Dietary phosphorus (P) is essential for bone mineralisation in vertebrates. P deficiency can cause growth retardation, osteomalacia and bone deformities, both in teleosts and in mammals. Conversely, excess P supply can trigger soft tissue calcification and bone hypermineralisation. This study uses a wide range of complementary techniques (X-rays, histology, TEM, synchrotron X-ray tomographic microscopy, nanoindentation) to describe in detail the effects of dietary P on the zebrafish skeleton, after two months of administering three different diets: 0.5% (low P, LP), 1.0% (regular P, RP), and 1.5% (high P, HP) total P content. LP zebrafish display growth retardation and hypomineralised bones, albeit without deformities. LP zebrafish increase production of non-mineralised bone matrix, and osteoblasts have enlarged endoplasmic reticulum cisternae, indicative for increased collagen synthesis. The HP diet promotes growth, high mineralisation, and stiffness but causes vertebral centra fusions. Structure and arrangement of bone matrix collagen fibres are not influenced by dietary P in all three groups. In conclusion, low dietary P content stimulates the formation of non-mineralised bone without inducing malformations. This indicates that bone formation and mineralisation are uncoupled. In contrast, high dietary P content promotes mineralisation and vertebral body fusions. This new zebrafish model is a useful tool to understand the mechanisms underlying osteomalacia and abnormal mineralisation, due to underlying variations in dietary P levels.

Temporomandibular joint osteoarthritis (TMJ-OA) is a chronic degenerative disease that is often characterized by progressive impairment of the temporomandibular functional unit. The aim of this randomized controlled animal trial was a comparative analysis regarding the chondroregenerative potency of intra-articular stem/stromal cell therapy. Four weeks after combined mechanical and biochemical osteoarthritis induction in 28 rabbits, therapy was initiated by a single intra-articular injection, randomized into the following groups: Group 1: AB Serum (ABS); Group 2: Hyaluronic acid (HA); Group 3: Mesenchymal stromal cells (STx.); Group 4: Mesenchymal stromal cells in hyaluronic acid (HA + STx.). After another 4 weeks, the animals were euthanized, followed by histological examination of the removed joints. The histological analysis showed a significant increase in cartilage thickness in the stromal cell treated groups (HA + STx. vs. ABS, p = 0.028; HA + ST.x vs. HA, p = 0.042; STx. vs. ABS, p = 0.036). Scanning electron microscopy detected a similar heterogeneity of mineralization and tissue porosity in the subchondral zone in all groups. The single intra-articular injection of a stem cell containing, GMP-compliant advanced therapy medicinal product for the treatment of iatrogen induced osteoarthritis of the temporomandibular joint shows a chondroregenerative effect.

For the post-surgical treatment of oral wounds and mucosal defects beyond a certain size, the gold standard is still an autologous skin or mucosal graft in combination with complex suturing techniques. A variety of techniques and biomaterials has been developed for sutureless wound closure including different tissue glues or collagen patches. However, no wound covering that enables for sutureless fixation has yet been introduced. Thus, a new system was developed that allows for sutureless wound covering including a transparent collagen membrane, which can be attached to the mucosa using a specially modified 2λ laser beam with integrated temperature sensors and serum albumin as bio-adhesive. The sutureless wound closure system was tested for its applicability and its cytocompatibility by an established in vitro model in the present study. The feasibility of the laser system was tested ex vivo on a porcine palate. The in vitro cytocompatibility tests excluded the potential release of toxic substances from the laser-irradiated collagen membrane and the bio-adhesive. The results of the ex vivo feasibility study using a porcine palate revealed satisfactory mean tensile strength of 1.2–1.5 N for the bonding of the membrane to the tissue fixed with laser of 980 nm. The results suggest that our newly developed laser-assisted wound closure system is a feasible approach and could be a first step on the way towards a laser based sutureless clinical application in tissue repair and oral surgery.

Advanced glycation end products (AGEs) accumulate in various tissues, including bone, due to aging and conditions like diabetes mellitus. To investigate the effects of AGEs on bone material quality and biomechanical properties, an in vitro study utilizing human tibial cortex, sectioned into 90 beams, and randomly assigned to three mechanical test groups was performed. Each test group included ribose (c = 0.6 M) treatment at 7-, 14-, and 21-d, alongside control groups (n = 5 per group). Fluorescent AGE (fAGE) and carboxymethyl-lysine (CML) levels were assessed through fluorometric analysis and mass spectrometry, while bone matrix composition was characterized using Fourier-transform infrared and Raman spectroscopy. Mechanical properties were determined through nanoindentation and three-point bending tests on non-notched and notched specimens. The results showed significant increases in fAGEs levels at 7-, 14-, and 21-d compared to controls (119%, 311%, 404%; p = .008, p < .0001, p < .0001, respectively), CML levels also rose substantially compared to controls (383%, 503%, 647%, p < .0001, p < .0001, p < .0001, respectively). Analysis of bone matrix composition showed greater sugars/Amide I ratio at 21-d glycation compared to controls, 7-d, and 14-d (p = .001, .011, .006, respectively); and higher carbonate-to-phosphate ratios in the ribose treatment group compared with controls (p < .05) in the interstitial bone area. Mechanical testing of notched specimens exhibited a higher yield force, pre-yield toughness, and maximum force at 14-d glycation compared to controls and to both 7-d and 21-d glycation (p < .05). Nanoindentation showed that the hardness was lower at 7-d glycation compared to the controls and 21-d glycation (p < .05). In conclusion, the study found altered mechanical properties at 7 and 14 d of glycation, which then returned to control levels at 21 d, indicating a dynamic relationship between glycation duration and mechanical characteristics that deserves further exploration.