Celastrol-Loaded Hydrogels for Tissue Engineering

The objective of this study was to explore the emerging role of celastrol-loaded hydrogels as advanced biomaterial platforms for tissue engineering and regenerative medicine. Traditional Chinese medicine active ingredients face limitations from rapid clearance and low bioavailability. This study examines how integrating the pentacyclic triterpene quinone methide, celastrol, into controlled-release natural and synthetic hydrogels overcomes these challenges to modulate the local injury microenvironment. A structured literature search was conducted across multiple databases, including PubMed, Scopus, Web of Science, and CNKI, covering publications from January 2000 to March 2026. Data including hydrogel networks, spatial–temporal release kinetics, and therapeutic outcomes were extracted and synthesized across 15 selected preclinical studies. The findings indicate that celastrol exhibits a narrow therapeutic window and severe multi-organ toxicity. However, localization within hydrogels shields host organs from apoptotic injury while ensuring zero-order diffusion or stimuli-responsive release. Mechanistically, these systems accelerate anatomical repair by shifting tissue microenvironments from chronic inflammation and fibrosis to a pro-healing state. This therapeutic transition is driven by a multi-target cascade involving NF-κB pathway suppression, Nrf2/HO-1 antioxidant activation, HSP70 cytoprotection, M2 macrophage polarization, and pro-fibrotic TGF-β/Smad signaling inhibition. Biomimetic natural polymer backbones further eliminate carrier-induced stress, providing structural cues to support cell transplantation, stem-cell attachment, and endogenous extracellular matrix remodeling. Celastrol-loaded hydrogels extend therapeutic effects on functional tissue regeneration rather than mechanical scarring. Clinical translation depends on the safety assessments for degradation tuning, matrix reliability, and long-term in vivo pharmacokinetics.