Injectable Supramolecular Hydrogel/Microgel Composites for Therapeutic Delivery

• Published in: Macromolecular bioscience Vol. 19; no. 1; pp. e1800248 - n/a
• Main Authors: Chen, Minna H., Chung, Jennifer J., Mealy, Joshua E., Zaman, Samir, Li, Elizabeth C., Arisi, Maria F., Atluri, Pavan, Burdick, Jason A.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.01.2019
• Subjects: Animals; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacokinetics; Biocompatible Materials - pharmacology; Biomaterials; Biomedical materials; Cardiac output; Composite materials; composites; Controlled release; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Disease Models, Animal; drug delivery; Encapsulation; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Injectability; Injection; Interleukin-10 - chemistry; Interleukin-10 - pharmacokinetics; Interleukin-10 - pharmacology; Interleukins; Macrophages; Microfluidics; Microgels; Myocardial infarction; Myocardial Infarction - metabolism; Rats; Rheological properties; supramolecular; Three dimensional printing; Tissue engineering; composites; supramolecular; hydrogels; drug delivery; microgels
• ISSN: 1616-5187; 1616-5195; 1616-5195
• DOI: 10.1002/mabi.201800248

Shear‐thinning hydrogels are useful for biomedical applications, from 3D bioprinting to injectable biomaterials. Although they have the appropriate properties for injection, it may be advantageous to decouple injectability from the controlled release of encapsulated therapeutics. Toward this, composites of hydrogels and encapsulated microgels are introduced with microgels that are fabricated via microfluidics. The microgel cross‐linker controls degradation and entrapped molecule release, and the concentration of microgels alters composite hydrogel rheological properties. For the treatment of myocardial infarction (MI), interleukin‐10 (IL‐10) is encapsulated in microgels and released from composites. In a rat model of MI, composites with IL‐10 reduce macrophage density after 1 week and improve scar thickness, ejection fraction, cardiac output, and the size of vascular structures after 4 weeks when compared to saline injection. Improvements are also observed with the composite without IL‐10 over saline, emphasizing the role of injectable hydrogels alone on tissue repair. Guest–host hyaluronic acid hydrogels are combined with covalently cross‐linked hyaluronic acid microgels with encapsulated therapeutics to create composites that are injectable and can deliver therapeutics with controlled release kinetics. Here, feasibility is demonstrated using composite hydrogels to deliver interleukin‐10 in a rat MI model.