Blended and Microparticle Composite Hyaluronan Hydrogels with Programmable Degradation through Selective Oxidation

TL;DR

This paper introduces a new type of hyaluronan hydrogel that can be programmed to degrade in different ways, depending on its composition.

Contribution

A novel strategy for programmable degradation in hyaluronan hydrogels using blended and microparticle composite networks.

Findings

Blended hydrogels maintain viscoelastic properties while allowing tunable degradation rates.

Hydrogel microparticle composites exhibit abrupt fragmentation upon degradation.

Degradation modes can be programmed by adjusting the oTHA-to-THA ratio.

Abstract

The design space
of hydrogels for biomedical applications
embraces
a wide variety of parameters that can be tuned through chemical modification.
Among them, tissue adhesion and viscoelastic properties contribute
to the integration of tissue-engineered constructs with native tissues,
while the degradation profile determines their temporal evolution
and cell invasion. Selective 1,2-diol oxidation is a versatile tool
to control all of these properties in polysaccharide-based hydrogels
by generating aldehyde groups. A key challenge in implementing this
tool is that although aldehyde groups improved adhesion, they also
promoted chain fragmentation, demanding a trade-off. To address this,
we devised a strategy that leverages the adhesiveness of oxidized
biopolymers together with the mechanical stability of their nonoxidized
counterparts. Here, we synthesized tyramine-modified hyaluronan (THA)
and its oxidized form (oTHA) and evaluated their degradation and adhesion
in various combinations and formats, including blended hydrogels and hydrogel microparticle composite networks.
As the degree of oxidation increased in oTHA, its molecular weight
decreased, the storage modulus of the resulting hydrogels slightly
declined, brittleness increased, and physical degradation accelerated.
These opposing properties were finely offset in two-component blended
hydrogels; increasing the oTHA content proportionally accelerated
the degradation rate in both bulk and hydrogel microparticle composite
formats while maintaining consistent viscoelastic properties and network
topology at a fixed total polymer concentration. By adjusting the
oTHA-to-THA ratio, we generated composite hydrogels with two distinct
degradation behaviors: (i) collapse-type mode, where blended hydrogels gradually softened and spread without
fragmenting; and (ii) fragmentation-type mode, where hydrogel microparticle composites abruptly broke into discrete
pieces over degradation time. This tunability enables the design of
a new class of composite soft biomaterials with programmable degradation.
Such materials show potential for tunable tissue engineering strategies,
which could be implemented for controlling cell invasion, migration,
and proliferation in biological applications.

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