Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitmentopen access
- Authors
- Phan, V. H. Giang; Murugesan, Mohanapriya; Manivasagan, Panchanathan; Thanh Loc Nguyen; Thuy-Hien Phan; Cuong Hung Luu; Duy-Khiet Ho; Li, Yi; Kim, Jaeyun; Lee, Doo Sung; Thambi, Thavasyappan
- Issue Date
- Apr-2022
- Publisher
- MDPI
- Keywords
- thermo-responsive copolymers; sol-gel phase transition; injectable hydrogels; protein-polymer conjugation; immune cell recruitment; dendritic cells
- Citation
- PHARMACEUTICS, v.14, no.4
- Journal Title
- PHARMACEUTICS
- Volume
- 14
- Number
- 4
- URI
- https://scholarworks.bwise.kr/kumoh/handle/2020.sw.kumoh/28236
- DOI
- 10.3390/pharmaceutics14040709
- ISSN
- 1999-4923
1999-4923
- Abstract
- Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(epsilon-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 mu g/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs.
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