Faculty Bibliography

INTRODUCTION: Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system. METHODS: Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up. RESULTS: High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages. CONCLUSIONS: Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. (c) 2013 S. Karger AG, Basel.

Objectives. To test the hypothesis that there would be no differences in osseointegration by reducing the number of drills for site preparation relative to conventional drilling sequence. Methods. Seventy-two implants were bilaterally placed in the tibia of 18 beagle dogs and remained for 1, 3, and 5 weeks. Thirty-six implants were 3.75 mm in diameter and the other 36 were 4.2 mm. Half of the implants of each diameter were placed under a simplified technique (pilot drill + final diameter drill) and the other half were placed under conventional drilling where multiple drills of increasing diameter were utilized. After euthanisation, the bone-implant samples were processed and referred to histological analysis. Bone-to-implant contact (BIC) and bone-area-fraction occupancy (BAFO) were assessed. Statistical analyses were performed by GLM ANOVA at 95% level of significance considering implant diameter, time in vivo, and drilling procedure as independent variables and BIC and BAFO as the dependent variables. Results. Both techniques led to implant integration. No differences in BIC and BAFO were observed between drilling procedures as time elapsed in vivo. Conclusions. The simplified drilling protocol presented comparable osseointegration outcomes to the conventional protocol, which proved the initial hypothesis.

Lateral or vertical bone augmentation has always been a challenge, since the site is exposed to constant pressure from the soft tissue, and blood supply only exists from the donor site. Although, for such clinical cases, onlay grafting with autogenous bone is commonly selected, the invasiveness of the secondary surgical site and the relatively fast resorption rate have been reported as a drawback, which motivated the investigation of alternative approaches. This study evaluated the bone-forming capability of a novel nanoHA alloplast infused with collagen graft material made from biodegradable polylactic acid/polyglycolic acid versus a control graft material with the same synthesized alloplast without the nanoHA component and collagen infiltration. The status of newly formed bone and the resorption of the graft material were evaluated at 6 weeks in vivo histologically and three dimensionally by means of 3D microcomputed tomography. The histologic observation showed that newly formed bone ingrowth and internal resorption of the block were observed for the experimental blocks, whereas for the control blocks less bone ingrowth occurred along with lower resorption rate of the block material. The three-dimensional observation indicated that the experimental block maintained the external geometry, but at the same time successfully altered the graft material into bone. It is suggested that the combination of numerous factors contributed to the bone ingrowth and the novel development could be an alternative bone grafting choice.