Microgels

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.

Microfluidics has recently emerged as a powerful tool in generation of submillimeter-sized cell aggregates capable of performing tissue-specific functions, so-called microtissues, for applications in drug testing, regenerative medicine, and cell therapies. In this work, we review the most recent advances in the field, with particular focus on the formulation of cell-encapsulating microgels of small "dimensionalities": "0D" (particles), "1D" (fibers), "2D" (sheets), etc., and with nontrivial internal topologies, typically consisting of multiple compartments loaded with different types of cells and/or biopolymers. Such structures, which we refer to as topological hydrogels or topological microgels (examples including core-shell or Janus microbeads and microfibers, hollow or porous microstructures, or granular hydrogels) can be precisely tailored with high reproducibility and throughput by using microfluidics and used to provide controlled "initial conditions" for cell proliferation and maturation into functional tissue-like microstructures. Microfluidic methods of formulation of topological biomaterials have enabled significant progress in engineering of miniature tissues and organs, such as pancreas, liver, muscle, bone, heart, neural tissue, or vasculature, as well as in fabrication of tailored microenvironments for stem-cell expansion and differentiation, or in cancer modeling, including generation of vascularized tumors for personalized drug testing. We review the available microfluidic fabrication methods by exploiting various cross-linking mechanisms and various routes toward compartmentalization and critically discuss the available tissue-specific applications. Finally, we list the remaining challenges such as simplification of the microfluidic workflow for its widespread use in biomedical research, bench-to-bedside transition including production upscaling, further in vivo validation, generation of more precise organ-like models, as well as incorporation of induced pluripotent stem cells as a step toward clinical applications.

In-situ bioprinting is attractive for directly depositing the therapy bioink at the defective organs to repair them, especially for occupations such as soldiers, athletes, and drivers who can be injured in emergency. However, traditional bioink displays obvious limitations in its complex operation environments. Here, we design a bioconcrete bioink with electrosprayed cell-laden microgels as the aggregate and gelatin methacryloyl (GelMA) precursor solution as the cement. Promising printability is guaranteed with a wide temperature range benefiting from robust rheological properties of photocrosslinked microgel aggregate and fluidity of GelMA cement. Composite components simultaneously self-adapt to biocompatibility and different tissue mechanical microenvironment. Strong binding on tissue-hydrogel interface is achieved by hydrogen bonds and friction when the cement is photocrosslinked. This bioink owns good portability and can be easily prepared in urgent accidents. Meanwhile, microgels can be cultured to mini tissues and then mixed as bioink aggregates, indicating our bioconcrete can be functionalized faster than normal bioinks. The cranial defects repair results verify the superiority of this bioink and its potential in clinical settings required in in-situ treatment.

Bone remodeling is a tightly regulated process essential for skeletal health, occurring within specialized structures known as bone multicellular units (BMUs). Despite extensive research, current animal models and conventional in vitro systems fail to reproduce the spatial and cellular complexity of human BMUs. Moreover, the mineralized nature of bone tissue poses imaging challenges due to its inherent opacity, limiting the ability to monitor osteoclast activity in complex 3D models. Control over the structure of in vitro BMU micro-confined niches would enable more effective 3D analysis readouts of osteoclast activity. Herein we developed a BMU-inspired bone-on-chip platform that enables localized, non-invasive analysis of human osteoclast function. Using microfluidic droplet generation, we encapsulated mature osteoclasts in monodisperse, enzymatically degradable dextran-tyramine (Dex-TA) microgels with defined size. These osteoclast-laden microgels were embedded within mineralized collagen hydrogels and selectively degraded to form confined, cell-populated microstructures directly on-chip. In addition, the contrast between the microcavities and surrounding mineralized matrix allowed non-destructive monitoring of matrix degradation using reflection confocal microscopy. Immunocytochemical analysis confirmed the morphological and functional differentiation of osteoclasts within the platform. Furthermore, our results demonstrated increased matrix resorption in response to RANKL treatment, validating the system's capacity to assess osteoclast activity under relevant stimuli. This bone-on-chip model overcomes key limitations of traditional systems by enabling spatial confinement, controlled degradation, and functional readouts of osteoclast behavior in a human-relevant 3D microenvironment. It is thus a versatile tool for studying bone remodeling and has strong potential for application in disease modeling and drug screening for bone-related disorders.