Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells.

BACKGROUND: Craniomaxillofacial defects secondary to trauma, tumor resection, or congenital malformations are frequent unmet challenges, due to suboptimal alloplastic options and limited autologous tissues such as bone. Significant advances have been made in the application of adipose-derived stem/stromal cells (ASCs) in the pre-clinical and clinical settings as a cell source for tissue engineering approaches. To fully realize the translational potential of ASCs, the identification of optimal donors for ASCs will ensure the successful implementation of these cells for tissue engineering approaches. In the current study, the impact of obesity on the osteogenic differentiation of ASCs was investigated. METHODS: ASCs isolated from lean donors (body mass index <25; lnASCs) and obese donors (body mass index >30; obASCs) were induced with osteogenic differentiation medium as monolayers in an estrogen-depleted culture system and on three-dimensional scaffolds. Critical size calvarial defects were generated in male nude mice and treated with scaffolds implanted with lnASCs or obASCs. RESULTS: lnASCs demonstrated enhanced osteogenic differentiation in monolayer culture system, on three-dimensional scaffolds, and for the treatment of calvarial defects, whereas obASCs were unable to induce similar levels of osteogenic differentiation in vitro and in vivo. Gene expression analysis of lnASCs and obASCs during osteogenic differentiation demonstrated higher levels of osteogenic genes in lnASCs compared to obASCs. CONCLUSION: Collectively, these results indicate that obesity reduces the osteogenic differentiation capacity of ASCs such that they may have a limited suitability as a cell source for tissue engineering.

The blood supply to the canine middle ear.

Current descriptions of the anatomy of the blood supply to the canine middle ear are either incomplete or inconsistent, particularly in regards to the vascular branches in close proximity to the temporomandibular articulation (TMJ). To further investigate this blood supply, dissections (n = 9), corrosion casts (n = 4), and computed tomography (n = 8) of canine temporal regions/ears were performed. The goal of this study was to identify and describe branches of the external carotid and maxillary arteries in close proximity to the TMJ that supply the middle ear of the dog. Specific focus was placed on the constancy and origin of the canine rostral tympanic artery since this artery was anticipated to arise from the maxillary artery and enter a foramen at the medial aspect of the mandibular fossa adjacent to the TMJ. New anatomical variations of three canine arteries are described in this study. (1) The rostral tympanic artery is a branch of the temporomandibular ramus and is accommodated by a small foramen located within a depression medial to the temporomandibular joint. (2) A pharyngeal branch of the caudal deep temporal artery was identified. (3) The origin of the caudal auricular artery occurred opposite the lingual artery in 25.8% of dissected specimens, contrary to published descriptions. Anat Rec, 299:907-917, 2016. © 2016 Wiley Periodicals, Inc.

Sclerostin antibody treatment improves implant fixation in a model of severe osteoporosis.

BACKGROUND: The mechanical fixation of orthopaedic and dental implants is compromised by diminished bone volume, such as with osteoporosis. Systemic administration of sclerostin antibody (Scl-Ab) has been shown to enhance implant fixation in normal animals. In the present study, we tested whether Scl-Ab can improve implant fixation in established osteoporosis in a rat model. METHODS: We used an ovariectomized (ovx) rat model, in which we found a 78% decrease in trabecular bone volume at the time of implant surgery; sham-ovx, age-matched rats were used as controls. After placement of a titanium implant in the medullary cavity of the distal aspect of the femur, the rats were maintained for four, eight, or twelve weeks and treated biweekly with Scl-Ab or with the delivery vehicle alone. Outcomes were measured with use of microcomputed tomography, mechanical testing, and static and dynamic histomorphometry. RESULTS: Scl-Ab treatment doubled implant fixation strength in both the sham-ovx and ovx groups, although the enhancement was delayed in the ovx group. Scl-Ab treatment also enhanced bone-implant contact; increased peri-implant trabecular thickness and volume; and increased cortical thickness. These structural changes were associated with an approximately five to sevenfold increase in the bone-formation rate and a >50% depression in the eroded surface following Scl-Ab treatment. Trabecular bone thickness and bone-implant contact accounted for two-thirds of the variance in fixation strength. CONCLUSIONS: In this model of severe osteoporosis, Scl-Ab treatment enhanced implant fixation by stimulating bone formation and suppressing bone resorption, leading to enhanced bone-implant contact and improved trabecular bone volume and architecture. CLINICAL RELEVANCE: Systemic administration of anti-sclerostin antibodies might be a useful strategy in total joint replacement when bone mass is deficient.