Pro-angiogenic and osteogenic composite scaffolds of fibrin, alginate and calcium phosphate for bone tissue engineering

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation.

Nature-inspired remodeling of (aza)indoles to meta-aminoaryl nicotinates for late-stage conjugation of vitamin B3 to (hetero)arylamines

Despite the availability of numerous routes to substituted nicotinates based on the Bohlmann–Rahtz pyridine synthesis, the existing methods have several limitations, such as the inevitable ortho-substitutions and the inability to conjugate vitamin B3 to other pharmaceutical agents. Inspired by the biosynthesis of nicotinic acid (a form of vitamin B3) from tryptophan, we herein report the development of a strategy for the synthesis of meta-aminoaryl nicotinates from 3-formyl(aza)indoles. Our strategy is mechanistically different from the reported routes and involves the transformation of (aza)indole scaffolds into substituted meta-aminobiaryl scaffolds via Aldol-type addition and intramolecular cyclization followed by C–N bond cleavage and re-aromatization. Unlike previous synthetic routes, this biomimetic method utilizes propiolates as enamine precursors and thus allows access to ortho-unsubstituted nicotinates. In addition, the synthetic feasibility toward the halo-/boronic ester-substituted aminobiaryls clearly differentiates the present strategy from other cross-coupling strategies. Most importantly, our method enables the late-stage conjugation of bioactive (hetero)arylamines with nicotinates and nicotinamides and allows access to the previously unexplored chemical space for biomedical research.

Clinical-statistical Study on the Biomimetic Adhesion of Whole Ceramic Inlays

Currently, a new approach to restorative dentistry is possible, from biomimetic point of view, by using restorative materials with a natural tooth-like structure and very strong adhesion to the hard remaining tissues. The objective of the study was to compare in vitro the marginal adaptation of restorations with whole ceramic inlays, using the biomimetic method compared to the classical method. A batch of 60 extracted impacted molars was used for the study. Large cavities were prepared at occlusal proximal surfaces according to minimally invasive therapy principles. The teeth were divided into 4 study groups (A, B, C, D). Batches A and C contain teeth prepared and restored through classical method, with entirely ceramic inlays. Batches B and D contain teeth restored through biomimetic adhesive method. After preparation, fluid composite (Gradia Direct Flo - GC) was used as a basic filling material to seal dentine wounds and dental canaliculi according to biomimetic principles. Cementing was done with Variolink Esthetic DC-Ivoclar (lot A and B) and with Maxcem Elite - Kerr (lot C and D). Samples were cut and prepared for microscopic analysis. The analysis of the four batches revealed the existence of the microfissure in the dentine wounds and the presence of fragments detached from the cementing material layer. The hybrid layer is homogeneous with qualitative dental canaliculi sealing. The difference between the two methods is the size of these defects, in the case of the classical method being approximately 2 times larger. The difference between the two types of cementing material used is due to the fact that in case of Maxcem Elite - Kerr cement, discontinuities have been observed at the level of cementing material - inlay material interface. The biomimetic method is superior to the classical one, the integrity of the layers of materials used in the biomimetic treatment is clearly superior to the integrity of the layers of material used in the classical treatment.

Construction of novel temperature-responsive hydrogel culture system based on the biomimetic method for stem cell sheet harvest

Temperature-responsive hydrogel culture system is considered as an ideal platform for cell sheet harvest, but its complex preparation methods and harsh reaction conditions limit its application. Inspired by the marine mussels, a biomimetic method presented here is to construct a novel temperature-responsive hydrogel culture system for stem cell sheet harvest. The tissue culture polystyrene is first modified with polydopamine coating, and then amine-terminated poly(N-isopropylacrylamide) is grafted onto the coating via the Schiff base or Michael addition reaction to construct the temperature-sensitive hydrogel culture system. Then, bone marrow stromal cells are cultured on the culture system to construct cell sheets. The prepared culture system shows significant temperature-sensitive property with the grafted concentrations of poly(N-isopropylacrylamide) ranging from 0.5 to 1 g/L. Meanwhile, the constructed culture system has low cytotoxicity and facilitates the stem cell adhesion, proliferation, and cell sheet formation at 37°C. When the culture system is placed in a 20°C environment, the cell sheet can be completely detached from the surface of tissue culture polystyrene without being treated with any enzymes. More importantly, the cell morphology, cell sheet thickness, and the fibril structure of the associated proteins are similar to the cells cultured on the tissue culture polystyrene without modification. The biomimetic, simple, inexpensive, and environmentally friendly preparation of the culture system enables it to be used for the harvest of cell sheet and even applied to tissue engineering for tissue regeneration.