Biocompatibility studies

Biocompatibility is an essential property of new biomaterials for drug delivery. Biocompatibility is always assessed with respect to specific applications and may be assessed with respect to cytotoxicity, allergic responses, irritation, inflammation, mutagenicity, teratogenicity, and carcinogenicity (Katti el al., 2002). The reviews by Katti et al. (2002) and Domb et al. (1997) provide good discussions on the biocompatibility studies that have been conducted with polyanhydrides over the past two decades. 

See also Luminescent dendrimers antibacterial, 26 799 biocompatibility studies of, 26 800-801 in catalysis, 26 805-806 in cell targeting, 26 797-798 as chelators, 26 806-807 core and interior shells of, 26 789 cytotoxicity of, 26 800-801 in drug delivery, 26 792-795 in gene transfection, 26 791-792 as imaging agents, 26 795-797 luminescent, 26 801-804 medical applications of, 26 791-801 micelle-mimetic behavior of, 26 789 multiphoton applications of, 26 803-804... 

Lindner E, Cosofret V, Ufer S, Buck R, Kao W, Neuman M, Anderson J. Ion-selective membranes with low plasticizer content electroanalytical characterization and biocompatibility studies. Journal of Biomedical Materials Research 1994, 28, 591-601. 

Galeska I, Hickey T, Moussy F, Kreutzer D, Papadimitrakopoulos F. Characterization and biocompatibility studies of novel humic acids based films as membrane material for an implantable glucose sensor. Biomacromolecules 2001, 2, 1249-1255. 

The sensitivity to irritation is different for different tissues in the body. Biocompatibility is therefore highly related to the injection site. For instance, the rabbit eye is a highly sensitive animal model for biocompatibility studies [82, 83]. Surface topography is another important parameter of biocompatibility [79]. Sharp edges or corners may cause irritation and enhance the local tissue response [40]. 

Higa, O.Z. Rogero, S.O. Machado, L.D.B. Mathor, M.B. Lugao, A.B. Biocompatibility study for PVP wound dressing obtained in different conditions. Radiat Phys. Chem. 1999, 55, 705-707. 

Conclusions. Results from the biocompatibility studies in rabbit supratellar bursa, measurement of hydrophilic properties, lubrication and wear in-vitro studies, determination of viscoelastic properties, measurement of damping coefficient and impact test, total elbow joint replacement design and in-vivo percutaneous implant experiment, all indicate that this series of polyurethanes is an excellent candidate biomaterial for the prosthetic replacement of articular cartilage, artificial joint prostheses and percutaneous implantable devices. 

Rieger, W. (1993) Biocompatibility Studies on Zirconia and Alumina in Orthopaedic Joint Applications, Ascona, Switzerland. 

In the rabbit brain safety study using P(CPP-SA) 50 50 copolymer, even less of an inflammatory reaction was observed, and the polymer was essentially equivalent to Gelfoam [94]. In a similar brain biocompatibility study conducted in monkeys, no abnormalities were noted in the computer tomography scans and magnetic resonance images, nor in the blood chemistry or hematology evaluations [95]. No systemic effects of the implants were observed on histological examinations of any of the tissues tested [96]. No unexpected or untoward reactions to the treatments were observed. 

With these preclinical toxicology and biocompatibility studies carried out in animals having demonstrated both the efficacy and safety of the polyanhydrides, studies involving these materials moved toward human clinical use. In 1987, the Food and Drug Administration approved experimental use of these polyanhydrides in humans, under an Investigational New Drug clinical trial application. A Phase I/II clinical trial of 21 patients in five U.S. hospitals was carried out... 

Initial biocompatibility studies were conducted on polyanhydrides. As evaluated by mutation assays (29), the degradation products of the polymer were non-mutagenic and non-cytotoxic. Teratogenicity tests were also negative. Growth of mammalian cells in tissue culture was also not affected by these polymers (29). 

The use of an appropriate mammalian species for biocompatibility studies often has been a topic of heavy debate. The rationale for use of the dog in our system was based primarily on availability of subjects and cost. In addition, the adherence of dog platelets to cuprophane membranes was reported to be three orders of magnitude greater than the adherence of human platelets (41). The dog is also thought to have a highly potent fibrinolytic system (42). Thus, the dog should be a very sensitive animal for studying clot formation and dissolution. A clearer visualization of the mechanisms involved should therefore be possible. We believe that fundamental mechanisms underlie artificial surface-induced thrombosis and embolization in dogs, humans, and other mammalian species. 

Cadee JA, Brouwer LA, Den Otter W, Hennink WE, Van Luyn MJA. A comparative biocompatibility study of microspheres based on crosslinked dextran or poly(lactic-co-glycolic)acid... 

Sannino, A. Madaghiele, M. Lionetto, M.G. Schettino, T. Maffezzoli, A. A cellulose-based hydrogel as a potential bulking agent for hypocaloric diets An in vitro biocompatibility study on rat intestine. J. Appl. Polym. Sci. 2006,102 (2), 1524-1530. 

Silva A, Gonzalez-Mira E, Garcia M, Egea M, Fonseca J, Silva R et al. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SEN) High pressure homogenization versus ultrasound. Colloids and Surfaces B Biointerfaces. 2011 86(1) 158-165. 

M.V. Risbud, R.R. Bhonde, Suitability of cellulose molecular dialysis membrane for bioartificial pancreas in vitro biocompatibility studies, J. Biomed. Mater. Res. 54 (3) (2001) 436 44. 

Biocompatibility studies of the G5-glass, performed with human skin fibroblasts and osteoblast-Uke human cells from a cell fine coded MG63, have shown that this material as well as its degradation products are noncyto-toxic [22]. 

Bennett S, Connolly K, Lee DR, Jiang Y, Buck D, Hollinger JO, et al. Initial biocompatibility studies of a novel degradable polymeric bone substitute that hardens in situ. Bone 1996 19(1, Supplement) 101S-107S. 

The most common type of biocompatibility assay is the use of cell culture systems to identify cytotoxicity, cell adhesion, cell activation, or cell death. Cell culture assays are used extensively in biocompatibility studies of new biomaterials as well as being required in biocompatibility assessment programs for products, that is, biomaterials, medical devices, and prostheses (Table 2). 

Zhang, Z., R. Roy, F.J. Dugre, D. Tessier, and L.H. Dao. 2001. In vitro biocompatibility study of electrically conductivepolypyrrole-coated polyester fabrics. / Biomed Mater Res 57 63. 

The final results of these biocompatibility studies fiom the Oldaman report indicated that the AEM 5700/5772 Antimicrobial treated fidnic is noTKtoxic, non-irrit ing and nonsensitizing to human skin, and has a permanent antimicrobial crqpacity that caimot be extracted in use. These pre-clinical studies provide suffiderrt information to allow us to predict the biocompatihility of the finished products and siqtport their safe clinical use. As such, the treated fabric was considered safe fin- use in suigery. Yeats of clinical use with no untoward effects also support the suitability of the treated ric for its intended use. 

Marchant, R.E., Anderson, J.M. and Dillingham, E.O. (1986) In vivo biocompatibility studies. VII. Inflammatory response to polyethylene and to a cytotoxic polyvinylchloride. Journal of Biomedical Materials Research, 20, 37-50. 

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