Perspective on Constructing Cellulose-Hydrogel-Based Gut-Like Bioreactors for Growth and Delivery of Multiple-Strain Probiotic Bacteria

Abstract

The current perspective presents an outlook on developing gut-like bioreactors with immobilized probiotic bacteria using cellulose hydrogels. The innovative concept of using hydrogels to simulate the human gut environment by generating and maintaining pH and oxygen gradients in the gut-like bioreactors is discussed. Fundamentally, this approach presents novel methods of production as well as delivery of multiple strains of probiotics using bioreactors. The relevant existing synthesis methods of cellulose hydrogels are discussed for producing porous hydrogels. Harvesting methods of multiple strains are discussed in the context of encapsulation of probiotic bacteria immobilized on cellulose hydrogels. Furthermore, we also discuss recent advances in using cellulose hydrogels for encapsulation of probiotic bacteria. This perspective also highlights the mechanism of probiotic protection by cellulose hydrogels. Such novel gut-like hydrogel bioreactors will have the potential to simulate the human gut ecosystem in the laboratory and stimulate new research on gut microbiota.

Algicidal Bacteria: A Review of Current Knowledge and Applications to Control Harmful Algal Blooms

“…Taking advantage of this characteristic, bacteria have been immobilized by embedding or encapsulating into porous matrices to prevent dispersal (reviewed by Mehrotra et al, 2021 ). Bacterial immobilization technology has been utilized in a wide range of disciplines to enhance bacterial activity in a number of applications, including wastewater treatment (e.g., Hou et al, 2020 , 2021 ), degradation of marine oil pollution (e.g., Li et al, 2021c ), and probiotic delivery (e.g., Dimitrellou et al, 2019 ; reviewed by Mettu et al, 2021 ). Algicidal bacteria have also been immobilized to various matrices for HAB mitigation ( Table 3 ), including immobilization in (polyvinyl alcohol-) sodium alginate (e.g., Su et al, 2017 ; Zhang et al, 2018 ; Wang and Coyne, 2020 ; Ouyang et al, 2021 ), cellulose sponge (e.g., Noh et al, 2017 ; Wang and Coyne, 2020 ), polyester (e.g., Wang and Coyne, 2020 ), polyurethane (e.g., Kang et al, 2007 ), agarose (e.g., Wang and Coyne, 2020 ), agar (e.g., Kang et al, 2007 ), and coconut fibers (e.g., He et al, 2021 ).…”

Novel Developments on Stimuli-Responsive Probiotic Encapsulates: From Smart Hydrogels to Nanostructured Platforms

“…Another approach suggests that combining polymeric platforms with nanocrystals derived from polysaccharides (e.g., cellulose and starch) enhances mechanical stability and shelling properties [154], and increases the surface area for target delivery [155]. For instance, when cellulose nanocrystals (NCs) are combined with alginate during the microencapsulation process, the dissolution time increases while porosity is reduced significantly [156].…”

“…From a design point of view, the enzyme-responsive material must contain substrate mimics recognition motifs for effective active site binding or substrates capable of interacting with the enzyme molecules without imparting detrimental conformational changes (i.e., significant secondary and tertiary structural changes) [181]. Although to our knowledge, this approach has not been implemented for probiotic encapsulation and delivery purposes, it might be suitable for this task, given the possibility of incorporating wellknown ester molecules (e.g., triglycerol monostearate and ascorbyl palmitate) into the polymeric matrices, which are recognizable by several promiscuous enzymes [154,182]. Additionally, exogenous enzymes can be potentially crosslinked with polymeric matrices such that their release upon degradation at the site of action accelerates probiotics and other cargo delivery even further.…”

Hydrogels as promising platforms for engineered living bacteria-mediated therapeutic systems

“…Local administration is another important option that can effectively improve the concentration of engineered therapeutic bacteria at the target site and reduce the microbial clearance rate as well as the potential risk of systemic infection [ 7 , 11 ]. Notably, the use of living bacteria hydrogel formulations has emerged as a promising method for the local delivery of engineered therapeutic bacterial strains and bacteriotherapy [ [12] , [13] , [14] ].…”