Macroporous StarPEG-Heparin Cryogels

Abstract

Macroporous scaffolds with adaptable mechanical and biomolecular properties can be instrumental in enabling cell-based therapies. To meet these requirements, a cryostructuration method was adapted to prepare spongy hydrogels based on chemically cross-linked star-shaped poly(ethylene glycol) (starPEG) and heparin. Subzero temperature treatment of the gel forming reaction mixtures and subsequent lyophilization of the incompletely frozen gels resulted in macroporous biohybrid cryogels showing rapid swelling, porosity of up to 92% with interconnected large pores (30–180 μm), low bulk stiffness, and high mechanical stability upon compression. The applicability of the cryogel scaffolds was investigated using human umbilical vein endothelial cells. Cell attachment and three-dimensional spreading resulted in evenly distributed viable cells within the macroporous starPEG-heparin materials, demonstrating the significant translational potential of the developed three-dimensional cell carriers.

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

“…[62] Macroporous hydrogel materials are synthesized utilizing different techniques, such as particle leaching, freeze-drying, gas foaming and electrospinning. Cryogelation (a freeze-drying-based technique) of the biohybrid starPEG-HEP hydrogels allowed the creation of interconnected porosity within these materials [63] (see Figure 5C and D). Here, ice crystals formed by the treatment of an aqueous gel-forming reaction mixture at subzero temperatures acted as a porogen that was subsequently lyophilized, leading to a homogeneous interconnected pore structure with an average diameter of 30-50 μm (see Figure 5D).…”

“…Furthermore, the unique properties of strong local stiffness but bulk compliance lead to high compressibility of cryogel materials: cryogels can be compressed without a significant increase in modulus until the strain is equal to the porosity of the materials (approximately 90%); see [63] . Capitalizing on this unique feature allows applications as a shape-memory material.…”

“…D) Left: Confocal laser scanning micrograph of Alexa ® 488 (green)-labeled cryogels swollen in phosphate-buffered saline. Right: Scanning electron micrograph of a dry cryogel, reproduced with permission from [63] , copyright ACS Publications 2012.…”

Cryotemplation for the rapid fabrication of porous, patternable photopolymerized hydrogels

“…Percent compression at yield was similar under these conditions and averaged 34.0% deformation. Young’s moduli and compressive strengths using our fabrication process were found to be comparable to porous hydrogels fabricated using cryogelation methods 37, 49–55 . Molecular weight had the greatest impact on the mechanical properties, as the low molecular weight polymer had a modulus (16.4 ± 1.4 kPa, Figure 3a) and ultimate strength (3.42 ± 0.2 kPa, Figure 3b) that was approximately an order of magnitude greater than that for the high molecular weight polymer.…”

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

“…Semi-synthetic biomaterial scaffolds can be produced by combining these natural biopolymers with synthetic polymers such as PEG, with the aim of representing or mimicking host tissue more closely [53,54], allowing cellular attachment [24], introducing enzyme cleavability [55], or improving the binding of growth factors [56]. These semi-synthetic materials are often designed in such a way that a functionalized PEG molecule (often branched) is used to crosslink the biopolymer either via an intrinsically present amine [57], via EDC/NHS activated carboxyl groups [58], or via a previously added functional group [59].…”