**5. Dextran and its derivatives**

**Figure 2.** Light-microscope evaluation of the tissue response to collagen sponges with hamatoxylin-eosin (HE) stain‐ ing: (A) 1 week after implantation; (B) 2 weeks after implantation; (C) 4 weeks after implantation; (D) 6 weeks after implantation; (E) 8 weeks after implantation. The scale bar indicates a distance of 50μm in (A), (C), and (D), and a

Combination of gelatin microspheres/scaffolds with other biomaterials, such as collagen, al‐ ginate, chitosan, hyaluronan, and fibrin has also been explored extensively. For example, a gelatin microsphere containing basic fibroblast growth factor and preadipocytes, is essential to achieve a engineered fat tissue [26]. A PLGA microparticles containing an anticancer agent paclitaxel was formulated for the treatment of lung cancers [27]. Gelatin hydrogel in‐ corporating hepatocyte growth factor induced angiogenic change around the implanted hy‐

25μm in (B) and (E) [13].

116 Advances in Biomaterials Science and Biomedical Applications

Dextran, a high-molecular-weight polymer of d-glucose, formed by sucrose enzymes on the cell surface of certain lactic acid bacteria in the mouth adhere to the tooth surfaces and pro‐ duce dental plaque. Uniform molecular weight dextrans (named for their average molecular weight) from Leuconostoc mesenteroides with specific preparations has been used for over 50 years in plasma volume expansion, thrombosis prophylaxis, peripheral blood flow en‐ hancement and for the rheological improvement of, for instance, artificial tears [30,58]. Dex‐ trans with an average molecular weight of 1000 to 2 million g/mol are commercially available for research purposes [59]. Two preparations of dextran with lower fractions (40000 and 70000 g/mol) are suitable for nontoxic clinical use [60]. However, high fractions of dextrans can produce erythrocyte aggregation, impaired microcirculation, and a clinical picture akin to shock and certain other diseases.

**Figure 3.** Eleven-day Masson's trichrome (MT) staining sections of a fibrin scaffold. (A) Untreated defects and (B) de‐ fects containing empty scaffolds were filled with new bone tissue. However, no reparative bone was observed in the center of defects containing (C) scaffolds filled with fibrin (low T) and (D) scaffolds filled with fibrin (high T). (Inset) Patches of multinucleated giant cells (striped arrow) were observed at the scaffold interface in all scaffold-containing groups. Black arrows point to areas occupied by the scaffold, whereas white arrows point to the advancing bone front. Field width 5.2 mm, inset field width 0.2 mm [46].

During 1990-1994, extensive toxicologic evaluations indicate that small-volume infusions of 7.5% NaCl/6% dextran 70 (HSD) at the proposed therapeutic dose of 4 mL/kg, present little risk as implantable biomaterials [61,62]. Dextran hydrogels have offered good opportunities as protein delivery systems or tissue engineering scaffolds because of an inherent biocom‐ patibility [63]. The hydrophilic, soft and rubbery properties of the dextran hydrogels ensure minimal tissue irritation and a low tendency of cells and proteins to adhere to the hydrogel surface [59]. Althogh dextran itself is not toxic, some of the methods used for crosslinking the polymer may result in toxic byproducts. For example, the toxicity of dialdehyde cross‐ linked dextran/gelatin hydrogel can be detected in fibroblast and endothelial cell cultures. Subcutaneous implantation studies in mice showed that the foreign body reaction seen around the implanted hydrogel samples was moderate and became minimal upon increas‐ ing implantation time [64]. A methacrylate-derivatized dextran hydrogel also shows good *in vitro* biocompatibilities [65].

More recently another effect of dextran, namely that of antithrombogenesis, has been recog‐ nized [66]. Dextran sulfate, a dextran derivative, its effects on coagulation has already been proven [67]. It has been reported that dextran sulfate has been found to activate the poly‐ merization of fibrin monomer, ATIII, conversion of prekallikrein to kallikreinand fibrinoly‐ sis. Kallikrein, the conversion of fibrinogen to fibrin appears to be inhibited by dextran sulfate. These effects are, *inter alia*, concentration dependent [67,68]. Meanwhile, a dextran sulphate sodium model of colitis has demonstrated several correlations of this biomaterial with human inflammatory bowel disease [69]. Furthermore, a lauric acid modified dextranagmatine bioconjugate (Dex-L-Agm) was prepared by 1,1'-carbonyldiimidazole activation and the nucleophilic reaction between tosyl of tosylated dextran and primary amine of ag‐ matine was found to be highly cytocompatible without causing hemolysis and red blood cell aggregation [70].
