Enabling Surgical Placement of Hydrogels Through Achieving Paste-Like Rheological Behavior in Hydrogel Precursor Solutions

Abstract

Hydrogels are a promising class of materials for tissue regeneration, but they lack the ability to be molded into a defect site by a surgeon because hydrogel precursors are liquid solutions that are prone to leaking during placement. Therefore, although the main focus of hydrogel technology and developments are on hydrogels in their crosslinked form, our primary focus is on improving the fluid behavior of hydrogel precursor solutions. In this work, we introduce a method to achieve paste-like hydrogel precursor solutions by combining hyaluronic acid nanoparticles with traditional crosslinked hyaluronic acid hydrogels. Prior to crosslinking, the samples underwent rheological testing to assess yield stress and recovery using linear hyaluronic acid as a control. The experimental groups containing nanoparticles were the only solutions that exhibited a yield stress, demonstrating that the nanoparticulate rather than the linear form of hyaluronic acid was necessary to achieve paste-like behavior. The gels were also photocrosslinked and further characterized as solids, where it was demonstrated that the inclusion of nanoparticles did not adversely affect the compressive modulus and that encapsulated bone marrow-derived mesenchymal stem cells remained viable. Overall, this nanoparticle-based approach provides a platform hydrogel system that exhibits a yield stress prior to crosslinking, and can then be crosslinked into a hydrogel that is capable of encapsulating cells that remain viable. This behavior may hold significant impact for hydrogel applications where a paste-like behavior is desired in the hydrogel precursor solution.

Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

“…6A). There was no significant difference between the MeHA + 10% DCC + TGF-b 3 and MeHA + DVC groups, however. At 3 weeks after crosslinking, the MeHA + DVC group had a DNA content of 386 -73 ng DNA per gel, which was 36%, 49%, and 35% less than the DNA content of the MeHA + TGF-b 3 , MeHA + 5% DCC, and MeHA + 10% DCC + TGFb 3 groups, respectively ( p < 0.05) (Fig.…”

“…4), which was 3.5, 2.2, and 1.8 times larger than the compressive moduli of MeHA, MeHA + 5% DCC, and MeHA + 10% DCC groups, respectively ( p < 0.05). Furthermore, the modulus of the MeHA + DVC group was 2.3 and 1.7 times larger than that of the MeHA + TGF-b 3 and MeHA + 10% DCC + TGF-b 3 groups, respectively. Finally, the moduli of the MeHA + DVC and MeHA + TGF-b 3 groups were 1.7 and 1.6 times, respectively, larger than those of their acellular controls ( p < 0.05).…”

“…At day 1 after crosslinking, the MeHA + 10% DCC group had 570 -130 ng DNA per gel, and the only gels with a significantly different DNA content from this group were the MeHA + 10% DCC + TGF-b 3 and MeHA + DVC groups, which had DNA contents 45% and …”

“…In addition, another objective was to observe how DVC and DCC affected the rheology of the hydrogel precursors. We hypothesized that a paste-like material composed of DVC would induce superior chondrogenesis compared with that of DCC and compared with hydrogels exposed to TGF-b 3 or the combination of DCC and TGF-b 3 over the 6-week period.…”

“…1,2 To overcome this drawback, we recently introduced a method to achieve paste-like hydrogel precursor solutions by combining hyaluronic acid nanoparticles with traditional crosslinked hyaluronic acid hydrogels, where the paste-like behavior was induced by the presence of the hyaluronic acid nanoparticles. 3 These hyaluronic acid formulations were then crosslinked to form a rigid traditional hydrogel structure. In an effort to introduce bioactivity to the material, in this study we substituted the hyaluronic acid nanoparticles for particles made from naturally derived cartilage extracellular matrix (ECM).…”