Novel Balanced Charged Alginate/PEI Polyelectrolyte Hydrogel that Resists Foreign-Body Reaction

Abstract

Foreign-body reaction (FBR) has been a long-term obstacle for implantable biomedical devices and materials, especially to those that require mass/signal transport between the implants and the body. However, currently, very limited biomaterials can mitigate FBR. In this work, we develop a balanced charged polyelectrolyte hydrogel that can efficiently resist FBR and collagenous capsule formation in a mouse model. Using this new strategy, we can easily tune the antifouling properties of the polyelectrolyte hydrogels by changing the ratio of negatively charged alginate and positively charged poly(ethylene imine). We find that at the optimum ratio where the net charge of hydrogel is neutral, the adhesion of proteins, cells, bacteria, and fresh blood on its surface can be significantly inhibited, indicating its excellent antifouling properties. In vivo studies show that after being implanted subcutaneously, this balanced charged hydrogel can prevent the capsule formation for at least 3 months. Furthermore, immunofluorescent staining results indicate that this balanced charged hydrogel elicits negligible inflammation, significantly reducing macrophage migration to the tissue-implant interface. This flexible and versatile approach holds a great promise for designing a wide spread of new antifouling hydrogels and using as immunoisolation materials for biomedical applications.

Ultrafast self-gelling powder mediates robust wet adhesion to promote healing of gastrointestinal perforations

“…The toxicity of freely diffusing PEI is mainly associated with its strong positive charge, which leads to strong interaction of PEI with cell membranes, resulting in cell death and apoptosis (59). To reduce the toxicity of PEI, different chemical modifications of PEI have been explored (60)(61)(62). For example, Zhang et al (62) prepared an alginate/PEI polyelectrolyte hydrogel with balanced charge, which not only showed excellent in vitro cytocompatibility and hemocompatibility but also showed minimal foreign body reaction in a mouse model.…”

“…To reduce the toxicity of PEI, different chemical modifications of PEI have been explored (60)(61)(62). For example, Zhang et al (62) prepared an alginate/PEI polyelectrolyte hydrogel with balanced charge, which not only showed excellent in vitro cytocompatibility and hemocompatibility but also showed minimal foreign body reaction in a mouse model. In our work, at the selected weight ratio of PEI and PAA (5:5), the charge balance between PEI and PAA could be achieved, resulting in optimal zeta potential (−0.1 ± 1.1 mV) and pH of the mixture (7.0 ± 0.04) (fig.…”

Dealing with the Foreign‐Body Response to Implanted Biomaterials: Strategies and Applications of New Materials

“…The balanced alginate/PEI hydrogels showed favorable antifouling properties and could prevent inflammation and capsule formation for at least 3 months after subcutaneous implantation. [ 275 ] With the continuous development of antifouling and anti‐FBR zwitterionic polymers, zwitterionic materials are promising for their application in biomedical related fields to improve the quality of human life.…”

Silk‐Inspired β‐Peptide Materials Resist Fouling and the Foreign‐Body Response

“…Therefore, the long‐term in vivo application of PEG is limited in biomedical applications. Other materials, such as polyglycidols, poly(2‐oxazoline)s, polyzwitterions, peptides, and peptoids, have been reported to resist non‐specific protein adsorption, yet few materials demonstrate promising anti‐FBR properties and the development of materials with anti‐FBR properties that are suitable for implanted biomaterial applications remains a formidable challenge …”