Addition of perfluorocarbons to alginate hydrogels significantly impacts molecular transport and fracture stress

Abstract

Perfluorocarbons (PFCs) are used in biomaterial formulations to increase oxygen (O(2) ) tension and create a homogeneous O(2) environment in three-dimensional tissue constructs. It is unclear how PFCs affect mechanical and transport properties of the scaffold, which are critical for robustness, intracellular signaling, protein transport, and overall device efficacy. In this study, we investigate composite alginate hydrogels containing a perfluorooctyl bromide (PFOB) emulsion stabilized with Pluronic(®) F68 (F68). We demonstrate that PFC addition significantly affects biomaterial properties and performance. Solution and hydrogel mechanical properties and transport of representative hydrophilic (riboflavin), hydrophobic (methyl and ethyl paraben), and protein (bovine serum albumin, BSA) solutes were compared in alginate/F68 composite hydrogels with or without PFOB. Our results indicate that mechanical properties of the alginate/F68/PFOB hydrogels are not significantly affected under small strains, but a significant decrease fracture stress is observed. The effective diffusivity D(eff) of hydrophobic small molecules decreases with PFOB emulsion addition, yet the D(eff) of hydrophilic small molecules remained unaffected. For BSA, the D(eff) increased and the loading capacity decreased with PFOB emulsion addition. Thus, a trade-off between the desired increased O(2) supply provided by PFCs and the mechanical weakening and change in transport of cellular signals must be carefully considered in the design of biomaterials containing PFCs.

Figure 1

The hydrogel system investigated in this work is comprised of 1% w/v alginate solution which contains a perfluorocarbon (perfluorooctyl bromide, PFOB) and a non-ionic surfactant (Pluronic^® F68) at varying concentrations. Hydrogels are formed by internal crosslinking with 50 mM CaEDTA, which is hydrolyzed by 50 mM GDL. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONSWILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.

Figure 2

Representative experimental release data for riboflavin (●) and methyl paraben (▪) and corresponding model fits from 1% alginate/2% F68/10% PFOB composite hydrogels. All % values are in w/v. © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONSWILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.

Figure 3

Average particle size of F68/PFOB emulsions is concentration dependent. Average diameter of F68/PFOB emulsions decrease in increasing F68, but increase with increasing PFOB. 10% PFOB emulsions (∆) show the largest particle size, followed by 7% PFOB (○) and 5% PFOB (□). All % values are in w/v. Error is reported as the standard deviation across all samples taken. © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONSWILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.

Figure 4

Shear modulus of alginate/F68/PFOB composite matrices. (a) Representative plot of storage (G′, filled symbols) and loss (G″, open symbols) moduli as a function of oscillation frequency. Both G′ and G″ show a weak frequency dependence. Alginate/2% F68 (▪, □) and alginate/2% F68/5% PFOB (●, ○) have similar profiles (n = 4). (b) Storage modulus at a frequency of 1 Hz. Comparison is made to show statistical similarity amongst alginate hydrogels containing F68/PFOB emulsions (p > 0.05, n = 4). All % values are in w/v.

Figure 5

Fracture stress from uniaxial compression, compressed at a strain rate of 10%/min. The 10% PFOB formulations show lower fracture stress than alginate/F68 composite hydrogels. (*) denotes statistical difference from the appropriate F68 control sample (p ≤ 0.05, n ≥ 4). All % values are in w/v. © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONSWILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.

Figure 6

Scanning electron micrographs (SEM) of alginate/F68/PFOB composite matrices shows no significant change in mesh size with the addition of PFOB. (a) 1% alginate/1% F68. (b) 1% alginate/1% F68/5% PFOB. (c) 1% alginate/1% F68/10% PFOB. All % values are in w/v. © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONSWILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.