(1) Abstract
This study develops a 3D-printed biochemical-mechano-thermal responsive multicellular oral tumor organoid platform, combining a photothermal elastic scaffold with decellularized oral mucosa ECM hydrogel. Bioorthogonal anchoring spatially partitions cancer cells and macrophages, while cyclic mechanical stretch and near-infrared photothermal stimulation are applied to dissect effects on tumor proliferation, metabolism, immune polarization, and chemoresistance.

(2) Background
The oral tumor microenvironment includes matrix biochemical cues, cancer-immune interactions, mechanical deformation, and thermal fluctuations. Conventional static organoid models poorly reproduce dynamic physical stimulation and spatial immune architecture, limiting mechanistic studies of drug resistance.

(3) Main Content
The platform integrates a 3D-printed elastic scaffold, photothermal coating, bioorthogonal cell anchorage, and ECM hydrogel, forming a scaffold-anchored cancer compartment and a hydrogel-encapsulated macrophage compartment. Under dynamic stimulation, cancer phenotype, macrophage polarization, transcriptomics, glycolysis, stemness, and doxorubicin resistance are evaluated, together with an in vivo xenograft model.

(4) Study Design
Material physicochemical and photothermal characterization, cytocompatibility and anchorage stability assays are performed. Oral cancer cells and macrophages are cultured alone or in coculture under cyclic mechanical and near-infrared photothermal stimulation. RNA sequencing, metabolic analysis, immunofluorescence, flow cytometry, protein assays, and xenograft models are combined.

(5) Results
Dynamic biochemical-mechano-thermal stimulation promotes cancer cell proliferation and glycolytic reprogramming, induces M2-like macrophage polarization, enhances stress adaptation, EMT-like changes, stemness programs, and chemoresistance. In vivo dynamic conditioning accelerates tumor growth, angiogenesis, and resistance-associated molecular programs.

(6) Future Directions
Future work should standardize mechanical and thermal parameters, separate their individual contributions, and combine orthotopic models, patient-derived organoids, and long-term culture with multi-omics to dissect physical stimulation-immune-metabolic coupling and resistance networks.

We provide full-process services for various material designs (including highly innovative scheme design, preparation, characterization, in vitro and in vivo validation (cell/animal experiments), etc.): a postdoctoral team (with multiple high-impact publications in Zone 1 journals) can meet all kinds of tricky and challenging requirements, including hydrogels / drug delivery / nanomaterials / polymers / liposomes / microneedle drug delivery, etc. We can assist with project design / NSFC grant applications / publication of high-impact Zone 1 and Zone 2 papers in journals such as AFM, SCI, AM, etc. Welcome to consult 👇️
17768014569 (Senior Engineer Gao)
17761925168 (Engineer Zhang)
18013729810 (Engineer Yang)