Development and characterization of an immunomodulatory and injectable system composed of collagen modified with trifunctional oligourethanes and silica

• Published in: Biomaterials science 2019-11, Vol.7 (11), p.4547-4557
• Main Authors: Muñoz-González, Pedro U, Rooney, Peadar, Mohd Isa, Isma Liza, Pandit, Abhay, Delgado, Jorge, Flores-Moreno, Mauricio, Castellano, Laura E, Mendoza-Novelo, Birzabith
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biomedical materials; Collagen; Collagen - chemistry; Collagen - pharmacology; Crosslinking; Cytokines; Drug Delivery Systems; Entrapment; Gels; Gels - chemistry; Immune system; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Inflammation - drug therapy; Inflammation - pathology; Inflammatory response; Intervertebral discs; Macrophages; Macrophages - drug effects; Mice; RAW 264.7 Cells; Rheological properties; Self-assembly; Silicon dioxide; Silicon Dioxide - chemistry; Storage modulus; Urethane - chemistry; Wound healing; Wound Healing - drug effects
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/c9bm00702d

Immunomodulatory biomaterials have emerged as a promising approach to engineer wound healing. To achieve this task, the bioactivity of the biomaterials and an easy application are two key desirable characteristics. This work reports an injectable gel system containing immune cells primed for wound healing. By combining the self-assembly of type I collagen, cross-linked with trifunctional oligourethanes, and silica particle entrapment, the structured collagen network acts as a delivery vehicle for macrophages. This structured collagen network primes the macrophages for an anti-inflammatory response. Rheological measurements suggest that the mixture of liquid precursors can be safely stored at low temperatures and low pH (4 °C, pH 3) for at least one month. After pH neutralization and injection, gels with a storage modulus of 50-80 Pa are obtained in five minutes. Several immunocytochemistry and ELISA tests strongly suggest that mouse and human macrophages are stimulated by the material to up-regulate the production of anti-inflammatory cytokines, while down-regulating the production of pro-inflammatory cytokines. The injection of gel in an ex vivo inflammation model of intervertebral discs demonstrated that it is possible to transit from a pro-inflammatory to an anti-inflammatory microenvironment. Altogether, the results suggest that this gel can polarize the macrophage response and promote a surrounding anti-inflammatory microenvironment ready for injection for wound healing applications. Injectable gel based on collagen, oligourethanes and silica acts as a delivery vehicle for macrophages primed for an anti-inflammatory response.