Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing

Li, Quan; Qi, Guangyan; Lutter, Dylan; Beard, Warren L.; Souza, Camila R.S.; Highland, Margaret A.; Wu, Wei; Li, Ping; Zhang, Yuanyuan; Atala, Anthony; Sun, Xiuzhi Susan

doi:10.3390/biom12091317

Cited by 12 publications

(6 citation statements)

References 81 publications

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“…One study encapsulated human adipose derived mesenchymal stem cells (hADMSCs) in novel peptide‐based PGmatrix hydrogels and tested the effect of encapsulation on cell viability and gene expression. Results indicated that cell encapsulated in PGmatrix secreted more immune‐responsive proteins compared to HA encapsulated cells, and had improved skin wound healing in an in vivo diabetic mouse model 53 . This study shows that the microenvironment of MSCs can affect gene expression, thereby improving wound healing through the upregulation of protein expression in an environment‐dependent manner.…”

Section: Skin/wound Healingmentioning

confidence: 75%

“…Results indicated that cell encapsulated in PGmatrix secreted more immune-responsive proteins compared to HA encapsulated cells, and had improved skin wound healing in an in vivo diabetic mouse model. 53 This study shows that the microenvironment of MSCs can affect gene expression, thereby improving wound healing through the upregulation of protein expression in an environmentdependent manner.…”

Section: Other Methodsmentioning

confidence: 82%

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Cell‐instructive biomaterials in tissue engineering and regenerative medicine

Adhikari

Stager

Krebs

2023

J Biomedical Materials Res

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The field of biomaterials aims to improve regenerative outcomes or scientific understanding for a wide range of tissue types and ailments. Biomaterials can be fabricated from natural or synthetic sources and display a plethora of mechanical, electrical, and geometrical properties dependent on their desired application. To date, most biomaterial systems designed for eventual translation to the clinic rely on soluble signaling moieties, such as growth factors, to elicit a specific cellular response. However, these soluble factors are often limited by high cost, convoluted synthesis, low stability, and difficulty in regulation, making the translation of these biomaterials systems to clinical or commercial applications a long and arduous process. In response to this, significant effort has been dedicated to researching cell‐directive biomaterials which can signal for specific cell behavior in the absence of soluble factors. Cells of all tissue types have been shown to be innately in tune with their microenvironment, which is a biological phenomenon that can be exploited by researchers to design materials that direct cell behavior based on their intrinsic characteristics. This review will focus on recent developments in biomaterials that direct cell behavior using biomaterial properties such as charge, peptide presentation, and micro‐ or nano‐geometry. These next generation biomaterials could offer significant strides in the development of clinically relevant medical devices which improve our understanding of the cellular microenvironment and enhance patient care in a variety of ailments.

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Section: Skin/wound Healingmentioning

confidence: 75%

Section: Other Methodsmentioning

confidence: 82%

Cell‐instructive biomaterials in tissue engineering and regenerative medicine

Adhikari

Stager

Krebs

2023

J Biomedical Materials Res

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“…The biocompatibility of the CS-CHO(H)/HA-SH hydrogel was investigated by seeding Normal Human Dermal Fibroblasts (NHDFs) onto the hydrogel surface and a commercially available HA-based cell culture hydrogel kit (Hystem ® ) at a density of 1.0 × 10 5 /well. Researchers have widely adopted Hystem ® hydrogel as a commercially available substrate that can provide a three-dimensional (3D) scaffold for cell culture, therefore it was selected as the control comparison for the viability study [ 35 , 36 ]. The cell viability was evaluated by the alamarBlue assay and imaged by the LIVE/DEAD assay at 24 h and 72 h. Compared to the commercial hydrogel, CS-CHO(H)/HA-SH emitted approximately 5 times more fluorescence at 72 h ( Figure 5 a), and only a few dead cells (stained in red) were visible in the LIVE/DEAD images ( Figure 5 b).…”

Section: Resultsmentioning

confidence: 99%

Hyaluronic Acid/Chondroitin Sulfate-Based Dynamic Thiol–Aldehyde Addition Hydrogel: An Injectable, Self-Healing, On-Demand Dissolution Wound Dressing

Johnson,

Song,

et al. 2024

Materials

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Frequent removal and reapplication of wound dressings can cause mechanical disruption to the healing process and significant physical discomfort for patients. In response to this challenge, a dynamic covalent hydrogel has been developed to advance wound care strategies. This system comprises aldehyde functionalized chondroitin sulfate (CS-CHO) and thiolated hyaluronic acid (HA-SH), with the distinct ability to form in situ via thiol–aldehyde addition and dissolve on-demand via the thiol–hemithioacetal exchange reaction. Although rarely reported, the dynamic covalent reaction of thiol–aldehyde addition holds great promise for the preparation of dynamic hydrogels due to its rapid reaction kinetics and easy reversible dissociation. The thiol–aldehyde addition chemistry provides the hydrogel system with highly desirable characteristics of rapid gelation (within seconds), self-healing, and on-demand dissolution (within 30 min). The mechanical and dissolution properties of the hydrogel can be easily tuned by utilizing CS-CHO materials of different aldehyde functional group contents. The chemical structure, rheology, self-healing, swelling profile, degradation rate, and cell biocompatibility of the hydrogels are characterized. The hydrogel possesses excellent biocompatibility and proves to be significant in promoting cell proliferation in vitro when compared to a commercial hydrogel (HyStem® Cell Culture Scaffold Kit). This study introduces the simple fabrication of a new dynamic hydrogel system that can serve as an ideal platform for biomedical applications, particularly in wound care treatments as an on-demand dissolvable wound dressing.

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“…Culture conditions modulated hiPSC growth, gene expression, protein secretion, and extracellular vesicle (EV) release. The hiPSCs cultured in the 3D PGmatrix hiPSC system demonstrated the ability to maintain consistently high cell viability above 95% and expansion folds (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) depending on culture conditions, along with stable pluripotent gene expression. The hiPSCs in a 3D culture released significantly higher numbers of unique proteins and EVs than those in a 2D culture.…”

Section: Discussionmentioning

confidence: 99%

Unlocking the Potential of Human-Induced Pluripotent Stem Cells: Cellular Responses and Secretome Profiles in Peptide Hydrogel 3D Culture

Cui,

Wu,

et al. 2024

Cells

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Human-induced pluripotent stem cells (hiPSCs) have shown great potential for human health, but their growth and properties have been significantly limited by the traditional monolayer (2D) cell culture method for more than 15 years. Three-dimensional (3D) culture technology has demonstrated tremendous advantages over 2D. In particular, the 3D PGmatrix hiPSC derived from a peptide hydrogel offers a breakthrough pathway for the maintenance and expansion of physiologically relevant hiPSC 3D colonies (spheroids). In this study, the impact of 3D culture conditions in PGmatrix hiPSC on cell performance, integrity, and secretome profiles was determined across two commonly used hiPSC cell lines derived from fibroblast cells (hiPSC-F) and peripheral blood mononuclear cells (hiPSC-P) in the two most popular hiPSC culture media (mTeSR1 and essential eight (E8)). The 3D culture conditions varied in hydrogel strength, 3D embedded matrix, and 3D suspension matrix. The results showed that hiPSCs cultured in 3D PGmatrix hiPSC demonstrated the ability to maintain a consistently high cell viability that was above 95% across all the 3D conditions with cell expansion rates of 10–20-fold, depending on the 3D conditions and cell lines. The RT-qPCR analysis suggested that pluripotent gene markers are stable and not significantly affected by the cell lines or 3D PGmatrix conditions tested in this study. Mass spectrometry-based analysis of secretome from hiPSCs cultured in 3D PGmatrix hiPSC revealed a significantly higher quantity of unique proteins, including extracellular vesicle (EV)-related proteins and growth factors, compared to those in the 2D culture. Moreover, this is the first evidence to identify that hiPSCs in a medium with a rich supplement (i.e., mTeSR1) released more growth-regulating factors, while in a medium with fewer supplements (i.e., E8) hiPSCs secreted more survival growth factors and extracellular proteins. These findings offer insights into how these differences may impact hiPSC behavior, and they deepen our understanding of how hiPSCs respond to 3D culture conditions, aiding the optimization of hiPSC properties in translational biomedical research toward clinical applications.

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Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing

Cited by 12 publications

References 81 publications

Cell‐instructive biomaterials in tissue engineering and regenerative medicine

Cell‐instructive biomaterials in tissue engineering and regenerative medicine

Hyaluronic Acid/Chondroitin Sulfate-Based Dynamic Thiol–Aldehyde Addition Hydrogel: An Injectable, Self-Healing, On-Demand Dissolution Wound Dressing

Unlocking the Potential of Human-Induced Pluripotent Stem Cells: Cellular Responses and Secretome Profiles in Peptide Hydrogel 3D Culture

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