skip to main content


Title: Engineered Living Hydrogels
Abstract

Living biological systems, ranging from single cells to whole organisms, can sense, process information, and actuate in response to changing environmental conditions. Inspired by living biological systems, engineered living cells and nonliving matrices are brought together, which gives rise to the technology of engineered living materials. By designing the functionalities of living cells and the structures of nonliving matrices, engineered living materials can be created to detect variability in the surrounding environment and to adjust their functions accordingly, thereby enabling applications in health monitoring, disease treatment, and environmental remediation. Hydrogels, a class of soft, wet, and biocompatible materials, have been widely used as matrices for engineered living cells, leading to the nascent field of engineered living hydrogels. Here, the interactions between hydrogel matrices and engineered living cells are described, focusing on how hydrogels influence cell behaviors and how cells affect hydrogel properties. The interactions between engineered living hydrogels and their environments, and how these interactions enable versatile applications, are also discussed. Finally, current challenges facing the field of engineered living hydrogels for their applications in clinical and environmental settings are highlighted.

 
more » « less
Award ID(s):
1935291
NSF-PAR ID:
10445288
Author(s) / Creator(s):
 ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Materials
Volume:
34
Issue:
26
ISSN:
0935-9648
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Hydrogels are commonly used as engineered extracellular matrix (ECM) mimics in applications ranging from tissue engineering to in vitro disease models. Ideal mechanisms used to crosslink ECM‐mimicking hydrogels do not interfere with the biology of the system. However, most common hydrogel crosslinking chemistries exhibit some form of crossreactivity. The field of bioorthogonal chemistry has arisen to address the need for highly specific and robust reactions in biological contexts. Accordingly, bioorthogonal crosslinking strategies are incorporated into hydrogel design, allowing for gentle and efficient encapsulation of cells in various hydrogel materials. Furthermore, the selective nature of bioorthogonal chemistries can permit dynamic modification of hydrogel materials in the presence of live cells and other biomolecules to alter matrix mechanical properties and biochemistry on demand. This review provides an overview of bioorthogonal strategies used to prepare cell‐encapsulating hydrogels and highlights the potential applications of bioorthogonal chemistries in the design of dynamic engineered ECMs.

     
    more » « less
  2. Polyurethanes (PUs) are a highly adaptable class of biomaterials that are among some of the most researched materials for various biomedical applications. However, engineered tissue scaffolds composed of PU have not found their way into clinical application, mainly due to the difficulty of balancing the control of material properties with the desired cellular response. A simple method for the synthesis of tunable bioactive poly(ethylene glycol) diacrylate (PEGDA) hydrogels containing photocurable PU is described. These hydrogels may be modified with PEGylated peptides or proteins to impart variable biological functions, and the mechanical properties of the hydrogels can be tuned based on the ratios of PU and PEGDA. Studies with human cells revealed that PU–PEG blended hydrogels support cell adhesion and viability when cell adhesion peptides are crosslinked within the hydrogel matrix. These hydrogels represent a unique and highly tailorable system for synthesizing PU-based synthetic extracellular matrices for tissue engineering applications.

     
    more » « less
  3. Abstract

    Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native‐like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non‐traditional magnetics‐based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels. Rather than magnetizing the objects within the hydrogel, the magnetic susceptibility of the surrounding hydrogel precursor solution is enhanced. In this way, a range of diamagnetic objects (e.g., polystyrene beads, drug delivery microcapsules, and living cells) are patterned in response to a brief exposure to a magnetic field. Upon photo‐crosslinking the hydrogel precursor, object positioning is maintained, and the magnetic contrast agent diffuses out of the hydrogel, supporting long‐term construct viability. This approach is applied to engineer cartilage constructs with a depth‐dependent cellularity mirroring that of native tissue. These are thought to be the first results showing that magnetically unaltered cells can be magneto‐patterned in hydrogels and cultured to generate heterogeneous tissues. This work provides a foundation for the formation of opposing magnetic‐susceptibility‐based gradients within a single continuous material.

     
    more » « less
  4. Abstract

    The field of engineered living materials lies at the intersection of materials science and synthetic biology with the aim of developing materials that can sense and respond to the environment. In this study, we use 3D printing to fabricate a cyanobacterial biocomposite material capable of producing multiple functional outputs in response to an external chemical stimulus and demonstrate the advantages of utilizing additive manufacturing techniques in controlling the shape of the fabricated photosynthetic material. As an initial proof-of-concept, a synthetic riboswitch is used to regulate the expression of a yellow fluorescent protein reporter inSynechococcus elongatusPCC 7942 within a hydrogel matrix. Subsequently, a strain ofS. elongatusis engineered to produce an oxidative laccase enzyme; when printed within a hydrogel matrix the responsive biomaterial can decolorize a common textile dye pollutant, indigo carmine, potentially serving as a tool in environmental bioremediation. Finally, cells are engineered for inducible cell death to eliminate their presence once their activity is no longer required, which is an important function for biocontainment and minimizing environmental impact. By integrating genetically engineered stimuli-responsive cyanobacteria in volumetric 3D-printed designs, we demonstrate programmable photosynthetic biocomposite materials capable of producing functional outputs including, but not limited to, bioremediation.

     
    more » « less
  5. Abstract

    Living materials are created through the embedding of live, whole cells into a matrix that can house and sustain the viability of the encapsulated cells. Through the immobilization of these cells, their bioactivity can be harnessed for applications such as bioreactors for the production of high‐value chemicals. While the interest in living materials is growing, many existing materials lack robust structure and are difficult to pattern. Furthermore, many living materials employ only one type of microorganism, or microbial consortia with little control over the arrangement of the various cell types. In this work, a Pluronic F127‐based hydrogel system is characterized for the encapsulation of algae, yeast, and bacteria to create living materials. This hydrogel system is also demonstrated to be an excellent material for additive manufacturing in the form of direct write 3D‐printing to spatially arrange the cells within a single printed construct. These living materials allow for the development of incredibly complex, immobilized consortia, and the results detailed herein further enhance the understanding of how cells behave within living material matrices. The utilization of these materials allows for interesting applications of multikingdom microbial cultures in immobilized bioreactor or biosensing technologies.

     
    more » « less