Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors are heparin-binding proteins (HBPs) that have a high affinity for cell surface heparan sulfate proteoglycans (HSPG). In the present study, we report the binding kinetics and affinity of heparin interacting with different growth factors, including fibroblast growth factor (FGF) 2,7,10, hepatocyte growth factor (HGF) and transforming growth factor (TGF β-1), using a heparin chip. Surface plasmon resonance studies revealed that all the tested growth factors bind to heparin with high affinity (with K_D ranging from ~0.1 to 59 nM) and all the interactions are oligosaccharide size dependent except those involving TGF β-1. These heparin-binding growth factors also interact with other glycosaminoglycans (GAGs), as well as various chemically modified heparins. Other GAGs, including heparan sulfate, chondroitin sulfates A, B, C, D, E and keratan sulfate, showed different inhibition activities for the growth factor-heparin interactions. FGF2, FGF7, FGF10 and HGF bind heparin but the 2-O-sulfo and 6-O-sulfo groups on heparin have less impact on these interactions than do the N-sulfo groups. All the three sulfo groups (N-, 2-O and 6-O) on heparin are important for TGFβ-1-heparin interaction.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Carboxymethyl-chitosan, a water-soluble derivative of chitosan, has emerged as a promising candidate for biomedical applications due to its excellent water solubility, biodegradation, biocompatibility, hydrating, antimicrobial, and nontoxicity. In this paper, the antitumor proliferation and metastasis was studied in vitro and in vivo to evaluate biocompatibility of carboxymethyl-chitosan as biomaterials for antitumor drug delivery. The results showed that carboxymethyl-chitosan could significantly reduce the clone formation and tumor migration of human cancer cells including kidney cancer cell line OS-RC-2, gastric cancer cell line SGC-7901, colon cancer cell line HT-29, and nonsmall cell lung cancer cell line NCI-H1650 in vitro. Through Lewis tumor-bearing C57BL/6 mouse model, carboxymethyl-chitosan was proved to be able to inhibit solid tumor growth and tumor metastasis to the liver and lung, meanwhile increase the level of tissue inhibitor of metalloproteinase 1 and E-cadherin, and decrease the level of mice blood serum matrix metalloproteinase 9. This study suggested that carboxymethyl-chitosan had certain antimetastasis effect and good biocompatibility and may have a potential application as a synergic antitumor reagent.