Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Shou, Yufeng; Liu, Ling; Liu, Qimin; Le, Zhicheng; Lee, Khang Leng; Li, Hua; Li, Xianlei; Koh, Dion Zhanyun; Wang, Yuwen; Liu, Tongming; Yang, Zheng; Lim, Chwee Teck; Cheung, Christine; Tay, Andy

doi:10.1016/j.bioactmat.2022.12.019

Cited by 14 publications

(20 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such application is to better balance different cell functions (e.g., proliferation and stemness of mesenchymal stem cells) to achieve optimal quality and quantity. [153] Currently, with development in technologies such as 3D printing fabrication, functionalized biomaterials, microfluidic platform, and external actuation devices, dynamic mechanical stimulation is becoming more accessible for research and clinical translation. With a deeper understanding of how dynamic forces affect cell activities, the positive effects accompanying such mechanical stimulation can be exploited in biomedical applications.…”

Section: Discussionmentioning

confidence: 99%

“…One such application is to better balance different cell functions (e.g., proliferation and stemness of mesenchymal stem cells) to achieve optimal quality and quantity. [ 153 ]…”

Section: Discussionmentioning

confidence: 99%

“…Regulated chondrocyte markers, hypertrophy [199] Stretching ±1%/2 days, 4-16%, 50% ON/OFF (3, 6, or 9 h) Optimal regime for MSC matrix production [190] Vibration 0.3, 3, or 6 g loads, 100 Hz Enhanced osteogenesis (low/medium), inhibited (high) [173] Force loading 1.6 pN per microparticle, 0.1 Hz Increased MSC behaviors, osteogenesis, reduced chondrogenesis [153] of cell products designed for applications such as cartilage and bone regeneration which are ≈18% of existing clinical trials using mesenchymal stem cells. [354]…”

Section: Mechano-stimulated Hydrogel To Enhance Clinical Translationmentioning

confidence: 99%

“…More importantly, when used as surface attachments (e.g., wound site) or in vivo implants, these hydrogels can function as programmable cell‐loaded matrix or mechano‐bioreactor through external stimulation. [ 153 ] Notably, due to cell specificity, a single mechanical stimulus can result in markedly different behaviors in different cell types. This section will focus on hydrogel engineering to mechanically modulate cell types such as mesenchymal stem cells (MSCs), fibroblasts, epithelial cells and immune cells, which have been approved by the U.S. Food and Drug Administration (FDA) for therapeutic use.…”

Section: Engineering Hydrogel For Cellular Mechanical Stimulationmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Shou

Teo

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

show abstract

Section: Discussionmentioning

confidence: 99%

“…One such application is to better balance different cell functions (e.g., proliferation and stemness of mesenchymal stem cells) to achieve optimal quality and quantity. [ 153 ]…”

Section: Discussionmentioning

confidence: 99%

Section: Mechano-stimulated Hydrogel To Enhance Clinical Translationmentioning

confidence: 99%

Section: Engineering Hydrogel For Cellular Mechanical Stimulationmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Shou

Teo

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…In recent years, methods for dynamic magnetic actuation have been described for cellular actuation due to its capacity for inducing precisely controlled mechanical stimulation without physical contact with cells and tissues. [19][20][21] With the integration of magneto-responsive hydrogels, several dynamic platforms have been developed for in vitro applications, such as stem cell manufacturing, [22] neuromodulation, [23] and tumor growth monitoring. [24] In the realm of in vivo therapy, various studies have explored promising areas such as bone regeneration [25] and antitumor therapy.…”

Section: Introductionmentioning

confidence: 99%

Mechano‐Activated Cell Therapy for Accelerated Diabetic Wound Healing

Shou,

Le,

Cheng

et al. 2023

Advanced Materials

Self Cite

View full text Add to dashboard Cite

Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. We developed a powerful platform technology combining magneto‐responsive hydrogel, cells, and wireless magneto‐induced dynamic mechanical stimulation (MDMS) to accelerate diabetic wound healing. Our hydrogel encapsulates FDA‐approved fibroblasts and keratinocytes to achieve ∼3‐fold better wound closure in a diabetic mouse model. MDMS acts as a non‐genetic mechano‐rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto‐responsive property also enables on‐demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, we identified a mechanosensitive fibroblast subpopulation that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. Our “all‐in‐one” system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.This article is protected by copyright. All rights reserved

show abstract

Attenuating Epithelial‐to‐Mesenchymal Transition in Cancer through Angiopoietin‐Like 4 Inhibition in a 3D Tumor Microenvironment Model

Liao,

Lim,

Lee

et al. 2023

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

Epithelial‐to‐mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short in recapitulating the complexity of a 3D tumor microenvironment. To address this limitation, a transcriptomic meta‐analysis is conducted on diverse cancer types undergoing EMT in 2D and 3D cultures. It is found that mechanotransduction is elevated in 3D cultures and is further intensified during EMT, but not during 2D EMT. This analysis reveals a distinct 3D EMT gene signature, characterized by extracellular matrix remodeling coordinated by angiopoietin‐like 4 (Angptl4) along with other canonical EMT regulators. Utilizing hydrogel‐based 3D matrices with adjustable mechanical forces, 3D cancer cultures are established at varying physiological stiffness levels. A YAP:EGR‐1 mediated up‐regulation of Angptl4 expression is observed, accompanied by an upregulation of mesenchymal markers, at higher stiffness during cancer EMT. Suppression of Angptl4 using antisense oligonucleotides or anti‐cAngptl4 antibodies leads to a dose‐dependent abolishment of EMT‐mediated chemoresistance and tumor self‐organization in 3D, ultimately resulting in diminished metastatic potential and stunted growth of tumor xenografts. This unique programmable 3D cancer cultures simulate stiffness levels in the tumor microenvironment and unveil Angptl4 as a promising therapeutic target to inhibit EMT and impede cancer progression.

show abstract

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Cited by 14 publications

References 98 publications

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Mechano‐Activated Cell Therapy for Accelerated Diabetic Wound Healing

Attenuating Epithelial‐to‐Mesenchymal Transition in Cancer through Angiopoietin‐Like 4 Inhibition in a 3D Tumor Microenvironment Model

Contact Info

Product

Resources

About