An official website of the United States government
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
A Quantitative Description for Designing the Extrudability of Shear‐Thinning Physical Hydrogels
Abstract Physically associated hydrogels (PHs) capable of reversible transitions between solid and liquid‐like states have enabled novel strategies for 3D printing, therapeutic drug and cell delivery, and regenerative medicine. Among the many design criteria (e.g., viscoelasticity, cargo diffusivity, biocompatibility) for these applications, engineering PHs for extrudability is a necessary and critical design criterion for the successful application of these materials. As the development of many distinct PH material systems continues, a strategy to determine the extrudability of PHs a priori will be exceedingly useful for reducing costly and time‐consuming trial‐and‐error experimentation. Here, a strategy to determine the property–function relationships for PHs in injectable drug delivery applications at clinically relevant flow rates is presented. This strategy—validated with two chemically and physically distinct PHs—reveals material design spaces in the form of Ashby‐style plots that highlight acceptable, application‐specific material properties. It is shown that the flow behavior of PHs does not obey a single shear‐thinning power law and the implications for injectable drug delivery are discussed. This approach for generating design criteria has potential for streamlining the screening of PHs and their utility in applications with varying geometrical (i.e., needle diameter) and process (i.e., flow rate) constraints.
more »
« less
- Award ID(s):
- 1760810
- PAR ID:
- 10453833
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Macromolecular Bioscience
- Volume:
- 21
- Issue:
- 2
- ISSN:
- 1616-5187
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell–cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell–cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.more » « less
-
Abstract Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion‐conducting membrane out to the local implanted area. This solvent‐flow‐free “dry” delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co‐ion is presented. By switching acetylcholine's associated co‐ion from chloride to carboxylate co‐ions as well as sulfopropyl acrylate‐based polyanions, steady‐state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices.more » « less
-
Abstract Fluorinated compounds, while rarely used by nature, are emerging as fundamental ingredients in biomedical research, with applications in drug discovery, metabolomics, biospectroscopy, and, as the focus of this review, peptide/protein engineering. Leveraging the fluorous effect to direct peptide assembly has evolved an entirely new class of organofluorine building blocks from which unique and bioactive materials can be constructed. Here, we discuss three distinct peptide fluorination strategies used to design and induce peptide assembly into nano‐, micro‐, and macro‐supramolecular states that potentiate high‐ordered organization into material scaffolds. These fluorine‐tailored peptide assemblies employ the unique fluorous environment to boost biofunctionality for a broad range of applications, from drug delivery to antibacterial coatings. This review provides foundational tactics for peptide fluorination and discusses the utility of these fluorous‐directed hierarchical structures as material platforms in diverse biomedical applications.more » « less
-
Abstract Hydrogels show great potential in biomedical applications due to their inherent biocompatibility, high water content, and resemblance to the extracellular matrix. However, they lack self‐powering capabilities and often necessitate external stimulation to initiate cell regenerative processes. In contrast, piezoelectric materials offer self‐powering potential but tend to compromise flexibility. To address this, creating a novel hybrid biomaterial of piezoelectric hydrogels (PHs), which combines the advantageous properties of both materials, offers a systematic solution to the challenges faced by these materials when employed separately. Such innovative material system is expected to broaden the horizons of biomedical applications, such as piezocatalytic medicinal and health monitoring applications, showcasing its adaptability by endowing hydrogels with piezoelectric properties. Unique functionalities, like enabling self‐powered capabilities and inducing electrical stimulation that mimics endogenous bioelectricity, can be achieved while retaining hydrogel matrix advantages. Given the limited reported literature on PHs, here recent strategies concerning material design and fabrication, essential properties, and distinctive applications are systematically discussed. The review is concluded by providing perspectives on the remaining challenges and the future outlook for PHs in the biomedical field. As PHs emerge as a rising star, a comprehensive exploration of their potential offers insights into the new hybrid biomaterials.more » « less
