Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants

Edri, Reuven; Gal, Idan; Noor, Nadav; Harel, Tom; Fleischer, Sharon; Adadi, Nofar; Green, Ori; Shabat, Doron; Heller, Lior; Shapira, Assaf; Gat‐Viks, Irit; Peer, Dan; Dvir, Tal

doi:10.1002/adma.201803895

Cited by 106 publications

(114 citation statements)

References 50 publications

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“…The cells were then efficiently differentiated to cardiomyocytes, exhibiting actinin, connexin‐43, troponin T, and Nkx2.5 markers (Figure 6c,d). Following re‐encapsulation, the cells were spread throughout the droplet, expressing troponin T (Figure 6e). Furthermore, contractions with regularly spaced spikes and beating frequency of ≈1–2 Hz could be clearly seen within the droplets (Figure 6f and Movie S8, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…Obviously, further in vivo experiments should be conducted in order to evaluate the capacity of the system to regenerate specific defected organs. Finally, the use of a personalized hydrogel with the patient's own cells was previously shown to provoke significantly lower immune response, compared to hydrogels originated from animals' ECM . The use of fully personalized cellular droplets where both the cells and the biomaterials are used for encapsulation may have an immunological advantage over the use of other materials.…”

Section: Discussionmentioning

confidence: 99%

“…Omenta were decellularized as previously described . Omenta from healthy pigs (Kibutz Lahav, Israel) were washed with phosphate buffered saline (PBS) (At least five pig omenta were used).…”

Section: Methodsmentioning

confidence: 99%

“…Biological motifs in natural hydrogels also affect cell behavior, including growth, migration, maturation, and differentiation. Recently, our group has developed a personalized hydrogel, based on the omentum extracellular‐matrix (ECM) . The omentum is a highly vascularized fatty tissue with a well‐documented regenerative capabilities, which extends from the stomach overlying the abdomen .…”

Section: Introductionmentioning

confidence: 99%

“…After processing the ECM to generate a personalized hydrogel the stromal cells of the omentum are reprogrammed to pluripotent stem cells and cultured within. We have shown that any tissue implant can be generated in this approach . Here, as a proof of concept, pigs' omental tissues were extracted and the ECM was decellularized and processed to generate a 1% w/v thermoresponsive hydrogel.…”

Section: Introductionmentioning

confidence: 99%

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Injectable Cardiac Cell Microdroplets for Tissue Regeneration

Gal

Edri

Noor

et al. 2020

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One of the strategies for heart regeneration includes cell delivery to the defected heart. However, most of the injected cells do not form quick cell–cell or cell–matrix interactions, therefore, their ability to engraft at the desired site and improve heart function is poor. Here, the use of a microfluidic system is reported for generating personalized hydrogel‐based cellular microdroplets for cardiac cell delivery. To evaluate the system's limitations, a mathematical model of oxygen diffusion and consumption within the droplet is developed. Following, the microfluidic system's parameters are optimized and cardiac cells from neonatal rats or induced pluripotent stem cells are encapsulated. The morphology and cardiac specific markers are assessed and cell function within the droplets is analyzed. Finally, the cellular droplets are injected to mouse gastrocnemius muscle to validate cell retention, survival, and maturation within the host tissue. These results demonstrate the potential of this approach to generate personalized cellular microtissues, which can be injected to distinct regions in the body for treating damaged tissues.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Omenta were decellularized as previously described . Omenta from healthy pigs (Kibutz Lahav, Israel) were washed with phosphate buffered saline (PBS) (At least five pig omenta were used).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Injectable Cardiac Cell Microdroplets for Tissue Regeneration

Gal

Edri

Noor

et al. 2020

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Covalent Cell‐Loading Injectable Hydrogel Scaffold Significantly Promotes Tissue Regeneration In Vivo Compared with a Conventional Physical Cell‐Loading Hydrogel Scaffold

et al. 2021

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Currently, one of the major tendencies to be adopted for the design of hydrogel scaffolds in tissue engineering include that cells are loaded physically into the pores of 3D hydrogel networks. In this study, a drastic deviation from this tendency is proposed and developed a new type of hydrogel scaffold in which cells are covalently connected to 3D hydrogel networks via bioorthogonal click cross‐linking reactions of azide‐modified cells with alkyne‐modified polymers. The purpose of this study is to directly compare the utility of the covalent cell‐loading approach and the conventional physical cell‐loading approach as hydrogel scaffolds for in vivo tissue engineering. It is found that the proposed covalent cell‐loading approach significantly promotes tissue regeneration and functional recovery in vivo in comparison with the conventional physical cell‐loading approach. This is the first report demonstrating the importance of the covalent cell‐loading approach in tissue engineering. This covalent cell‐loading approach is applicable to a broad spectrum of mammalian cells, including stem cells. The present findings provide a promising new route to generate innovative hydrogel scaffolds for in vivo tissue engineering.

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Construction of Nanozyme‐Hydrogel for Enhanced Capture and Elimination of Bacteria

Sang

Líu

et al. 2019

Adv Funct Materials

247

190

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The widespread multidrug resistance resulting from the abuse of antibiotics motivates researchers to explore alternative methods to treat bacterial infections. Recently, the emergence of nanozymes has provided a potential approach to combat bacteria. Such nanozymes can mimic the functions of natural enzymes to induce the production of highly toxic reactive oxygen species (ROS) as an antibacterial. However, the lack of effective interaction between nanozymes and bacteria, and the intrinsic short lifetime and diffusion distance of ROS greatly compromise their bactericidal activity. Furthermore, the dead bacteria left in the infected area can give rise to unexpected tissue inflammation. Herein, for the first time, a nanozyme-hydrogel is constructed to realize reinforced antibacterials. The nanozyme-hydrogel with the traits of positive charge and macropore can capture and restrict bacteria in the range of ROS destruction. Significantly, by combining the near-infrared photothermal property of nanozymes, the nanozyme-hydrogel can achieve a synergistic bactericidal effect. More importantly, the nanozyme-hydrogel can eliminate bacteria and reduce the risk of inflammation. In consequence, the current work manifests an original strategy to improve the antibacterial performance of nanozymes, concurrently promote wound healing.

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Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants

Cited by 106 publications

References 50 publications

Injectable Cardiac Cell Microdroplets for Tissue Regeneration

Injectable Cardiac Cell Microdroplets for Tissue Regeneration

Covalent Cell‐Loading Injectable Hydrogel Scaffold Significantly Promotes Tissue Regeneration In Vivo Compared with a Conventional Physical Cell‐Loading Hydrogel Scaffold

Construction of Nanozyme‐Hydrogel for Enhanced Capture and Elimination of Bacteria

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