Photocrosslinkable hydrogel of ibuprofen-chitosan methacrylate modulates inflammatory response.

Methacrylated biopolymers are unique and attractive in preparing photocrosslinkable hydrogels in biomedical applications. Here we report a novel chitosan (CS) derivative-based injectable hydrogel with anti-inflammatory capacity via methacrylation modification. First, ibuprofen (IBU) was conjugated to the backbone of CS by carbodiimide chemistry to obtain IBU-CS conjugate, which converts water-insoluble unmodified CS into water-soluble IBU-CS conjugate. The IBU-CS conjugate did not precipitate at the pH of 7, which was beneficial to subsequent chemical modification with methacrylic anhydride to prepare IBU-CS methacrylate (IBU-CS-MA) with significantly higher methacrylation substitution. Photocrosslinkable in situ gel formation of injectable IBU-CS-MA hydrogel was verified using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) initiator under visible light. The IBU-CS-MA hydrogel showed good cytocompatibility as revealed by encapsulating and in vitro culturing murine fibroblasts within hydrogels. It promoted macrophage polarization toward M2 phenotype, as well as downregulated pro-inflammatory gene expression and upregulated anti-inflammatory gene expression of macrophages. The hydrogel also significantly reduced the reactive oxygen specifies (ROS) and nitrogen oxide (NO) produced by lipopolysaccharides (LPS)-stimulated macrophages. Upon subcutaneous implantation in a rat model, it significantly mitigated inflammatory responses as shown by significantly lower inflammatory cell density, less cell infiltration, and much thinner fibrous capsule compared with CS methacrylate (CS-MA) hydrogel. This study suggests that IBU-CS conjugate represents a feasible strategy for preparing CS-based methacrylate hydrogels for biomedical applications.

Injectable Hydrogel of Chitosan-Octyl Itaconate Conjugate Modulates Inflammatory Response.

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (ß-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.