“…In support of our arguments on the mode of action, fibroblast differentiation at low TGFβ1 levels was already discussed in the literature for another GAG-containing bulk hydrogel system, however, without showing supporting data 12 . Furthermore, we want to discuss an additional option for the operational mode of our system.…”
Section: Resultssupporting
confidence: 85%
“…2C) show that variation of loading concentrations permits control of concentrations of bound cytokine in the µ-beads and consequently the release of TGFβ1 into the medium. Such a control of TGFβ1 release was also found in another heparin-based layered hydrogel system 12 .Figure 2TGFβ1 is bound and released by µ-beads. ( A ) Modification of porous agarose µ-beads with GAG is achieved by reaction in presence of EDC, enabling formation of covalent bonds between GAG’s acidic groups and amine groups of µ-beads.…”
TGFβ1 is a key regulator for induction of tissue remodeling after dermal wounding. We present a model of paracrine delivery of TGFβ1 for differentiation of dermal fibroblasts based on a fibrillar 3D collagen matrix and embedded TGFβ1 releasing microparticles. We found differentiation into myofibroblasts was achieved in a TGFβ1 dependent manner at much lower doses than systemic delivery. This effect is accounted to the slow and sustained TGFβ1 release mimicking paracrine cell signals.
“…In support of our arguments on the mode of action, fibroblast differentiation at low TGFβ1 levels was already discussed in the literature for another GAG-containing bulk hydrogel system, however, without showing supporting data 12 . Furthermore, we want to discuss an additional option for the operational mode of our system.…”
Section: Resultssupporting
confidence: 85%
“…2C) show that variation of loading concentrations permits control of concentrations of bound cytokine in the µ-beads and consequently the release of TGFβ1 into the medium. Such a control of TGFβ1 release was also found in another heparin-based layered hydrogel system 12 .Figure 2TGFβ1 is bound and released by µ-beads. ( A ) Modification of porous agarose µ-beads with GAG is achieved by reaction in presence of EDC, enabling formation of covalent bonds between GAG’s acidic groups and amine groups of µ-beads.…”
TGFβ1 is a key regulator for induction of tissue remodeling after dermal wounding. We present a model of paracrine delivery of TGFβ1 for differentiation of dermal fibroblasts based on a fibrillar 3D collagen matrix and embedded TGFβ1 releasing microparticles. We found differentiation into myofibroblasts was achieved in a TGFβ1 dependent manner at much lower doses than systemic delivery. This effect is accounted to the slow and sustained TGFβ1 release mimicking paracrine cell signals.
“…To achieve this functionality within a hydrogel, a specially designed linker moiety typically sensitive to an enzyme can be copolymerized into the hydrogel so as to allow for localized protease-mediated degradation of the polymeric network (79). In combination with a growth factor-sequestering component, these cell-instructive hydrogel matrices are able to reversibly immobilize growth factors on demand (81). The concept of protease-mediated degradation has been recently taken a step forward by implementing a negative feedback loop through a combinatory effect of an enzyme-labile moiety and an enzyme inhibitor coembedded in the hydrogel matrix (80).…”
Hydrogels are formed from hydrophilic polymer chains surrounded by a water-rich environment. They have widespread applications in various fields such as biomedicine, soft electronics, sensors, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. Further, the lack of dynamic cues and structural complexity within the hydrogels has limited their functions. Recent developments include engineering hydrogels that possess improved physicochemical properties, ranging from designs of innovative chemistries and compositions to integration of dynamic modulation and sophisticated architectures. We review major advances in designing and engineering hydrogels and strategies targeting precise manipulation of their properties across multiple scales.
“…[4a] Based on this property, we developed a biohybrid hydrogel utilizing HEP as a major building block together with star-shaped PEG to form cell-instructive hydrogel matrices. [16] The high HEP concentration of the hydrogel allows the efficient administration of HEP-affine growth factors, such as FGF-2, [16] VEGF, [133] BMP-2, [134] SDF-1α, [135] GDNF, [136] NGF, [67] and TGF-β, [137] as well as the less-affine EGF. [138] Due to the high HEP concentration (i.e., the high number of protein-binding sites) in HEP-based hydrogels, multiple factors can be independently administered, as was shown for the parallel release of FGF-2 and VEGF [139] as well as FGF-2 and GDNF.…”
Section: Gag Hydrogels As Tunable Release Systemsmentioning
confidence: 99%
“…In another approach to improved dermal wound healing, the previously mentioned starPEG-HEP hydrogels were successfully utilized for the sustained release of TGF-β to induce myofibroblast differentiation. [137] …”
Section: Gag Hydrogels As Tunable Release Systemsmentioning
Glycosaminoglycans (GAGs) govern important functional characteristics of the extracellular matrix (ECM) in living tissues. Incorporation of GAGs into biomaterials opens up new routes for the presentation of signaling molecules, providing control over development, homeostasis, inflammation and tumor formation and progression. This review discusses recent approaches to GAG-based materials, highlighting the formation of modular, tunable biohybrid hydrogels by covalent and non-covalent conjugation schemes, including both theory-driven design concepts and advanced processing technologies. Examples of the application of the resulting materials in biomedical studies are provided. For perspective, we highlight solid-phase and chemoenzymatic oligosaccharide synthesis methods for GAG-derived motifs, rational and high-throughput design strategies for GAG-based materials and the utilization of the factor-scavenging characteristics of GAGs.
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