Multiscale requirements for bioencapsulation in medicine and biotechnology

Abstract

Bioencapsulation involves the envelopment of tissues or biological active substances in semipermeable membranes. Bioencapsulation has been shown to be efficacious in mimicking the cell's natural environment and thereby improves the efficiency of production of different metabolites and therapeutic agents. The field of application is broad. It is being applied in bioindustry and biomedicine. It is clinically applied for the treatment of a wide variety of endocrine diseases. During the past decades many procedures to fabricate capsules have been described. Unfortunately, most of these procedures lack an adequate documentation of the characterization of the biocapsules. As a result many procedures show an extreme lab-to-lab variation and many results cannot be adequately reproduced. The characterization of capsules can no longer be neglected, especially since new clinical trials with bioencapsulated therapeutic cells have been initiated and the industrial application of bioencapsulation is growing. In the present review we discuss novel Approached to produce and characterize biocapsules in view of clinical and industrial application. A dominant factor in bioencapsulation is selection and characterization of suitable polymers. We present the adequacy of using high-resolution NMR for characterizing polymers. These polymers are applied for producing semipermeable membranes. We present the pitfalls of the currently applied methods and provide recommendations for standardization to avoid lab-to-lab variations. Also, we compare and present methodologies to produce biocompatible biocapsules for specific fields of applications and we demonstrate how physico-chemical technologies such as FT-IR, XPS, and TOF-SIMS contribute to reproducibility and standardization of the bioencapsulation process. During recent years it has become more and more clear that bioencapsulation requires a multidisciplinary approach in which biomedical, physical, and chemical technologies are combined. For adequate reproducibility and for understanding variations in outcome of biocapsules it is advisable if not mandatory to include the characterization processes presented in this review in future studies.

Introduction

Bioencapsulation involves the envelopment of tissues or biological active substances in a semipermeable membrane to protect the enclosed biological structures for potential hazardous processes in the direct environment. The field of application of bioencapsulation is broad. In plant cell cultures [1], [2], [3], bioencapsulation has been shown to be efficacious in mimicking the cell's natural environment. Thereby bioencapsulation improves the efficiency of production of different metabolites for industrial application. For fermentation [4], [5], [6], [7], [8] bioencapsulation is being applied for enlarging the cell density, aroma and capacity of the systems. Additionally during fermentation it avoids washout of the biological catalysts from the reactor. Bioencapsulation also has a pertinent application in medicine. It is, for example, applied to protect biological active substances or cells such as probiotica to the deleterious biological environment [9], [10], [11], [12] and for delivery in specific sites such as the colon [13], [14]. A relatively large group of researchers apply bioencapsulation for the creation of a bioartificial organ [15]. In this application, therapeutic cells are encapsulated in membranes that protect the cells against antibodies and cytotoxic cells of the host immune system. This immunoisolation by encapsulation has a number of important benefits for clinical application of transplantation. First of all, it avoids the use of systemic and permanent immunosuppression. Immunosuppression has serious side effects such as a higher chance for malignancies and frequent infections. Another benefit is that encapsulation allows for successful transplantation of cells from nonhuman origin, i.e. xenografts, which could be a mean of overcoming the obstacle of limited supply of donor tissue [16]. The principal applicability of the technology has been shown for the treatment of a wide variety of endocrine diseases, including anemia [17], dwarfism [18], hemophilia B [19], kidney [20] and liver [21] failure, pituitary [22] and central nervous system insufficiencies [23], and diabetes mellitus [24].

During the past decades many procedures to fabricate capsules have been described. Unfortunately, most of these procedures are dedicated to the technology of the production process but lack an adequate documentation of the characterization of the capsule. As a result many procedures show an extreme lab-to-lab variation and many results cannot be adequately reproduced. The characterization of capsules can no longer be neglected, especially since new clinical trials with bioencapsulated therapeutic cells have been initiated [25] and the industrial application of bioencapsulation is growing. During recent years many technologies have been described to characterize capsule properties. In the present review we discuss these technologies in view of clinical and industrial applications.