Poloxamers, a class of non-ionic triblock copolymers composed of polyethylene oxide (PEO) and polypropylene oxide (PPO) segments, have gained significant attention in regenerative medicine due to their unique thermosensitive gelation properties. Among them, poloxamer 127 (F-127) is widely used in biomedical applications owing to its biocompatibility, low toxicity, and FDA approval. These polymers exhibit a reversible sol-gel transition at physiological temperatures, enabling minimally invasive delivery via injection followed by in situ solidification into a stable hydrogel matrix. This property makes poloxamer-based systems ideal for intrauterine therapeutic delivery in the treatment of endometrial injury and intrauterine adhesions (IUA).
One of the most promising applications of poloxamer hydrogels is the localized and sustained release of estrogen, particularly 17β-estradiol (E2), which plays a critical role in endometrial proliferation and anti-fibrotic activity.84449-90-1 supplier Our group developed an E2-loaded thermosensitive poloxamer 127 (E2-HP) hydrogel that transforms from a liquid solution at room temperature to a semi-solid gel at 37°C, ensuring prolonged residence time within the uterine cavity—up to 48 hours—compared to rapid systemic clearance of free E2 within two hours. The sustained release profile over 72 hours enables continuous stimulation of vascularization and suppression of fibrosis, thereby promoting tissue remodeling and functional recovery.
In a rat model of IUA, E2-HP hydrogel significantly reduced fibrotic areas and enhanced endometrial thickness, with concomitant upregulation of key factors such as kisspeptin, activated through ERK1/2 and MAPK pathways. Moreover, the hydrogel mitigated endoplasmic reticulum (ER) stress-induced apoptosis, a known contributor to impaired regeneration after injury. These findings highlight the dual benefit of hormone delivery: not only stimulating repair but also protecting cells from stress-related damage.95233-18-4 InChIKey
Further advancements include the development of a nano-composite aloe/poloxamer hydrogel loaded with E2 encapsulated in nanoparticulate-decellularized uterine extracellular matrix (uECMNPs). This system combines the advantages of natural ECM components with the tunable delivery properties of poloxamers. The uECMNPs improved E2 solubility and enabled extended release, while the poloxamer matrix provided structural stability and bioadhesion. In vivo studies demonstrated that this multi-functional platform enhanced endometrial cell proliferation, reduced apoptosis, and downregulated pro-fibrotic markers such as TGF-β1 and TNF-α. Histological analysis revealed markedly decreased collagen deposition and increased glandular formation, indicating effective prevention of re-adhesion.
Beyond hormones, poloxamer hydrogels have been successfully employed to deliver growth factors such as keratinocyte growth factor (KGF). By modifying the polymer with heparin, researchers achieved high-affinity binding and prolonged release of KGF over seven days without loss of biological activity. Subsequent studies incorporated -polylysine (PLL) to enhance bioadhesivity, increasing adhesive force tenfold compared to unmodified gels. The resulting KGF-EPL-HP hydrogel promoted endothelial migration, increased CD31 expression, and facilitated epithelial repair by restoring the local microenvironment and reducing inflammation.PMID:30969675
These hydrogels also support cell delivery. For instance, bone marrow mesenchymal stem cells (BMSCs) were encapsulated in a thermoresponsive PF-127/vitamin C hydrogel, where vitamin C acted as both a stabilizer and antioxidant, suppressing TNF-α and IL-6 secretion while boosting IL-10 levels. This formulation improved redox balance and enhanced cell survival, leading to significant restoration of endometrial thickness and reduction in fibrosis.
In conclusion, poloxamer-based thermosensitive hydrogels represent a highly adaptable and clinically relevant strategy for endometrial regeneration. Their ability to undergo in situ gelation, combined with tunable drug release profiles and enhanced bioadhesion, positions them as superior platforms for delivering hormones, growth factors, and stem cells. Future innovations will focus on integrating multiple therapeutics into single systems, leveraging stimuli-responsive behaviors, and advancing clinical trials to validate long-term safety and efficacy in treating recurrent IUA.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com