by increased CD14 and HLA-DRB1 expressions and release of IL-2, IL10, and TNF. Taken together, this study characterizes the potential of ASCs to generate functional macrophages in vitro, and therefore paves way for their possible use in cell therapy applications.

It is a general consideration to maintain bone around the dental implant. This is very necessary for the long term success of the implant. In earlier times osseointegration was thought to an element of success for implant but it does not necessarily indicate that this bone material interface will keep its integrity throughout the patient life. There can be so many contributing factors for the bone loss. So this article deals with all the factor related to crestal bone loss. [ABSTRACT FROM AUTHOR]