Non‐Newtonian Polymer–Nanoparticle Hydrogels Enhance Cell Viability during Injection

Abstract

Drug delivery and cell transplantation require minimally invasive deployment strategies such as injection through clinically relevant high‐gauge needles. Supramolecular hydrogels comprising dodecyl‐modified hydroxypropylmethylcellulose and poly(ethylene glycol)‐block‐poly(lactic acid) have been previously demonstrated for the delivery of drugs and proteins. Here, it is demonstrated that the rheological properties of these hydrogels allow for facile injectability, an increase of cell viability after injection when compared to cell viabilities of cells injected in phosphate‐buffered saline, and homogeneous cell suspensions that do not settle. These hydrogels are injected at 1 mL min−1 with pressures less than 400 kPa, despite the solid‐like properties of the gel when at rest. The cell viabilities immediately after injection are greater than 86% for adult human dermal fibroblasts, human umbilical vein cells, smooth muscle cells, and human mesenchymal stem cells. Cells are shown to remain suspended and proliferate in the hydrogel at the same rate as observed in cell media. The work expands on the versatility of these hydrogels and lays a foundation for the codelivery of drugs, proteins, and cells.

Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

“…Tailored-made hydrogels enable the incorporation of specific bioactive epitopes [21] and exhibit physical properties, such as non-Newtonian behavior to facilitate injectability. [22] However, the use of injectable hydrogels in maxillofacial surgery is limited and in most cases hydrogels have been used mainly as a delivery vehicle for growth factors, such as bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). [23][24][25] Furthermore, while growth factors are efficient promoters of tissue growth, their use is associated with a variety of critical complications, such as the need for large amounts of growth factors due to the rapid inactivation and clearance of the growth factors, [26] high-costs, and uncontrolled activity.…”

Injectable supramolecular polymer–nanoparticle hydrogels enhance human mesenchymal stem cell delivery

“…13 Additionally hydrogels can act as immunomodulatory protective barriers against infiltrating immune cells. 16,[18][19][20][21][22][23] Injectable hydrogels enhance cell viability during the injection process compared to liquid vehicles by alleviating the mechanical forces cells experience when traveling through small diameter needles. 10,15,16 Yet, crosslinked hydrogels containing cells often require invasive implantation procedures.…”

“…14 The benefits of encapsulating hMSCs in hydrogels have been shown in multiple clinical studies targeting an array of indications. 19,23 However, injectable shearthinning hydrogels are often formed through weak physical interactions and cannot persist long enough in the body to enhance cell retention compared to traditional liquid injections. 17 The development of shear-thinning hydrogels has enabled quicker, less invasive administration procedures by injection through a needle.…”

“…16,[18][19][20][21][22][23] Injectable hydrogels enhance cell viability during the injection process compared to liquid vehicles by alleviating the mechanical forces cells experience when traveling through small diameter needles. 19,23 However, injectable shearthinning hydrogels are often formed through weak physical interactions and cannot persist long enough in the body to enhance cell retention compared to traditional liquid injections. 21 To circumvent this challenge, researchers have developed stimuli responsive and dynamic hydrogel materials that change properties in situ after injection.…”

Supramolecular Hydrogels for Biomedical Applications

“…Research from Appel and colleagues next describes a different approach to the generation of nanocomposite materials through the creation of polymer‐nanoparticle hydrogels. [19] Hydrophobic interactions between C 12 ‐modified hydroxypropylmethylcellulose and PEG‐b‐PLA nanoparticles result in three‐dimensional hydrogel networks amenable to the delivery of a variety of therapeutic payloads. In this work, hydrogels are evaluated for the encapsulation and delivery of several different cell types, with no impact on cell viability or proliferation arising from extrusion of cells within the hydrogels.…”