The presence of micropores in calcium phosphate (CaP) ceramics has shown its important role in initiating inductive bone formation in ectopic sites. To investigate how microporous CaP ceramics trigger osteoinduction, we optimized two biphasic CaP ceramics (i.e., BCP-R and BCP-S) to have the same chemical composition, equivalent surface area per volume, comparable protein adsorption, similar ion (i.e., calcium and phosphate) exchange and the same surface mineralization potential, but different surface architecture. In particular, BCP-R had a surface roughness (Ra) of 325.4 ± 58.9 nm while for BCP-S it was 231.6 ± 35.7 nm. Ceramic blocks with crossing or noncrossing channels of 250, 500, 1000, and 2000 µm were implanted in paraspinal muscle of dogs for 12 weeks. The percentage of bone volume in the channels was not affected by the type of pores (i.e., crossing vs. closed) or their size, but it was greatly influenced by the ceramic type (i.e., BCP-R vs. BCP-S). Significantly, more bone was formed in the channels of BCP-R than in those of BCP-S. Since the two CaP ceramics differed only in their surface architecture, the results hereby demonstrate that microporous CaP ceramics may induce ectopic osteogenesis through surface architecture.

Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and should therefore be adjustable. In this study a new type of heparin release system is presented which may be applied as a coating for blood contacting devices. The system is based on the covalent immobilization of heparin onto porous structures via hydrolysable bonds. This approach was evaluated by the immobilization of heparin onto a porous cellulosic substrate via ester bonds. Cuprophan was used as a model substrate and N,N'-carbonyldiimidazole as a coupling agent. Heparinized Cuprophan incubated in phosphate buffered saline showed a release of heparin due to the hydrolysis of the ester bonds between heparin and Cuprophan. The release rate could be easily adjusted by varying the amount of coupling agent used during immobilization. Cuprophan with a rather stable heparin coating (release rate: 6.1 mU/cm2'h) and Cuprophan which shows a substantial release of heparin (release rate up to 23.0 mU/cm2.h) could be prepared. Except when the release was relatively high, release rates were constant for at least 1 week. Storage of the release system at ambient conditions up to 6 months or sterilization by means of steam, ethylene oxide exposure, or gamma irradiation did not affect the release properties. It was concluded that this concept for a heparin release system is highly promising to prepare thromboresistant surfaces for various blood contacting devices.

Cuprophan hemodialysis membranes can be heparinized using N,NЈ-carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics of heparinized Cuprophan membranes have been evaluated. After immobilization, heparin partially retained its biologic activity. An anticoagulant activity of 12.4 ± 4.2 mU/cm 2 was measured using a thrombin inactivation assay. Immobilized heparin also displayed an anti-complement activity. After contact with human serum, heparinized Cuprophan induced no generation of significant amounts of fluid phase terminal complement complex (TCC), whereas untreated Cuprophan induced the generation of substantial amounts of TCC. Heparinization did not affect the permeability of Cuprophan for model solutes with molecular weights up to 12,000 g/mol except for sulfobromophthalein sodium salt. The permeability of Cupro-phan for sulfobromophthalein sodium salt was slightly decreased after heparinization. The ultrafiltration rate of Cuprophan increased by about 30% after heparinization, probably owing to an increased swelling of the membrane in water. Heparinized Cuprophan incubated in phosphatebuffered saline at 37°C showed some release of heparin. These amounts of released heparin, however, were very low as compared to the amounts of heparin which are systemically administered during clinical hemodialysis treatment. It is concluded that Cuprophan membranes heparinized by means of the CDI-activation procedure are highly promising for application in hemodialyzers to be used for the treatment of patients with reduced or without systemic administration of heparin.

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