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Abstract Injectable hydrogels are valuable tools in tissue engineering and regenerative medicine due to their unique advantages of injectability with minimal invasiveness and usability for irregularly shaped sites. However, it remains challenging to achieve scalable manufacturing together with matching physicochemical properties and on‐demand drug release for a high level of control over biophysical and biomedical cues to direct endogenous cells. Here, the use of an injectable fibro‐gel is demonstrated, a water‐filled network of entangled hydrogel microfibers, whose physicochemical properties and drug release profiles can be tailored to overcome these shortcomings. This fibro‐gel exhibits favorable in vitro biocompatibility and the capability to aid vascularization. The potential use of the fibro‐gel for advancing tissue regeneration is explored with a mice excision skin model. Preliminary in vivo tests indicate that the fibro‐gel promotes wound healing and new healthy tissue regeneration at a faster rate than a commercial gel. Moreover, it is demonstrated that the release of distinct drugs at different rates can further accelerate wound healing with higher efficiency, by using a two‐layer fibro‐gel model. The combination of injectability and tailorable properties of this fibro‐gel offers a promising approach in biomedical fields such as therapeutic delivery, medical dressings, and 3D tissue scaffolds for tissue engineering.
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Needle-injectable microcomposite cryogel scaffolds with antimicrobial properties
Abstract Porous three-dimensional hydrogel scaffolds have an exquisite ability to promote tissue repair. However, because of their high water content and invasive nature during surgical implantation, hydrogels are at an increased risk of bacterial infection. Recently, we have developed elastic biomimetic cryogels, an advanced type of polymeric hydrogel, that are syringe-deliverable through hypodermic needles. These needle-injectable cryogels have unique properties, including large and interconnected pores, mechanical robustness, and shape-memory. Like hydrogels, cryogels are also susceptible to colonization by microbial pathogens. To that end, our minimally invasive cryogels have been engineered to address this challenge. Specifically, we hybridized the cryogels with calcium peroxide microparticles to controllably produce bactericidal hydrogen peroxide. Our novel microcomposite cryogels exhibit antimicrobial properties and inhibit antibiotic-resistant bacteria (MRSA and Pseudomonas aeruginosa ), the most common cause of biomaterial implant failure in modern medicine. Moreover, the cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented activation of primary bone marrow-derived dendritic cells ex vivo. Finally, in vivo data suggested tissue integration, biodegradation, and minimal host inflammatory responses when the antimicrobial cryogels, even when purposely contaminated with bacteria, were subcutaneously injected in mice. Collectively, these needle-injectable microcomposite cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.
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- Award ID(s):
- 1847843
- PAR ID:
- 10219883
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 10
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Injectable hydrogels are attractive for therapeutic delivery because they can be locally administered through minimally-invasive routes. Charge-complementary peptide nanofibers provide hydrogels that are suitable for encapsulation of biotherapeutics, such as cells and proteins, because they assemble under physiological temperature, pH, and ionic strength. However, relationships between the sequences of charge-complementary peptides and the physical properties of the hydrogels that they form are not well understood. Here we show that hydrogel viscoelasticity, pore size, and pore structure depend on the pairing of charge-complementary “CATCH(+/−)” peptides. Oscillatory rheology demonstrated that co-assemblies of CATCH(4+/4−), CATCH(4+/6−), CATCH(6+/4−), and CATCH(6+/6−) formed viscoelastic gels that can recover after high-shear and high-strain disruption, although the extent of recovery depends on the peptide pairing. Cryogenic scanning electron microscopy demonstrated that hydrogel pore size and pore wall also depend on peptide pairing, and that these properties change to different extents after injection. In contrast, no obvious correlation was observed between nanofiber charge state, measured with ζ-potential, and hydrogel physical properties. CATCH(4+/6−) hydrogels injected into the subcutaneous space elicited weak, transient inflammation whereas CATCH(6+/4−) hydrogels induced stronger inflammation. No antibodies were raised against the CATCH(4+) or CATCH(6−) peptides following multiple challenges in vehicle or when co-administered with an adjuvant. These results demonstrate that CATCH(+/−) peptides form biocompatible injectable hydrogels with viscoelastic properties that can be tuned by varying peptide sequence, establishing their potential as carriers for localized delivery of therapeutic cargoes.more » « less
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null (Ed.)Abstract Current materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.more » « less
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Abstract Dynamic covalent chemistry (DCC) crosslinks can form hydrogels with tunable mechanical properties permissive to injectability and self‐healing. However, not all hydrogels with transient crosslinks are easily extrudable. For this reason, two additional design parameters must be considered when formulating DCC‐crosslinked hydrogels: 1) degree of functionalization (DoF) and 2) polymer molecular weight (MW). To investigate these parameters, hydrogels comprised of two recombinant biopolymers: 1) a hyaluronic acid (HA) modified with benzaldehyde and 2) an elastin‐like protein (ELP) modified with hydrazine (ELP‐HYD), are formulated. Several hydrogel families are synthesized with distinct HA MW and DoF while keeping the ELP‐HYD component constant. The resulting hydrogels have a range of stiffnesses,G′ ≈ 10–1000 Pa, and extrudability, which is attributed to the combined effects of DCC crosslinks and polymer entanglements. In general, lower MW formulations require lower forces for injectability, regardless of stiffness. Higher DoF formulations exhibit more rapid self‐healing. Gel extrusion through a cannula (2 m length, 0.25 mm diameter) demonstrates the potential for minimally invasive delivery for future biomedical applications. In summary, this work highlights additional parameters that influence the injectability and network formation of DCC‐crosslinked hydrogels and aims to guide future design of injectable hydrogels.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41598-020-75196-1
