Shear‐thinning hydrogels are useful for biomedical applications, from 3D bioprinting to injectable biomaterials. Although they have the appropriate properties for injection, it may be advantageous to decouple injectability from the controlled release of encapsulated therapeutics. Toward this, composites of hydrogels and encapsulated microgels are introduced with microgels that are fabricated via microfluidics. The microgel cross‐linker controls degradation and entrapped molecule release, and the concentration of microgels alters composite hydrogel rheological properties. For the treatment of myocardial infarction (MI), interleukin‐10 (IL‐10) is encapsulated in microgels and released from composites. In a rat model of MI, composites with IL‐10 reduce macrophage density after 1 week and improve scar thickness, ejection fraction, cardiac output, and the size of vascular structures after 4 weeks when compared to saline injection. Improvements are also observed with the composite without IL‐10 over saline, emphasizing the role of injectable hydrogels alone on tissue repair.
- Award ID(s):
- 1705852
- Publication Date:
- NSF-PAR ID:
- 10067122
- Journal Name:
- Biomaterials Science
- Volume:
- 6
- Issue:
- 8
- Page Range or eLocation-ID:
- 2073 to 2083
- ISSN:
- 2047-4830
- Sponsoring Org:
- National Science Foundation
More Like this
-
Abstract -
Abstract Biomaterials are key factors in regenerative medicine. Matrices used for cell delivery are especially important, as they provide support to transplanted cells that is essential for promoting cell survival, retention, and desirable phenotypes. Injectable matrices have become promising and attractive due to their minimum invasiveness and ease of use. Conventional injectable matrices mostly use hydrogel precursor solutions that form solid, cell‐laden hydrogel scaffolds in situ. However, these materials are associated with challenges in biocompatibility, shear‐induced cell death, lack of control over cellular phenotype, lack of macroporosity and remodeling, and relatively weak mechanical strength. This Progress Report provides a brief overview of recent progress in developing injectable matrices to overcome the limitations of conventional in situ hydrogels. Biocompatible chemistry and shear‐thinning hydrogels have been introduced to promote cell survival and retention. Emerging investigations of the effects of matrix properties on cellular function in 3D provide important guidelines for promoting desirable cellular phenotypes. Moreover, several novel approaches are combining injectability with macroporosity to achieve macroporous, injectable matrices for cell delivery.
-
Anisotropic Rod‐Shaped Particles Influence Injectable Granular Hydrogel Properties and Cell Invasion
Abstract Granular hydrogels have emerged as a new class of injectable and porous biomaterials that improve integration with host tissue when compared to solid hydrogels. Granular hydrogels are typically prepared using spherical particles and this study considers whether particle shape (i.e., isotropic spheres vs anisotropic rods) influences granular hydrogel properties and cellular invasion. Simulations predict that anisotropic rods influence pore shape and interconnectivity, as well as bead transport through granular assemblies. Photo‐cross‐linkable norbornene‐modified hyaluronic acid is used to produce spherical and rod‐shaped particles using microfluidic droplet generators and formed into shear‐thinning and self‐healing granular hydrogels, with particle shape influencing mechanics and injectability. Rod‐shaped particles form granular hydrogels that have anisotropic and interconnected pores, with pore size and number influenced by particle shape and degree of packing. Robust in vitro sprouting of endothelial cells from embedded cellular spheroids is observed with rod‐shaped particles, including higher sprouting densities and sprout lengths when compared to hydrogels with spherical particles. Cell and vessel invasion into granular hydrogels when injected subcutaneously in vivo are significantly greater with rod‐shaped particles, whereas a gradient of cellularity is observed with spherical particles. Overall, this work demonstrates potentially superior functional properties of granular hydrogels with rod‐shaped particles for tissue repair.
-
Abstract When properly deployed, the immune system can eliminate deadly pathogens, eradicate metastatic cancers, and provide long‐lasting protection from diverse diseases. Unfortunately, realizing these remarkable capabilities is inherently risky as disruption to immune homeostasis can elicit dangerous complications or autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body. Here, this study explored the ability of a slow‐releasing injectable hydrogel depot to reduce dose‐limiting toxicities of immunostimulatory CD40 agonist (CD40a) while maintaining its potent anticancer efficacy. A previously described polymer‐nanoparticle (PNP) hydrogel system is leveraged that exhibits shear‐thinning and yield‐stress properties that are hypothesized to improve locoregional delivery of CD40a immunotherapy. Using positron emission tomography, it is demonstrated that prolonged hydrogel‐based delivery redistributes CD40a exposure to the tumor and the tumor draining lymph node (TdLN), thereby reducing weight loss, hepatotoxicity, and cytokine storm associated with standard treatment. Moreover, CD40a‐loaded hydrogels mediate improved local cytokine induction in the TdLN and improve treatment efficacy in the B16F10 melanoma model. PNP hydrogels, therefore, represent a facile, drug‐agnostic method to ameliorate immune‐related adverse effects and explore locoregional delivery of immunostimulatory drugs.
-
Abstract Injectable 3D cell scaffolds possessing both electrical conductivity and native tissue‐level softness would provide a platform to leverage electric fields to manipulate stem cell behavior. Granular hydrogels, which combine jamming‐induced elasticity with repeatable injectability, are versatile materials to easily encapsulate cells to form injectable 3D niches. In this work, it is demonstrated that electrically conductive granular hydrogels can be fabricated via a simple method involving fragmentation of a bulk hydrogel made from the conducting polymer PEDOT:PSS. These granular conductors exhibit excellent shear‐thinning and self‐healing behavior, as well as record‐high electrical conductivity for an injectable 3D scaffold material (≈10 S m−1). Their granular microstructure also enables them to easily encapsulate induced pluripotent stem cell (iPSC)‐derived neural progenitor cells, which are viable for at least 5 d within the injectable gel matrices. Finally, gel biocompatibility is demonstrated with minimal observed inflammatory response when injected into a rodent brain.