In the present study, we explored the binding capacity of synthetic heparin-like dextran derivatives to recombinant human bone morphogenetic protein 2 (BMP-2), a heparin-binding osteoinductive growth factor. Affinity electrophoresis analysis provided evidence that carboxymethylated dextran polymers grafted with high amounts of benzylamide groups (named DMCB) interact with BMP-2. The capability of such polysaccharides to potentiate the growth factor biological activity was then investigated. In vitro, DMCB dose-dependently promoted osteoblast differentiation induced by BMP-2 in C2C12 myoblasts more efficiently than heparin. A screening study provided evidence that the potentiating effects of the dextran derivatives on the BMP-2-induced alkaline phosphatase activity improved with their benzylamide groups content and, therefore, with their affinity for the growth factor. The biological activity of BMP-2 was monitored in the culture medium after 6 days using C2C12 cells (containing a BMP sensitive luciferase reporter gene). Like heparin, DMCB sustained the biological activity of the growth factor; this result suggests that the formation of the BMP-2/DMCB complex may protect the protein from being inactivated. In rats in vivo, DMCB also stimulated ectopic calcification mediated by BMP-2. These data indicate that dextran-based polysaccharides prolong the half-life of the growth factor and promote its biological activity.

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Polysaccharide microarrays have great potential for the high-throughput analysis of polysaccharide-protein interactions. Here we demonstrate that a polysaccharide microarray prepared by printing a library of dextran polymers derivatized by methylcarboxylate, benzylamide, and sulfate groups (DMCBSu compounds) on to glass slides permitted the rapid identification of a set of compounds able to interact with the platelet-derived growth factor BB (PDGF-BB) isoform, a growth factor involved in wound healing. Microarray interaction results were compared to the capacity of DMCBSu compounds to potentiate the in vitro PDGF-BB-induced proliferation of human dermal fibroblasts.

Highly porous dextran-based hydrogels [in which various amounts (up to 16.6%, w/w) of a benzylaminated dextran (DMCB) exhibiting high affinity for TGFbeta1 was immobilized] were developed to achieve long-term retention of bioactive TGFbeta1 in situ. Unmodified hydrogels rapidly desorbed 80-90% compared with only 40-60% of the preloaded TGFbeta1 from the DMCB-modified hydrogels during a period of 21 days in PBS in vitro. TGFbeta1 release experiments (performed with high ionic strength solutions) indicated that formation of the complex between TGFbeta1 and functionalized hydrogels was governed by different interactions, depending on the degree of conjugation with DMCB: ionic interactions in the case of weakly conjugated matrices and nonionic interactions in highly conjugated matrices. Using cells containing a TGFbeta-sensitive luciferase reporter gene, weakly DMCB-modified hydrogels sequestered bioactive TGFbeta1 in situ, giving much higher, long-term signaling performance than highly functionalized hydrogels. Because these biocompatible functionalized hydrogels can provide long-term bioactive TGFbeta1, they could be used as scaffolds for cells to stimulate and regulate human tissue repair processes.

Monolayer graphene directly presented on the wound bed is assessed for its healing properties using both in vitro and in vivo models. For in vivo study, a cutaneous excisional wound is created on the dorsal surface of healthy and type-1 diabetic mice to mimic acute and delayed wound healing, respectively. A pig model is also chosen for its resemblance to human skin. Photographic and histological assessment of the wound are coupled with thermographic data recorded with an infrared camera. Graphene monolayer accelerates early phases of wound healing in vivo in every tested model. Upon removal of the bandage, wounds coated with graphene are less prone to temperature drop compared to the control samples. We hypothesize that graphene may directly shorten the inflammatory phase and/or enhance angiogenesis and cell migration in proliferative phase as demonstrated in vitro. Thermographic assessment of wounds could be of particular interest to follow both phenomena in an objective, rapid and non-invasive manner.