Polymeric Microarchitectures for Tissue Regeneration and Drug Screening

Tissue engineering aims to restore malfunctioned tissues by fabricating three-dimensional (3D) biomimetic tissue substitutes that emulate their native counterparts. This field has garnered enormous interest from researchers due to increased organ replacement therapies and the shortage of donors. Several advancements have resulted in the generation of highly organized 3D scaffolds to improve the control over the microenvironment for tissue growth, such as biocompatible fibrous scaffolds, photo-cross-linkable hydrogels, and 3D biodegradable porous scaffolds. Numerous efforts in fabricating artificial tissue constructs have been dedicated to repairing tissue damage and highlighting the significance of vascularization and innervation on tissue maturation. Over the past few decades, diverse preclinical screening methods have been explored to demonstrate the pharmacological and toxicological characteristics of various therapeutic drugs. The traditional cell monolayer-based 2D approach often suffers from limitations in recapitulating the highly complex, natural extracellular matrix (ECM)-like microenvironment. Although the 3D scaffold-free cell aggregates emerged as an alternative to 2D monolayers, they fail to recapitulate key attributes of the natural tumor microenvironment and poor survival rates of cells.

The implantation of bulk scaffolds for tissue repair often utilizes complex surgical procedures, which may generate severe inflammatory reactions resulting in the harsh microenvironment, where the survival of cells remains low. In this context, several biodegradable polymeric microspheres with highly open and interconnected pores have been reported as these carriers enable exceptional cell encapsulation efficacy in their entire volume and facilitate their minimally invasive delivery. Notably, these cell-laden microspheres could further aggregate and form microtissues for tissue engineering applications. Utilizing the 3D polymeric microarchitectures harbored with cells offer enormous advantages in terms of effective cell-harboring and carrying capacities, enabling the supply of oxygen and nutrients for cell proliferation. These injectable modularized units of cell-loaded microspheres, cell lamellae, cell-laden microgels, obtained using various biofabrication strategies, offer ease of packing, minimally invasive, and improved cell retention capacity than direct injection of cells alone. Compared to traditional 2D monolayer and 3D cellular spheroids for drug screening, these cellularized polymeric microarchitectures reflect a more accurate tumor microenvironment in cellular interactions and ECM remolding toward drug evaluation and cancer research. In recent times, these innovative polymeric architectures have been explicitly applied to investigate the pharmacological and toxicological characteristics of drugs.

For this thematic issue, we are in quest of submissions related to advancements in various innovative synthetic strategies and plausible mechanistic elucidations towards the development of polymeric microarchitectures for tissue engineering and drug screening applications. Moreover, we invite researchers to submit the articles exploring the opportunities and challenges relevant to scale-up and the clinical translation of these innovative scaffolding systems with considerations of biosafety and degradability. We also welcome studies on mechanistic understanding of interactions within the biological interfaces to accelerate the efficacy of polymeric microsystems through precise cell delivery and screening of therapeutics at different levels.