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Biomedical subjects

A Renken

Publications and source records attributed to A Renken.

4 recordsLinked to original sources

Objectively assessing bioartificial organs.

The metrics used, thus far, to assess bioartificial organ function are shown to be subjective and requiring validation. Therefore, four categories of correlations are proposed based on, respectively, device, in vitro and in vivo evaluations, and clinical function. Examples are presented whereby the correlations among individual indicators are used as a means to expedite the development of immunoisolated cells. Specifically, a case study illustrating the validation of in vitro indicators of in vivo graft function for the bioartificial pancreas (microencapsulated islets) is summarized. This has revealed thresholds with respect to given metrics relating to in vivo device function, the necessity to couple bioartificial organ design with transplant site selection, as well as the lack of objectivity involved in the evaluation and establishment of hypotheses. Specific quantitative indicators illustrate the need for quality-controlled measures, for example, relating to the tolerance of microcapsule diameter and membrane thickness distributions. Qualitative indices representing fibrosis and device properties (e.g., sphericity) are also used to describe the need for in vitro experiments in the development of bioartificial organs.

Bioartificial Organs↗

New multicomponent capsules for immunoisolation.

A new generation of microcapsules based on the use of oligomers which participate in polyelectrolyte complexation reactions has been developed. These freeze-thaw stable capsules have been applied as a bioartificial pancreas and have resulted in normoglycemia for periods of six months in concordant xenotransplantations. The new chemistry permits the control of permeability and mechanical properties over a wide range and can be adapted both to microcapsule and hollow fiber geometries rendering it a robust tool for encapsulation in general. Methods, and metrics, for the characterization of the mechanical properties and permeability of microcapsules are presented.

Artificial Organs↗

Transesterification of phenylalanine by means of chymotrypsin in a continuous fixed bed reactor.

An enzymic transesterification was carried out in a continuously operated fixed bed reactor. The reaction system consisted of immobilized alpha-chymotrypsin (E.C. 3.4.21.1) catalysing the transfer of the L-phenylalanine radical from the racemic propyl ester to 1,4-butanediol, yielding L-phenylalanine 4-hydroxybutyl ester. The desired reaction was accompanied by alcoholysis due to the presence of 1-propanol liberated during the reaction and by hydrolysis of both the propyl and the hydroxybutyl ester. The problem of shifting pH during the reaction due to ester hydrolysis was overcome by adjusting the initial pH of the substrate feed solution appropriately in order to obtain a sufficiently high buffer capacity provided by the free amino group of the esters. Thus, it was possible to work with shifting pH, an obvious disadvantage for operating reactors of low backmixing for this kind of reaction system. The overall reaction scheme was characterized by the appearance of a maximum ester yield as a function of the operating time in case of batch reactors. Surprisingly, the yield was found to become constant as a function of space-time for continuous operation due to a steeper pH drop. The maximum productivity achieved with respect to the hydroxybutyl ester was about 65 mol d-1 l-1 referred to the catalyst volume.

Butylene Glycols↗

The production of alpha-cyclodextrin by enzymatic degradation of starch.

The maximum concentration of alpha-cyclodextrin for the enzymatic degradation of starch is limited to about 13.5 g X 1(-1). By addition of decanol, the equilibrium of the reaction system can be shifted towards an alpha-cyclodextrin yield of 50% even at high substrate concentrations. The main variables of the decanol process--pH, temperature, substrate quality, substrate, and enzyme concentration--have been studied. The cyclodextrin-glycosyltransferase from Klebsiella pneumoniae M5 al can preferentially be employed at pH 6 to 8, temperatures of 40 to 50 degrees C and a decanol concentration of 0.1 kg-1 starch. The dextrose equivalent of starch is important with respect to the maximum achievable starch concentration, but not with respect to the reaction. Under process conditions, the rate of alpha-cyclodextrin evolution is limited by the enzymatic reaction and not by mass transfer of decanol into the aqueous phase.

Cyclodextrins↗