W. E. G. Müller’s research while affiliated with Johannes Gutenberg University Mainz and other places

Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks ( p = 0.029), and between the former and autogenous bone at six weeks ( p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT ( r =−0.101, 95% CI [−0.445; 0.268]) or histology ( r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

Objective Bone grafting is an important surgical procedure to restore missing bone in patients with alveolar cleft lip/palate, aiming to stabilize either sides of the maxillary segments by inducing new bone formation, and in bilateral cleft cases also to stabilize the pre-maxilla. Polyphosphate (PolyP), a physiological polymer composed of orthophosphate units linked together with high-energy phosphate bonds, is a naturally existing compound in platelets which, when complexed with calcium as Ca-polyP microparticles (Ca-polyP MPs), was proven to have osteoinductive properties in preclinical studies. Aim To evaluate the feasibility, safety, and osteoinductivity of Ca-polyP MPs as a bone-inducing graft material in humans. Methods This prospective non-blinded first-in-man clinical pilot study shall consist of 8 alveolar cleft patients of 13 years or older to evaluate the feasibility and safety of Ca-PolyP MPs as a bone-inducing graft material. Patients will receive Ca-polyP graft material only or Ca-polyP in combination with biphasic calcium phosphate (BCP) as a bone substitute carrier. During the trial, the participants will be investigated closely for safety parameters using radiographic imaging, regular blood tests, and physical examinations. After 6 months, a hollow drill will be used to prepare the implantation site to obtain a biopsy. The radiographic imaging will be used for clinical evaluation; the biopsy will be processed for histological/histomorphometric evaluation of bone formation. Discussion This is the first-in-man study evaluating the safety and feasibility of the polyP as well as the potential regenerative capacity of polyP using an alveolar cleft model. Trial registration Indonesian Trial Registry INA-EW74C1N . Registered on 12 June 2020

Silicon is a keystone nutrient in the ocean for understanding climate change because of the importance of Southern Ocean diatoms in taking up CO2 from the surface ocean–atmosphere system and sequestering carbon into the deep sea. Here we report on silicon isotopes and germanium-to-silicon ratios in giant glass spicules of deep-sea sponge Monorhaphis chuni over the past 17,000 years. In-situ measurements of Si isotopes and Ge concentrations show systematic variations from rim to center of the cross sections. When calibrated against seawater concentrations using data from modern spicule rims, sponge data indicate that dissolved silica concentrations in the deep Pacific were ~12 % higher during the early deglacial. These deep Pacific Ocean data help to fill an important global gap in paleo-nutrient records. Either continental sources supplied more silica to the deglacial ocean and/or biogenic silica burial was lower, both of which may have affected atmospheric CO2.

Structural biomaterials are hierarchically organized and biofabricated. Biosilica represents the main mineral component of the sponge skeletal elements/spicules. We summarize recent data on the different levels of molecular, biological, and structural hierarchies controlling the synthesis of the picturesquely and intricately architectured spicules/skeletons.Biosilica is a promising material/substance for the amelioration and/or treatment of human bone diseases and dysfunctions. It has been demonstrated that biosilica causes in vitro a differential effect on the expression of the genes OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of NF-κB), as well as induces the expression of the key mediator BMP-2 (bone morphogenetic protein 2), they are promising candidates for treatment of osteoporosis.

Sponges are among the earliest diverging crown-group animals and widely regarded as the earliest biomineralizing animals. Indeed, unambiguous hexactine sponge spicules first occur in the lowermost Cambrian strata of the Fortunian Stage. Articulated sponge skeletons interpreted as hexactinellids and demosponges have been reported from Cambrian Stage 2-3 strata at multiple localities. Articulated sponge skeletons in the Chengjiang biota (Cambrian Stage 3), however, are dominated by forms interpreted as demosponges, despite the exceptional preservation in this biota. Here, we report new articulated sponge skeletons from the Chengjiang biota, including Paradiagoniella magna n. gen. n. sp. and P. xiaolantianensis n. gen. n. sp. The skeleton of both species consists of ranked stauractines and rare oxeas (straight or curved diactines), as well as hexactines in the former species. Their stauractines form irregular, nested, local sub-quadrules oriented obliquely to the sponge body axis. Sub-quadrules of different ranks are not in parallel arrangement. The two species are tentatively placed in the family Protospongiidae, which as currently defined may be a paraphyletic group including members of the total-group hexactinellids and perhaps stem-group siliceans. The phylogenetic placement of P. magna and P. xiaolantianensis is uncertain but, like many other protospongiids, they could be members of the total-group hexactinellids or stem-group siliceans. The diactines in the two species could be secondarily reduced hexactine-based spicules; alternatively, these two species may represent an evolutionary grade of stem-group siliceans with both diactines and hexactine-based spicules, the latter of which was lost in demosponges. A comprehensive cladistics analysis is needed to resolve the exact phylogenetic placement of the two species described here.

Inspired by the intermolecular cross-linking of mussel foot proteins and their adhesive properties, tyrosinase has been used to modify recombinant silicatein. DOPA/DOPAquinone-mediated cross-linking and interfacial interactions enhanced both self-assembly of silicatein building blocks and templating of core–shell silica spheres, resulting in fluorescent biomimetic silicatein–silica hybrid mesofibers.

(+/-)-Aeroplysinin-1, an optically active 1,2-dihydroarene-1,2-diol, was isolated from the marine sponges Verongia aerophoba (+-isomer) and Ianthella ardis (- -isomer). For the experiments presented we used the +-isomer from Verongia aerophoba. Here we describe the hitherto unknown biological and pharmacological property of this compound to display pronounced anticancer activity against L5178y mouse lymphoma cells (ED50: 0.5 microM). Friend erythroleukemia cells (ED50: 0.7 microM), human mamma carcinoma cells (ED50: 0.3 microM) and human colon carcinoma cells (ED50: 3.0 microM) in vitro. Furthermore, aeroplysinin caused a preferential inhibition of [3H]thymidine (dThd) incorporation rates in L5178y mouse lymphoma cells if compared with murine spleen lymphocytes in vitro. At concentrations between 1.1 and 28.5 microM, the [3H]dThd incorporation rates in L5178y cells were suppressed to 28%-0% but only to 78%-18% in murine spleen lymphocytes. The same differential effect in vitro was found with the following epithelial cells: 14.70 microM of the compound were required to inhibit normal human fibroblasts to 50%, but only 2.9 microM in the assays with human malign keratinocytes or malignant melanoma cells to observe the same inhibitory effect. Moreover, aeroplysinin-1 displayed antileukemic activity in vivo using the L5178y cell/NMRI mouse system; administered at a dose of 50 mg/kg for five consecutive days, the T/C (%) value was determined to be 338. Preliminary toxicology studies revealed an acute LD50 of 202 mg/kg and a subacute LD50 of 150 mg/kg. Aeroplysinin-1 is neither a direct mutagen nor a premutagen in the umu/Salmonella typhimurium test system.

Analysis of the tropical marine sponge Axinella carteri afforded six unusual alkaloids, including the new brominated guanidine derivative 3-bromo-hymenialdisine. The structure elucidation of the new alkaloid is described. The alkaloid patterns of sponges collected in Indonesia or in the Philippines were shown to be qualitatively identical suggesting de novo synthesis by the sponge or by endosymbiontic microorganisms rather than uptake by filter feeding. All alkaloids were screened for insecticidal activity as well as for cytotoxicity. The guanidine alkaloids hymenialdisine and debromohymenialdisine exhibited insecticidal activity towards neonate larvae of the polyphagous pest insect Spodoptera littoralis (LD50s of 88 and 125 ppm, respectively), when incorporated into artificial diet and offered to the larvae in a chronic feeding bioassay. The remaining alkaloids, including the new compound were inactive in this bioassay. Cytotoxicity was studied in vitro using L5178y mouse lymphoma cells. Debromohymenialdisine was again the most active compound (ED50 1.8 micrograms/ml) followed by hymenialdisine and 3-bromohymenialdisine, which were essentially equitoxic and exhibited ED50s of 3.9 micrograms/ml in both cases. The remaining alkaloids were inactive against this cell line.