Osteocyte numbers decrease only in postcranial but not in cranial bones in humans of advanced age.

BACKGROUND: Bone ageing is governed by the linked activities of short-lived osteoblasts and osteoclasts in conjunction with long-lived osteocytes present in osseous structure. Besides their maintenance function, osteogenic cells also gain specific positional information, which may potentially trigger ageing-associated cellular deviations in terminally differentiated osteocytes differently in cranial versus postcranial tissues. METHODS: We therefore investigated bone taken from deceased aged humans explanted at five distinct anatomical positions throughout the body and assessed physical and biological determinants applying radiologic and histologic measures. RESULTS: We were able to show that significantly more osteocytes reside in aged cortical bone at cranial positions than within axial or limb skeleton. These cellular states and conditions were not found in the corresponding trabecular bone, where osteocyte numbers remain also high at postcranial positions. Parallel comparative analyses of bone microstructure as analyzed by means of computer tomography showed no significant differences. CONCLUSIONS: Considering differences and commonalities regarding the bone samples, such as loading, mechanisms of ossification or the surrounding stromal cell compartment, our findings indicate that positional information laid down during ontogenetic processes is instructive during the entire life thus potentially also moulding spatial-specific mechanistic distinctions of bone ageing.

Hard Tissue Augmentation of Aged Bone by Means of a Tin-Free PLLA-PCL Co-Polymer Exhibiting in vivo Anergy and Long-Term Structural Stability.

BACKGROUND: Due to aging, tissue regeneration gradually declines. Contemporary strategies to promote tissue-specific regeneration, in particular in elderly patients, often include synthetic material apt for implantation primarily aiming at upholding body functions and regaining appropriate anatomical and functional integrity. OBJECTIVE: Biomaterials suitable for complex reconstruction surgical procedures have to exert high physicochemical stability and biocompatibility. METHOD: A polymer made of poly-L-lactic acid and poly-ε-caprolactone was synthesized by means of a novel tin-free catalytic process. The material was tested in a bioreactor-assisted perfusion culture and implanted in a sheep model for lateral augmentation of the mandible. Histological and volumetric evaluation was performed 3 and 6 months post-implantation. RESULTS: After synthesis the material could be further refined by cryogrinding and sintering, thus yielding differently porous scaffolds that exhibited a firm and stable appearance. In perfusion culture, no disintegration was observed for extended periods of up to 7 weeks, while mesenchymal stromal cells readily attached to the material, steadily proliferated, and deposited extracellular calcium. The material was tested in vivo together with autologous bone marrow-derived stromal cells. Up to 6 months post-implantation, the material hardly changed in shape with composition also refraining from foreign body reactions. CONCLUSION: Given the long-term shape stability in vivo, featuring imperceptible degradation and little scarring as well as exerting good compatibility to cells and surrounding tissues, this novel biomaterial is suitable as a space filler in large anatomical defects.

Pervasion of beta-tricalcium phosphate with nanodiamond particles yields efficient and safe bone replacement material amenable for biofunctionalization and application in large-size osseous defect healing.

Biofunctionalization of scaffold materials can enable the healing of large bone defects. In case of minimally invasive guided-bone regeneration (GBR), limitations are however hard-to-control side effects related to the potential release of biofactors into the systemic environment. Biofactors can be stably bound to nanodiamond particles (ND) through physisorption. We therefore tested the biological and clinical effects of refining beta-tricalcium phosphate (ßTCP) with ND in vitro and in vivo. In vitro, ßTCP carrying 4% ND resulted in enhanced attachment of mesenchymal stem cells. When assessing GBR after lateral augmentation of the mandible in sheep showed that ND in ßTCP resulted in a consistently steady bone formation when compared to pure ßTCP, demonstrating the biological inert behavior and the potential clinical safety of ND.

Long-lived murine osteocytes are embodied by craniofacial skeleton in young and old animals whereas they decrease in number in postcranial skeletons at older ages.

BACKGROUND: Osteocytes are engaged in life-enduring processes such as bone remodelling, fracture healing or osseointegration of implants. Over age, ossification processes and regenerative capacity can greatly differ in mandible and femur. OBJECTIVE: Mesenchymal stem cells from cranial and postcranial bones are of different embryologic origin. This may be the reason why the regenerative capacity differs between cranial and postcranial bones in old patients. It was hypothesised that different ageing patterns, reflected by osteocyte density, lacunar density and osteoid formation, exist between murine mandibles and femurs. MATERIAL AND METHODS: Mandible and femur of young (4 months) and old (34-36 months old) male C57Bl/6 mice were histologically investigated to determine the number of lacunae occupied with osteocytes. Osteoid formation was revealed by Masson-Goldner staining, and the spatial distribution of BMP-2 synthesis was examined. RESULTS: Over lifetime, the number of lacunae occupied with osteocytes only showed a modest decrease in mandibular bone (old 85.63%/young 91.12%) while greatly diverging in the femur (old 55.99%/young 93.28%). In equal measure, old femur exhibited less osteoid formation and decreased BMP-2 expression. CONCLUSION: Tissue-specific conduct of bone ageing is moulded by osteocytic activities, which was found to vary between postcranial and craniofacial skeleton. The latter harbours long-lived osteocytes also in old animals which assures lifelong bone integrity. Preliminary concurring findings from a human cadaver, also presented in this contribution, provided a rationale for recommending the translatability to humans.

How meta-analytic evidence impacts clinical decision making in oral implantology: a Delphi opinion poll.

OBJECTIVES: To investigate the impact of meta-analytic evidence in scientific literature on clinical decision making in the field of oral implantology. METHODS: A Delphi opinion poll was performed at the meeting of the "Next Generation" Committees of the Austrian, German and Swiss Societies for Implantology (ÖGI, DGI and SGI). First, the experts gave their opinion on 20 questions regarding routine implant treatment (uninformed decisions), then they were confronted with up-to-date Level I evidence from scientific literature on these topics and again asked to give their opinion (informed decisions) as well as to rate the available evidence as satisfactory or insufficient. Topics involved surgical issues, such as immediate implant placement, flapless surgery, tilted and short implants and bone substitute materials, as well as opinions on prosthodontic paradigms, such as immediate loading, abutment materials and platform switching. RESULTS: Compared to their uninformed decisions prior to confrontation with recent scientific literature, on average, 37% of experts (range: 15-50%) changed their opinion on the topic. When originally favoring one treatment alternative, less than half were still convinced after review of meta-analytic evidence. Discrepancy between uninformed and informed decisions was significantly associated with insufficient evidence (P = 0.014, 49% change of opinion vs. 26% on topics rated as sufficiently backed with evidence). Agreement regarding strength of evidence could be reached for eight topics (40%), in three issues toward sufficiency and in five issues toward lack of evidence. CONCLUSION: Confrontation with literature results significantly changes clinical decisions of implantologists, particularly in cases of ambiguous or lacking meta-analytic evidence.

In vivo investigation on connective tissue healing to polished surfaces with different surface wettability.

OBJECTIVES: Connective tissue in contact to transgingival/-dermal implants presents itself as tight scar formation. Although rough surfaces support the attachment they increase bacterial colonisation as well. In contrast to surface roughness, little is known about the influence of surface wettability on soft-tissue healing in vivo. We therefore investigated the influence of different surface wettabilities on connective tissue healing at polished implant surfaces in vivo. MATERIAL AND METHODS: Three polished experimental groups (titanium, titanium coated with hydrophobic nano-crystalline diamond (H-NCD) and titanium coated with hydrophilic nano-crystalline diamond (O-NCD) were inserted into the subcutaneous connective tissue of the abdominal wall of 24 rats. Animals were sacrificed after 1 and 4 weeks resulting in eight specimen per group per time point. Specimen were subjected to histological evaluation (van Giesson's staining) and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA), fibronectin and tumour necrosis factor-alpha (TNF-α). RESULTS: Histological evaluation revealed dense scar formation at the titanium and H-NCD surfaces. In contrast, the connective tissue was loose at the O-NCD surface with a significantly higher number of cells after 4 weeks. O-NCD demonstrated a strong expression of PCNA and fibronectin but a weak expression of TNF-α. In contrast, the PCNA and fibronectin expression was low at the titanium and H-NCD, with a strong signal of TNF-α at the H-NCD surface. CONCLUSIONS: Hydrophilicity influences the connective tissue healing at polished implant surfaces in vivo positively. The attachment of connective tissue and the number of cells in contact to the surface were increased. Moreover, the inflammatory response is decreased at the hydrophilic surface.

Everolimus attenuates neointimal hyperplasia in cultured human saphenous vein grafts.

OBJECTIVE: Neointimal hyperplasia is the first step in a cascade leading to a reduced patency rate of saphenous vein grafts in comparison to arterial grafts in coronary artery bypass grafting. Using cultured human saphenous vein grafts as a model for coronary artery bypass grafting, we investigated if the mammalian target of rapamycin inhibitor everolimus attenuates neointimal hyperplasia. METHODS: Saphenous vein grafts from 10 patients undergoing coronary artery bypass grafting were processed as follows: from each patient, one segment served as baseline control at day 0. Two segments were cultured in a neointimal hyperplasia model separately. One received no treatment and the other everolimus (1 microM). All vein grafts underwent histomorphometric analysis, assessment of proliferation by Ki-67 immunostaining and quantification of phospho-S6 ribosomal protein using western blot analysis. RESULTS: Everolimus treatment resulted in reduced neointimal hyperplasia (thickness 3.7+/-1.2 microm) compared to untreated controls (10.1+/-2.5 microm, p=0.008). The intima/intima+media-ratio was reduced in the everolimus group (0.10+/-0.02) compared to untreated controls (0.24+/-0.07, p=0.008). The number of Ki-67 positive proliferating cells in everolimus treated vein grafts (15+/-7 cells/high power field) showed a tendency of reduction compared to untreated controls (36+/-20 cells/high power field, p=0.036). Finally, everolimus treatment resulted in downregulation of S6 ribosomal protein phosphorylation in comparison to untreated controls. CONCLUSION: Everolimus is able to reduce neointimal proliferation in cultured human saphenous vein grafts by inhibition of the mammalian target of rapamycin, even though different transfection methods are to be evaluated for a clinical application in coronary artery bypass grafting.