Immunized Microspheres Engineered Hydrogel Membrane for Reprogramming Macrophage and Mucosal Repair

Abstract

The “double‐edged sword” effect of macrophages under the influence of different microenvironments determines the outcome and prognosis of tissue injury. Accurate and stable reprogramming macrophages (Mφ) are the key to rapid wound healing. In this study, an immunized microsphere‐engineered GelMA hydrogel membrane is constructed for oral mucosa treatment. The nanoporous poly(lactide‐co‐glycolide) (PLGA) microsphere drug delivery system combined with the photo‐cross‐linkable hydrogel is used to release the soybean lecithin (SL)and IL‐4 complexes (SL/IL‐4) sustainedly. In this way, it is realized effective wound fit, improvement of drug encapsulation, and stable triphasic release of interleukin‐4 (IL‐4). In both in vivo and in vitro experiments, it is demonstrated that the hydrogel membrane can reprogram macrophages in the microenvironment into M2Mφ anti‐inflammatory types, thereby inhibiting the local excessive inflammatory response. Meanwhile, high levels of platelet‐derived growth factor (PDGF) secreted by M2Mφ macrophages enhanced neovascular maturation by 5.7‐fold, which assisted in achieving rapid healing of oral mucosa. These findings suggest that the immuno‐engineered hydrogel membrane system can re‐modulating the biological effects of Mφ, and potentiating the maturation of neovascularization, ultimately achieving the rapid repair of mucosal tissue. This new strategy is expected to be a safe and promising immunomodulatory biomimetic material for clinical translation.

Injectable Temperature-Sensitive Hydrogel Loaded with IL-36Ra for the Relief of Osteoarthritis

“…It is reported that the accumulation of metabolites of PLGA may still induce inflammation and aggravate OA . However, some studies over the years did not report the evident inflammation induced by PLGA, and due to the unique advantages of this hydrogel delivery system, we believe that its possible local pro-inflammatory effects are weak and acceptable, and it was confirmed in our animal studies. ,− IL-36Ra could be easily and uniformly dispersed in polymer aqueous solution by mixing at low or room temperature. The loading of IL-36Ra did not affect the injectability and temperature-induced gelation of the polymer/water system.…”

Recent advances in GelMA hydrogel transplantation for musculoskeletal disorders and related disease treatment

“…This anti-inflammatory platform not only exerts excellent anti-inflammatory effects, but is also biocompatible and shows good ability to promote cartilage regeneration in vitro . In order to modulate the immunological properties of macrophages, Wen et al 30 combined a nanoporous poly (propylene-co-ethylene-glycolide) (PLGA) microsphere delivery system with GelMA hydrogels to continuously release soy lecithin (SL) and IL-4 complexes (SL/IL-4), an approach that inhibits excessive local inflammatory counter-reactions while promoting vascular maturation and ultimately rapid tissue repair. Optimising the immunomodulatory capacity of GelMA in vivo is an important component of regenerative medicine and could provide new ideas for future clinical practice.…”

“…Amongst all immune cells, macrophages are one of the most important cells in the process of inducing an immune response to biomaterials. Excellent biomaterials based on GelMA hydrogels, when injected into the body, should have good immunomodulatory properties, including promoting the M2 polarisation of macrophages, inhibiting M1 polarisation, regulating the production of T cells and reducing the inflammatory response, thereby promoting the regeneration of blood vessels, bone, cartilage, nerves, skin and other tissues [28][29][30][31][32]. For instance, Li et al [33] constructed an injectable photocrosslinkable porous GelMA/serine protein glycidyl methacrylate (SilMA) hydrogel encapsulating gingival tissue-derived MSCs (GMSCs) that promoted M2 polarization while inhibiting M1 polarization in vitro.…”

Releasable, Immune‐Instructive, Bioinspired Multilayer Coating Resists Implant‐Induced Fibrosis while Accelerating Tissue Repair

“…Given the causal role of activated macrophages in FBRs and many diseases involving inflammation and fibrosis, [51][52][53][54] it is reasonable to assume that the abnormal polarization of resident naïve macrophages, which exist in major tissues throughout the body, is a potential risk factor. Although M2-inducible cytokines (e.g., IL-4) delivered from biomaterials have been shown to improve tissue repair, [55,56] these cytokines strongly stimulate naïve M0 macrophages to increase the production of cytokines and specific surface molecules in response to a given stimuli, leading to potential adverse effects (as discussed later). [7,38,39] In this regard, PSLs offer a significant advantage that they specifically react with M1 macrophages, not M0 macrophages, to polarize M1 into M2-like phenotypes.…”