Hyaluronan crosslinking

We prepared a phenol-containing hyaluronan derivative, which was inter-molecularly coupled by HRP to yield a crosslinked hydrogel (Scheme 27). The sequenhal injection of this hyaluronan derivative and peroxidase formed... 

In an attempt to mimic the physiological ratio of collagen type II to hyaluronan in the healthy human NP, Calderon et al. constructed hydrogels scaffolds composed of these two elements in a 9 1 (w/w) ratio [104]. Scaffolds were crosslinked with various concentrations of EDC/NHS, but it was found that 8 mM EDC/NHS resulted in a confined compressive modulus on the order of the native NP, while allowing for optimal rat mesenchymal stem cell (rMSC) viability and proliferation. Additionally, real time PCR results from rMSCs seeded on the scaffolds for 21 days indicated that the scaffolds promoted increased aggrecan expression and inhibited collagen type I expression compared to rMSCs cultured on monolayers. 

One such application could be delivery of Has2-pDNA, a plasmid that codes for hyaluronan synthase 2 [66]. This enzyme facilitates the synthesis of larger HA molecules and can prevent post-surgical peritoneal adhesions. In one study, DNA-HA films were prepared using previously-described chemistry however, lyophili-zation was replaced with air-drying under sterile conditions and an isopropanol/ H20 mixture was used instead of DMF/H20. The release kinetics of DNA were similar to that from the HA film described previously, but release did not occur until after 7 days. The reason for this delay was not completely clear the authors suggest that a possible way to overcome the delay is to use a crosslinked DNA-HA film sandwiched between two non-crosslinked DNA-HA films. Non-crosslinked film... 

Kim AP, Yellen P, Yun YH et al (2005) Delivery of a vector encoding mouse hyaluronan synthase 2 via a crosslinked hyaluronan film. Biomaterials 26 1585-1593... 

The physical or chemical crosslinking of polymers can be also realized in water-in-oil (W/O) emulsion systems. In this case, aqueous droplets of prepolymers are stabilized by oil-soluble surfactants in a continuous oil phase. Hyaluronan-based microgels were prepared by crosslinking of carboxylic units of hyaluronan with adipic dihydrazide in aqueous droplets [19]. Chitosan-based microgels were prepared by crosslinking of chitosan chains with glutaraldehyde in aqueous droplets [20-25],... 

Hyaluronan is used therapeutically to treat osteoarthritis in the knee, and is an effective treatment for arthritic pain. Crosslinked hyaluronan gels are used as drug delivery systems. 

Crescenzi V, Francescangeli A, Renier D, Bellini D. Hyaluronan linear and crosslinked derivatives as potential/actual biomaterials. In Kennedy JF, Phillips GO, Williams PA, Hascall VC, eds. Hyaluronan. Cambridge Wood-head Publishing, 2002 261-268. 

Liu YC, Li H, Shu XZ, Gray SD, Prestwich GD. Crosslinked hyaluronan hydrogels containing mitomycin C reduce postoperative abdominal adhesions. Fertil Steril 2005 83 1275-1283. 

Wang W. A novel hydrogel crosslinked hyaluronan with glycol chitosan. J Mater Sci Mater Med 2006 17 1259-1265. 

Masters, K. S., Shah, D. N., Leinwand, L. A., Anseth, K. S. Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells. Biomaterials. 2005, 26, 2517-2525. 

Hyaluronan haloacetate (HAHA) CMHA-S, TetraPAcs Tyramine crosslinked HA Click chemistry crosslinked HA Ugi condensation crosslinked HA... 

Liu Y, Shu X Z and Prestwich G D (2005b), Biocompatibility and stability of disulfide-crosslinked hyaluronan films , Biomaterials, 26, 4737-46. 

Skardal A, Zhang J and Prestwich G D (2010d), Bioprinting vessel-like constructs using hyaluronan hydrogels crosslinked with tetrahedral polyethylene glycol... 

Yang G, Espandar L, Mamahs N and Prestwich G D (2010), Accelerated repair of comeal epithehal abrasion and aUsah bum injuries in rabbits with a crosslinked hyaluronan derivative . Vet. Ophthalmology, 13, 144-50. 

Weng, L., Pan, H. Chen, W. 2008, Self-crosslinkable hydrogels composed of partially oxidized hyaluronan and gelatin in vitro and in vivo responses . Journal of... 

Skardal A, Zhang J, McCoard L, Oottamasathien S, Prestwich GD. Dynamically crosslinked gold nanoparticle—hyaluronan hydrogels. Adv Mater. 2010 22 4736-40. 

V. Dulong, S. Lack, D. Le Cerf, L. Picton, J. Vannier, and G. Muller, Hyaluronan-based hydrogels particles prepared by crosslinking with trisodium trimetaphosphate. Synthesis and characterization, Carbohydr. Polym., 57 (1), 1-6, 2004. 

In a departure from historical approaches to introducing fillers in UHMWPE, researchers from Colorado State University have developed a novel UHMWPE-hyaluronan microcomposite [50, 51]. This microcomposite is detailed in Chapter 18. Hyaluronan is a natural lubricant in articular cartilage. By incorporating this biomolecule into UHMWPE, researchers theorized that wear could be reduced. Because hyaluronan is hydrophilic and UHMWPE is hydrophobic, fabrication of an UHMWPE-hyaluronan microcomposite is by no means a straightforward proposition and is accomplished via a complex and elegant multistep procedure. The process, which is described in greater detail in Chapter 18, begins with the production of a porous UHMWPE substrate, which constitutes the matrix of the microcomposite. The hyaluronan is complexed with quaternary ammonium cations (CTA-I-) and silylated [52]. A solution of silyl hyaluronan-CTA is then diffused into the open celled porous UHMWPE matrix, chemically crosslinked in situ, and then hydrolyzed... 

Other chapters in this Handbook detail the various conventional and crosslinked UHMWPE materials that have been used in joint replacement implants since the 1960s. While UHMWPE articulating against a metalhc component remains the gold standard for joint replacements, researchers continue to develop modified and improved UHMWPE materials. One such material, BioPoly , a microcomposite of UHMWPE and hyaluronan (HA) was developed by Professor Sue James and colleagues at Colorado State University. UHMWPE/HA biomaterials are considered microcomposites because a small amount (<5%) of HA is covalently locked into a porous... 

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