Experimental optimization of an in situ forming hydrogel for hemorrhage control

Abstract

The fabrication of a novel in situ forming hydrogel composed of a multifunctional poly(ethylene glycol) (PEG) N-hydroxysuccinimide ester (NHS) and poly(allylamine hydrochloride) (PAA) was investigated. FTIR confirmed that PAA formed the hydrogel matrix (i.e., the formation of a PAA-like hydrogel). A factorial experiment was conducted to identify the key parameters that controlled gelation time, gel content, and swelling properties. The type of PEG (e.g., 4- and 6-arm) appeared to play a major role in determining all three performance parameters, with the greatest effect on gelation time. Other influencing factors include (a) the PEG concentration, which contributes to the gelation time and gel content; (b) pH of the buffer used for dissolving each polymer, which can affect the gelation time; and (c) PAA molecular weights, which contribute to the gel content and swelling. The concentration of PAA solution had no significant effects on hydrogel formation and properties within the investigated range, presumably due to negligible changes in the crosslinking density of the hydrogels. The PAA buffer pH influenced the gel content as well. Finally, thromboelastography was used to examine the effects of each polymer and their in situ gelation on blood coagulation in vitro. All individual polymers tested reduced clot strength, while the gelation of the polymers enhanced overall procoagulant effects. These results suggest that the biomaterial can be optimized to provide a combination of rapid gelation and swelling properties suitable for hemorrhage control and thus warrant further studies in animal bleeding models.

Hemostatic strategies for traumatic and surgical bleeding

“…Utilizing the Schiff‐base reaction (Fig. ), the two mixtures polymerize upon application . This material reduced clotting time and improved clot strength as measured using thrombelastography, but hemostatic efficacy was not evaluated in vivo .…”

“…In situ forming synthetic tissue sealants are materials that transition from a liquid to a solid or gel state through physical or chemical crosslinking in a localized site . Physical crosslinks may be initiated through temperature‐responsive gelation or ionic charge interactions .…”

One-pot preparation of ultrastrong double network hydrogels

“…There have been constant efforts to improve the functionality of the hydrogels such as bioactivity [16,17], absorption properties for heavy metal ions and dye [18] and etc. However, the mechanical properties of conventional PEG and PAA hydrogels are mostly off target because both of PEG and PAA networks are relatively fragile, so neither would be expected to make the sole contribution to mechanical enhancement [14]. PEG/PAA IPN hydrogels were prepared by a (two-step) sequential free radical polymerization in order of end-linked PEG-diacrylate macromonomers and loosely crosslinked PAA to realize high mechanical strength of 9.7 MPa (water content was unkown) [11].…”

“…Polyacrylic acid (PAA) and polyethylene glycol (PEG) are used as the preferred polymers in preparation of biomedical hydrogels because they are safe and easily available [14,15]. There have been constant efforts to improve the functionality of the hydrogels such as bioactivity [16,17], absorption properties for heavy metal ions and dye [18] and etc.…”

Standardized methods to quantify thrombogenicity of blood‐contacting materials via thromboelastography

“…This group however failed to observe any significant changes in the TEG parameters when compared to saline treated controls. 21 Similarly Peng et al 26 synthesized hydrogels and mixed the gel with the blood in the TEG cups before performing the analysis. Alternately Chepurov et al 27 incubated whole blood in hydrogel tubes for 1 hr before aliquoting the blood into the TEG cups.…”