Cell macroencapsulation devices in contemporary research: A systematic review

Abstract

Cell macroencapsulation devices (CMDs) represent a promising therapeutic approach by combining controlled, off-the-shelf technology with living tissue functionality. Despite their potential, the current knowledge about CMD development and implementation remains fragmented across different applications. We conducted a systematic review to synthesize the available evidence on implantable CMDs and establish a comprehensive framework for their development. Our analysis cataloged studies based on device materials and design, cell types, implantation strategies, and evaluation methods. The review revealed that CMD development has largely progressed in application-specific silos, with varying approaches to device characterization, cell selection (from xenogeneic to autologous), and assessment methods. Key evaluation parameters included cell survival and functionality, host tissue response (inflammation, vascularization, and fibrosis), and therapeutic efficacy. While successful implementations exist across multiple applications, the lack of standardized development and evaluation protocols emerges as a significant barrier to cross-application advancement. These findings highlight the need for unified assessment frameworks to accelerate CMD development across therapeutic applications.

Keywords: Bioencapsulation; Biomedical devices; Cell encapsulation; Implantation; Therapeutic delivery.

Fig. 1

Search parameters and inclusion criteria for studies in this review.

Fig. 2

Distribution of studies in the categories: therapeutic goals, cell source, animal model, and implantation site.

Fig. 3

Device shapes in CMD research. Illustration of the two primary device shapes found in the studies: flat and cylindrical.

Fig. 4

Device characteristics and readout parameters. Left: device features such as materials, cells, and coatings. Right: most common readout assays identified in this review: A: Tissue response accommodation, showing fibrotic and vascularizing tissue responses. B: Sustained cellular integrity within the device, focusing on cell viability and differentiation. C: Detection of secreted products in the host’s circulation and their effects on animal mortality and morbidity.

Fig. 5

Implantation sites in animal models used in CMD research. Illustration of the primary implantation sites used in CMD: nervous system, subcutaneous, and intra-abdominal regions. A rat is used as example animal, but these sites were identified in all animal models.

Fig. 6

Decade-wise trends in CMD study characteristics (a–h). Each chart displays the percentage of studies per decade, covering: (a) device shape (cylindrical vs. flat), (b) device type (self-made, CytoTherapeutics, or TheraCyte), (c) membrane material (PAAV, PTFE, AN-69, PES), (d) implantation site (abdominal cavity, nervous system, subcutaneous, or other), (e) cell source (allogeneic, xenogeneic, or multiple), (f) use of transfected cells, (g) animal models (mice, rats, or other), and (h) adherence to ethical guidelines.