Faculty Bibliography

Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (Vascular endothelial growth factor [VEGFR1]), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight coculture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that coculture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.

The purpose of this study was to assess vital bone formation at 4 to 5 months and 7 to 9 months following sinus augmentation with anorganic bovine bone matrix (ABBM) with and without recombinant human platelet-derived growth factor (rhPDGF). Twenty-four subjects received bilateral sinus elevation surgery with ABBM on one side and ABBM and rhPDGF on the contralateral side. Twelve patients had core sampling at 4 to 5 months and 12 patients at 7 to 9 months postoperatively. In subjects with cores taken at 4 to 5 months, mean vital bone, connective tissue, and residual graft were 11.8%, 54.1%, and 33.6%, respectively, with ABBM alone. Cores of sinuses filled with ABBM and rhPDGF showed mean 21.1% vital bone, 51.4% connective tissue, and 24.8% residual graft. Paired t test showed a statistically significant difference in vital bone. In cores taken at 7 to 9 months, the values for ABBM alone and ABBM + rhPDGF were 21.4% vs 19.5% vital bone, 28.4% vs 44.2% connective tissue, and 40.3% residual graft vs 35.5%. There was no statistically significant difference in vital bone at 7 to 9 months after surgery. Test and control groups showed clinically acceptable levels of vital bone both at 4 to 5 months and 7 to 9 months postsurgery. However, vital bone formation was significantly greater in the 4- to 5-month sections of ABBM + rhPDGF vs the Bio-Oss alone. In the 7- to 9-month specimens, this difference disappeared. More rapid formation of vital bone with the addition of rhPDGF may allow for earlier implant placement.

Understanding the life history correlates of ontogenetic differences in hominoid brain growth requires information from multiple species. At present, however, data on how brain size changes over the course of development are only available from chimpanzees and modern humans. In this study, we examined brain growth in wild Virunga mountain gorillas using data derived from necropsy reports (N = 34) and endocranial volume (EV) measurements (N = 86). The youngest individual in our sample was a 10-day-old neonatal male with a brain mass of 208 g, representing 42% of the adult male average. Our results demonstrate that Virunga mountain gorillas reach maximum adult-like brain mass by 3-4 years of age; adult-sized EV is reached by the time the first permanent molars emerge. This is in contrast to the pattern observed in chimpanzees, which despite their smaller absolute brain size, reportedly attain adult brain mass approximately 1 year later than Virunga mountain gorillas. Our findings demonstrate that brain growth is completed early in Virunga mountain gorillas compared to other great apes studied thus far, in a manner that appears to be linked with other life history characteristics of this population.

Microstructural data from the skeleton support the hypothesis that primate life histories are centrally regulated by a neuroendocrine rhythm, the Havers-Halberg Oscillation (HHO). However, subfossil lemurs are outliers in HHO scaling relationships which have been discovered for primates and mammals in general. We present new data to determine whether these species represent the general strepsirrhine condition and to inform general models about neuroendocrine-mediated life history evolution. We gathered the largest sample of HHO data from histological sections of primate teeth to date, regressing them against life history related variables such as body mass and basal metabolic rate. For all primates, mass and metabolic variables show strong and significant correlations with HHO in line with predictions. However, strepsirrhines do not follow this pattern when examined separately. Therefore, phylogeny may play an unforeseen role in governing how HHOs of specific taxa respond to ecological forces; in the case of the lemurs, which have been subjected to isolated ecologies due to living in Madagascar, these effects seem to have been especially potent. This reinforces the idea that HHO influences life history evolution in response to specific ecological selection regimes

The modern human face differs from that of our early ancestors in that the facial profile is relatively retracted (orthognathic). This change in facial profile is associated with a characteristic spatial distribution of bone deposition and resorption: growth remodeling. For humans, surface resorption commonly dominates on anteriorly-facing areas of the subnasal region of the maxilla and mandible during development. We mapped the distribution of facial growth remodeling activities on the 900-800 ky maxilla ATD6-69 assigned to H. antecessor, and on the 1.5 My cranium KNM-WT 15000, part of an associated skeleton assigned to African H. erectus. We show that, as in H. sapiens, H. antecessor shows bone resorption over most of the subnasal region. This pattern contrasts with that seen in KNM-WT 15000 where evidence of bone deposition, not resorption, was identified. KNM-WT 15000 is similar to Australopithecus and the extant African apes in this localized area of bone deposition. These new data point to diversity of patterns of facial growth in fossil Homo. The similarities in facial growth in H. antecessor and H. sapiens suggest that one key developmental change responsible for the characteristic facial morphology of modern humans can be traced back at least to H. antecessor.