Search Results
Chemokine‐Capturing Wound Contact Layer Rescues Dermal Healing
2021, Schirmer, Lucas, Atallah, Passant, Freudenberg, Uwe, Werner, Carsten
Excessive inflammation often impedes the healing of chronic wounds. Scavenging of chemokines by multiarmed poly(ethylene glycol)-glycosaminoglycan (starPEG-GAG) hydrogels has recently been shown to support regeneration in a diabetic mouse chronic skin wound model. Herein, a textile-starPEG-GAG composite wound contact layer (WCL) capable of selectively sequestering pro-inflammatory chemokines is reported. Systematic variation of the local and integral charge densities of the starPEG-GAG hydrogel component allows for tailoring its affinity profile for biomolecular signals of the wound milieu. The composite WCL is subsequently tested in a large animal (porcine) model of human wound healing disorders. Dampening excessive inflammatory signals without affecting the levels of pro-regenerative growth factors, the starPEG-GAG hydrogel-based WCL treatment induced healing with increased granulation tissue formation, angiogenesis, and deposition of connective tissue (collagen fibers). Thus, this biomaterials technology expands the scope of a new anti-inflammatory therapy toward clinical use.
Amphiphilic Copolymers for Versatile, Facile, and In Situ Tunable Surface Biofunctionalization
2021, Ruland, André, Schenker, Saskia, Schirmer, Lucas, Friedrichs, Jens, Meinhardt, Andrea, Schwartz, Véronique B., Kaiser, Nadine, Konradi, Rupert, MacDonald, William, Helmecke, Tina, Sikosana, Melissa K.L.N., Valtin, Juliane, Hahn, Dominik, Renner, Lars D., Werner, Carsten, Freudenberg, Uwe
Precision surface engineering is key to advanced biomaterials. A new platform of PEGylated styrene-maleic acid copolymers for adsorptive surface biofunctionalization is reported. Balanced amphiphilicity renders the copolymers water-soluble but strongly affine for surfaces. Fine-tuning of their molecular architecture provides control over adsorptive anchorage onto specific materials-which is why they are referred to as "anchor polymers" (APs)-and over structural characteristics of the adsorbed layers. Conjugatable with an array of bioactives-including cytokine-complexing glycosaminoglycans, cell-adhesion-mediating peptides and antimicrobials-APs can be applied to customize materials for demanding biotechnologies in uniquely versatile, simple, and robust ways. Moreover, homo- and heterodisplacement of adsorbed APs provide unprecedented means of in situ alteration and renewal of the functionalized surfaces. The related options are exemplified with proof-of-concept experiments of controlled bacterial adhesion, human umbilical vein endothelial cell, and induced pluripotent cell growth on AP-functionalized surfaces.
Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain
2020, Schirmer, Lucas, Hoornaert, Chloé, Le Blon, Debbie, Eigel, Dimitri, Neto, Catia, Gumbleton, Mark, Welzel, Petra B., Rosser, Anne E., Werner, Carsten, Ponsaerts, Peter, Newland, Ben
Interleukin-13 (IL-13) drives cells of myeloid origin towards a more anti-inflammatory phenotype, but delivery to the brain remains problematic. Herein, we show that heparin-based cryogel microcarriers load high amounts of IL-13, releasing it slowly. Intra-striatal injection of loaded microcarriers caused local up-regulation of ARG1 in myeloid cells for pro-regenerative immunomodulation in the brain. © 2020 The Royal Society of Chemistry.