One‐Step All‐Aqueous Interfacial Assembly of Robust Membranes for Long‐Term Encapsulation and Culture of Adherent Stem/Stromal Cells

Abstract

The therapeutic effectiveness and biological relevance of technologies based on adherent cells depend on platforms that enable long-term culture in controlled environments. Liquid-core capsules have been suggested as semipermeable moieties with spatial homogeneity due to the high mobility of all components in their core. The lack of cell-adhesive sites in liquid-core structures often hampers their use as platforms for stem cell-based technologies for long-term survival and cell-directed self-organization. Here, the one-step fast formation of robust polymeric capsules formed by interfacial complexation of oppositely charged polyelectrolytes in an all-aqueous environment, compatible with the simultaneous encapsulation of mesenchymal stem/stromal cells (MSCs) and microcarriers, is described. The adhesion of umbilical cord MSCs to polymeric microcarriers enables their aggregation and culture for more than 21 days in capsules prepared either manually by dropwise addition, or by scalable electrohydrodynamic atomization, generating robust and stable capsules. Cell aggregation and secretion overtime can be tailored by providing cells with static or dynamic (bioreactor) environments.

Design of Protein‐Based Liquefied Cell‐Laden Capsules with Bioinspired Adhesion for Tissue Engineering

“…As already stated, some liquefied platforms are enriched with the inclusion of microparticles as cell adhesion substrates. [9,10] In our specific case, the micro-sized hydrogel shell by itself seems to provide both ECM-mimic adhesion motifs and suitable mechanical cues for cell growth and proliferation, without evident formation of cellular aggregates.…”

“…[3] Up to date, a wide variety of polymers DOI: 10.1002/adhm.202100782 (synthetic and natural), biofabrication technologies (e.g., electrospray, microfluidic, among others) and approaches (e.g., layer-by-layer, aqueous biphasic systems) are underneath the design of a shell confinement (i.e., a barrier able to confine cells in a controlled environment). [4][5][6][7][8][9] However, most of those systems resort to the combination of synthetic and natural polymers to create cell confinement, limiting its translation into the clinic. Although these approaches can engineer self-organized microtissues with the cells enclosed in a semipermeable shell, as most mammalian cells require a solid matrix for attachment, the inclusion of synthetic microcarriers (e.g., microparticles) is sometimes required.…”

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“…Polymers usually are classified into two types according to their solubility: oil-soluble polymers and water-soluble polymers. This technique has been described in the literature [ 37 , 38 , 53 ]. Briefly, the polymer is made into an emulsion of O/W (oil-in water), W/O (water-in-oil), W1/O/W2 (water-in-oil-in-water) or O/W/O (oil-in-water-in-oil) using different emulsification processes ( Fig.…”

“…Microcarriers are generally described as microparticles made from natural or synthetic materials with sizes ranging from 1 μm to 1000 μm, that are widely used in drug/cell delivery, regenerative medicine, and TE [ 33 , 34 ]. Moreover, microcarriers have been applied as microspherical scaffolds in biological and biomedical applications such as cell culture, expansion, delivery, modeling for biological studies, biosensor, and medical implants [ [35] , [36] , [37] , [38] ]. To date, a variety of biomaterials have been developed to fabricate microcarriers using various techniques and methods, such as bioactive inorganic materials, natural/synthetic polymers, and their composites [ [39] , [40] , [41] ].…”

Biohybrid materials: Structure design and biomedical applications

“…In addition to single-cell encapsulation, there are cases where a population of cells are encapsulated, and the resultant biohybrid microparticles could be used for cell culturing, delivery, etc [ [42] , [43] , [44] , [45] , [46] , [47] , [48] ]. Biohybrid microparticles could be generated from microfluidic droplets, where maintaining a high viability of cells is a prerequisite [ 46 ].…”