Stem cells have shown substantial promise for various diseases in preclinical and clinical trials. However, low cell engraftment rates significantly limit the clinical translation of stem cell therapeutics. Numerous injectable hydrogels have been developed to enhance cell retention. Yet, the design of an ideal material with tunable properties that can mimic different tissue niches and regulate stem cell behaviors remains an unfulfilled promise. Here, an injectable poly(ethylene glycol) (PEG)-gelatin hydrogel is designed with highly tunable properties, from a multifunctional PEG-based hyperbranched polymer and a commercially available thiolated gelatin. Spontaneous gelation occurs within about 2 min under the physiological condition. Murine adiposederived stem cells (ASCs) can be easily encapsulated into the hydrogel, which supports ASC growth and maintains their stemness. The hydrogel mechanical properties, biodegradability, and cellular responses can be finely controlled by changing hydrogel formulation and cell seeding densities. An animal study shows that the in situ formed hydrogel significantly improves cell retention, enhances angiogenesis, and accelerates wound closure using a murine wound healing model. These data suggest that injectable PEG-gelatin hydrogel can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications.

Controlled/living radical polymerization (CRP) is a widely used technique that allows the synthesis of defined polymer architectures through precise control of molecular weights and distributions. However, the architectures of polymers prepared by the CRP techniques are limited to linear, cross-linked, and branched/dendritic structures. Here, we report the preparation of a new 3D single cyclized polymer chain structure from an in situ deactivation enhanced atom transfer radical polymerization of multivinyl monomers (MVMs), which are conventionally used for the production of branched/cross-linked polymeric materials as defined by P. Flory and W. Stockmayer nearly 70 years ago. We provide new evidence to demonstrate that it is possible to kinetically control both the macromolecular architecture and the critical gelling point in the polymerization of MVMs, suggesting the classical Flory-Stockmayer mean field theory should be supplemented with a new kinetic theory based on the space and instantaneous growth boundary concept.

Diabetic wounds, which are a severe type of diabetes, have become one of the most serious clinical problems. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholic drug-Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment.

1A series of hyperbranched poly(β-amino ester) polymers have been synthesized via a Michael addition approach for the fabrication of hydrogels for wound healing.

Stimuli-responsive color-changing hydrogels, commonly colored using embedded photonic crystals (PCs), have potential applications ranging from chemical sensing to camouflage and anti-counterfeiting. A major limitation in these PC hydrogels is that they require significant deformation (>20%) in order to change the PC lattice constant and generate an observable chromatic shift (∼100 nm). By analyzing the mechanism of how chameleon skin changes color, we developed a strain-accommodating smart skin (SASS), which maintains near-constant size during chromatic shifting. SASS is composed of two types of hydrogels: a stimuli-responsive, PC-containing hydrogel that is patterned within a second hydrogel with robust mechanical properties, which permits strain accommodation. In contrast to conventional “accordion”-type PC responsive hydrogels, SASS maintains near-constant volume during chromatic shifting. Importantly, SASS materials are stretchable (strain ∼150%), amenable to patterning, spectrally tunable, and responsive to both heat and natural sunlight. We demonstrate examples of using SASS for biomimicry. Our strategy, to embed responsive materials within a mechanically matched scaffolding polymer, provides a general framework to guide the future design of artificial smart skins.

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IntroductionCell therapy using adipose-derived stem cells has been reported to improve chronic wounds via differentiation and paracrine effects. One such strategy is to deliver stem cells in hydrogels, which are studied increasingly as cell delivery vehicles for therapeutic healing and inducing tissue regeneration. This study aimed to determine the behaviour of encapsulated adipose-derived stem cells and identify the secretion profile of suitable growth factors for wound healing in a newly developed thermoresponsive PEG–hyaluronic acid (HA) hybrid hydrogel to provide a novel living dressing system.MethodsIn this study, human adipose-derived stem cells (hADSCs) were encapsulated in situ in a water-soluble, thermoresponsive hyperbranched PEG-based copolymer (PEGMEMA–MEO2MA–PEGDA) with multiple acrylate functional groups in combination with thiolated HA, which was developed via deactivated enhanced atom transfer radical polymerisation of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, Mn = 475), 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and poly(ethylene glycol) diacrylate PEGDA (Mn = 258). hADSCs embedded in the PEGMEMA–MEO2MA–PEGDA and HA hybrid hydrogel system (P-SH-HA) were monitored and analysed for their cell viability, cell proliferation and secretion of growth factors (vascular endothelial growth factor, transforming growth factor beta and placental-derived growth factor) and cytokines (IFNγ, IL-2 and IL-10) under three-dimensional culture conditions via the ATP activity assay, alamarBlue® assay, LIVE/DEAD® assay and multiplex ELISA, respectively.ResultshADSCs were successfully encapsulated in situ with high cell viability for up to 7 days in hydrogels. Although cellular proliferation was inhibited, cellular secretion of growth factors such as vascular endothelial growth factor and placental-derived growth factor production increased over 7 days, whereas IL-2 and IFNγ release were unaffected.ConclusionThis study indicates that hADSCs can be maintained in a P-SH-HA hydrogel, and secrete pro-angiogenic growth factors with low cytotoxicity. With the potential to add more functionality for further structural modifications, this stem cell hydrogel system can be an ideal living dressing system for wound healing applications.

A well-defined poly(ethylene glycol) based hyperbranched thermoresponsive copolymer with high content of acrylate vinyl groups was synthesized via a "one-pot and one-step" deactivation enhanced atom transfer radical polymerization approach, which provided an injectable and in situ crosslinkable system via Michael-type thiol-ene reaction with a thiol-modified hyaluronan biopolymer. The hyperbranched structure, molecular weight, and percentage of vinyl content of the copolymer were characterized by gel permeation chromatography and (1)H NMR. The lower critical solution temperature of this copolymer is close to body temperature, which can result in a rapid thermal gelation at 37 °C. The scanning electron microscopy analysis of crosslinked hydrogel showed the network formation with porous structure, and 3D cell culture study demonstrated the good cell viability after the cells were embedded inside the hydrogel. This injectable and in situ crosslinking hybrid hydrogel system offers great promise as a new class of hybrid biomaterials for tissue engineering.