Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates) and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.
Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological angiogenesis and those of angiogenesis activation and inhibition. In healthy adults, angiogenesis is absent apart from its involvement in female reproductive functions and tissue regeneration. Angiogenesis is a complex process regulated by the action of specific activators and inhibitors. In certain diseases, modulating the angiogenic balance can be a therapeutic route, either by inhibiting angiogenesis (for example in the case of tumor angiogenesis), or by trying to activate the process of new blood vessels formation, which is the goal in case of cardiac or peripheral ischemia.
Bone regeneration in critical-size defects requires biomaterials that provide both structural support and appropriate osteoinductive cues. Natural nacre contains an organic matrix rich in acidic macromolecules with reported osteogenic activity; however, its in vivo regenerative potential remains insufficiently explored. This study evaluated the bone regenerative capacity of nacre-derived materials alone and combined with oxidized porous silicon microparticles (pSi-MP), a bioactive material known to release silicic acid and support mineralized tissue formation. Critical-size defects were created in four caudal vertebrae of Wistar rats and filled with nacre, pSi-MP, a nacre–pSi composite, or left empty. After 60 days, bone formation was assessed using micro-computed tomography and non-decalcified histology. Empty defects failed to regenerate, whereas nacre and pSi-MP individually promoted partial mineralized tissue deposition. The nacre–pSi composite produced the most extensive repair, showing near-complete defect bridging, higher bone mineral density, and seamless integration of particles within newly formed bone. No inflammation or adverse reactions were observed, and osteoid deposition occurred directly on material surfaces. These findings demonstrate that nacre-derived materials exert intrinsic osteogenic effects in vivo and that combining nacre with porous silicon yields a synergistic response that significantly enhances bone regeneration. The composite represents a promising candidate for future bone repair strategies.