Coauthored with Patrick McDaniel from HTL
One straightforward solution to overcoming the limitations caused by the HA’s fluidity and rapid degradation in vivo is to modify the hyaluronic acid with methacrylate. Methacrylated HA (HA-MA) allows the HA to be polymerized by free radicals via the addition of a photosensitive initiator. The resulting photocured, crosslinked hydrogel will have increased rigidity and be more resistant to degradation, even at low concentrations of 10% or less. With the enhanced rigidity, researchers can now bioprint, or otherwise fabricate, 3D structures and crosslink them with UV light immediately after gel deposition to maintain the shape. This makes HA-based scaffolds, organoids, cell culturing and disease models possible. The slower degradation time of the HA-MA hydrogels and structures also allows for sustained release drug delivery systems to be designed based on the degradation profile and the dosage of the drug vs. time. One bonus feature of the methacrylated HA gels is that everything from genes to cells to whole organisms can be encapsulated and protected from harsh physiological conditions in vivo.
When crosslinking via photopolymerization, the starting molecular weight of the HA should be optimized – less than 1000kDa is most common – but the dominant factor in determining the physical properties is the degree of substitution (DS). The higher the DS, the more vinyl conversions which leads to a higher degree of polymerization which means lower swelling ratios, slower degradation times and higher hydrogel shear moduli along with other rheological measurements. It’s worth noting, considering how the most popular use for methacrylated HA is to make 3D structures for live cells, that the DS of methacrylated HA does not affect cell attachment and proliferation.
The degree of substitution can range from low (<30%) to high (>60%). Below is a table of example methacrylated HA applications and the concentrations, molecular weight and DS:
|Scaffold for Intervertebral Disc Repair||400kDa||25%||1%|
|Hydrogel Scaffold for Tumor Modeling||300kDa||20-60%||10%|
|Hydrogel for Biologic Encapsulation||700kDa||94%||3%|
|Hydrogel for Wound Healing Dressing||70kDa||N/A||4%|
|Carrier for Stem Cell Delivery||400kDa||50%||1.5%|
In conclusion, methacrylated hyaluronic acid hydrogels offer a versatile platform for various in vitro applications. Their ability to mimic the natural microenvironment of tissues, coupled with their tunable properties, makes them valuable tools for tissue engineering, drug delivery, and stem cell research. As researchers continue to refine and expand their understanding of HA-MA hydrogels, their potential for advancing regenerative medicine and improving patient care becomes increasingly evident.
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