Plant-derived bioactive compounds are minor constituents of natural plant foods that exist in trace amounts but have validated benefits to human health. Despite the promising evidence on their therapeutic or health-maintaining effects, it cannot be directly translated into dietary recommendations. One of the many challenges is that the fraction of bioactive compounds that can be released from food matrices, defined as bioaccessibility, will be different depending on the compositions and structures of the food matrices and their physical and chemical interactions with the bioactive compound. Majority of the current studies investigated such a food matrix effect on bioaccessibility of plant-derived bioactive compounds by evaluating the effects of different processing techniques and conditions on the bioaccessibility. Considered as a top-down approach, this method often fails to decouple the effects from various contributing mechanisms, such as the chemical and structural factors, since the observed effects are lumped and collective.This research adopted a bottom-up approach to investigate the multi-scale food matrix effect on bioaccessibility of plant-derived bioactive compounds during in vitro digestion. Inspired by natural foods, tissue-like encapsulation systems for bioactive compounds were constructed with different levels of compositional and structural complexities, using yeast-based microcarriers as the building blocks, and techniques such as 3D printing for guided cell assembly. A combined experimental and modeling approach was taken to investigate the bioactive compound – food matrix interactions in the encapsulation systems. The central hypothesis tested in the current research was that the encapsulation and release of bioactive compounds could be affected by the chemical and physical interactions among the bioactive compounds, the encapsulation matrices, and the digestion fluids’ components at different scale levels, i.e., the sub-cellular, cellular, and tissue levels.
The encapsulation of bioactive compounds and their release profiles during in vitro digestion were evaluated for all the cell-based and tissue-like matrices. This research found that at a cellular level, it was mainly the interactions among the bioactive compounds, the cellular components, and the digestion fluids components that controlled the release kinetics. Such interactions included complex formation and dissociation between compounds and cellular proteins, partition among the extracellular environment and intracellular lipid-rich phase and protein-rich aqueous phase, as well as the changes in cellular composition and intracellular structures during digestion. At a tissue level, besides the abovementioned interactions, physical barriers to compounds’ release become more significant, such as diffusion impediment and physical entrapment due to the presence of extracellular matrix or the assembly of single cells. Moreover, this research incorporated the element of in silico evaluation by constructing predictive models for the encapsulation efficiency and release patterns of compounds in cell-based carriers, and printability of food inks. In the effort to construct the in silico evaluation pipelines, we exploited multimodal data to characterize the encapsulation systems and utilized statistical tools and machine learning/ deep learning algorithms for proper feature selection and model training.
Overall, the findings of this research resulted in a better understanding of the bioactive compound – food matrix interaction both during encapsulation and in vitro digestion, demonstrating the possibility to modulate the in vitro release kinetics of bioactive compounds by modifying the chemical or structural features of encapsulation matrices at the cell level or tissue level. Further development of the in silico pipelines for formulation evaluation and optimization could facilitate the design and development of novel nutraceuticals and functional foods
