Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing

Dong, Yixiao; Sigen, A; Rodrigues, Melanie; Li, Xin; Kwon, Sun Hyung; Kosaric, Nina; Khong, Sacha; Gao, Yongsheng; Wang, Wenxian; Gurtner, Geoffrey C.

doi:10.1002/adfm.201606619

Cited by 262 publications

(159 citation statements)

References 66 publications

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“…[ 4b,23 ] The shear force can often damages the cells. [ 24 ] Previous studies revealed that hydrogels with shear thinning properties can protect the cells from the damage during injection, improving the viability of MSCs at wound sites. [ 6,25 ] To evaluate the protective effect of the SFN hydrogels, the cell‐free SFN‐LP hydrogels were injected (14 G needles) and the size of the LPs were measured after injection.…”

Section: Resultsmentioning

confidence: 99%

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Zheng

Ding

Cheng

et al. 2020

Adv Healthcare Materials

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Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

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Section: Resultsmentioning

confidence: 99%

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Zheng

Ding

Cheng

et al. 2020

Adv Healthcare Materials

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“…[11][12][13][14] However, the state-of-the-art technology suffers from particular properties of conductive polymers, such as high hydrophobicity and insolubility, resulting in low adherence to wet substrates and poor penetration into living tissues. [18][19][20] To incorporate new functions to a conductive polymer for biomedical utilities, there are several limits of "add-on" approach because it does not alter the intrinsic properties of the electroconductive hydrogel network. [17] Moreover, a soft conductive adhesive, which can be utilized as injectable material, as well as bio-ink for in situ bioprinting, will close the gap between electroconductive materials and biomaterials, lead to numerous medical and clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Cytocompatible, Injectable, and Electroconductive Soft Adhesives with Hybrid Covalent/Noncovalent Dynamic Network

Patsis

Hauser

et al. 2019

Advanced Science

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Synthetic conductive biopolymers have gained increasing interest in tissue engineering, as they can provide a chemically defined electroconductive and biomimetic microenvironment for cells. In addition to low cytotoxicity and high biocompatibility, injectability and adhesiveness are important for many biomedical applications but have proven to be very challenging. Recent results show that fascinating material properties can be realized with a bioinspired hybrid network, especially through the synergy between irreversible covalent crosslinking and reversible noncovalent self‐assembly. Herein, a polysaccharide‐based conductive hydrogel crosslinked through noncovalent and reversible covalent reactions is reported. The hybrid material exhibits rheological properties associated with dynamic networks such as self‐healing and stress relaxation. Moreover, through fine‐tuning the network dynamics by varying covalent/noncovalent crosslinking content and incorporating electroconductive polymers, the resulting materials exhibit electroconductivity and reliable adhesive strength, at a similar range to that of clinically used fibrin glue. The conductive soft adhesives exhibit high cytocompatibility in 2D/3D cell cultures and can promote myogenic differentiation of myoblast cells. The heparin‐containing electroconductive adhesive shows high biocompatibility in immunocompetent mice, both for topical application and as injectable materials. The materials could have utilities in many biomedical applications, especially in the area of cardiovascular diseases and wound dressing.

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“…They have attracted considerable attention from chemists, materials and biomedicine scientists owing to their myriads of potential applications in many fields including tissue engineering, wearable devices, soft electronics, battery binders, etc. Among these versatile materials, self‐healing hydrogels, which can recover their original properties through autonomous healing after suffering from damages, exhibit an enormous potential in the fields of wound closure, scaffolds for tissue engineering, drug/cell delivery devices, and so on.…”

Section: Introductionmentioning

confidence: 99%

Tannin‐Tethered Gelatin Hydrogels with Considerable Self‐Healing and Adhesive Performances

Zhao

Long

et al. 2019

Macro Materials & Eng

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wearable devices, [4] soft electronics, [5,6] battery binders, [7][8][9] etc. Among these versatile materials, self-healing hydrogels, which can recover their original properties through autonomous healing after suffering from damages, exhibit an enormous potential in the fields of wound closure, [10,11] scaffolds for tissue engineering, [12,13] drug/cell delivery devices, [14][15][16] and so on.In nature, marine mussels can tightly attach to almost all surfaces by secreting mussel adhesive proteins (MAPs). [17] In addition, the adhesion property of MAPs is attributed to the presence of a special catechol-containing amino acid compound, 3,4-dihydroxyphenylalanine (DOPA). [18] The catechol groups of DOPA are easy oxidized to quinones in alkaline condition [1] and subsequently react with nucleophiles such as amines and thiols to form the 3D net structure of hydrogel via Schiff's base and Michael addition reactions. [19] Additionally, the catechol moieties endow DOPA with the capability to complex with various metal ions in order to produce coordination-crosslinked hydrogels. Owing to the versatility of DOPA, it has been coupled through various reactions to numerous macromolecules, including chitosan, [20] gelatin, [19] and polyethylene glycol (PEG). [21] This has allowed to fabricate mussel-inspired materials with self-healing and adhesive properties. The high price and potential neurotransmission effect of DOPA limit its commercial applications, however, and consequently the search of alternatives to DOPA is necessary. [22] Tannic acid (TA), a plant-derived polyphenolic compound, consists of a glucose core and ester-linked peripheral gallol groups (three adjacent hydroxyls attached to benzene). [23] With these functional groups, TA is capable to precipitate proteins (collagen and gelatin) by multi-point hydrogen bond and hydrophobic interactions. [24] The two adjacent phenolic hydroxyls of gallols in TA can also chelate metal ions (e.g., Fe 3+ , Al 3+ , Cr 3+ ) in the form of oxygen anion to form stable pentacyclic complexes. Although the third phenol hydroxyl is not involved in the formation of these pentacyclic structures, it can encourage the dissociation of the other two adjacent OH groups and accelerate the coordination reaction promoting its stability. [25] In addition, TA presents a good antioxidant capacity. The gallols of TA are oxidized to form quinones that further undergo nucleophilic Hydrogels Hydrogels, especially the ones with self-recovery and adhesive performances, have attracted more and more attention owing to their wide practical potential in the biomedical field involving cell delivery, wound filling, and tissue engineering. Tannic acid (TA), a nature-derived gallol-rich polyphenol, exhibits not only unique chelating properties with transition metal cations but also desirable anti-oxidation properties and strong bonding capability to proteins and gelatin. Thus, taking advantage of the versatility of TA, a one-pot method is proposed herein to produce TA-modified gelatin hydrogels with the aid ...

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Injectable and Tunable Gelatin Hydrogels Enhance Stem Cell Retention and Improve Cutaneous Wound Healing

Cited by 262 publications

References 66 publications

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Cytocompatible, Injectable, and Electroconductive Soft Adhesives with Hybrid Covalent/Noncovalent Dynamic Network

Tannin‐Tethered Gelatin Hydrogels with Considerable Self‐Healing and Adhesive Performances

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