Table 3.

Representative biomedical application scenarios, micro/nano-scale design requirements, and validation considerations for HM-based platforms synthesized from the present analysis and relevant literature

Application scenario	Biological/clinical challenge	Required micro/nano-scale properties	Representative nano-enabled design strategies	Characterization and translational bottlenecks
Wound healing	Infection, inflammation, impaired angiogenesis	Injectable, antibacterial, moisture-retaining, pro-angiogenic	Antibacterial agents, ROS-responsive release, composite hydrogels	Sterility, reproducibility, wound heterogeneity
OA/cartilage repair	Rapid joint clearance, inflammation, poor cartilage regeneration	Lubrication, retention, anti-inflammatory release, cartilage penetration	HA-based HMs, charge-guided HMs, self-lubricating microspheres	Long-term safety, joint residence, mechanical durability
Bone regeneration	Irregular defects, osteogenic induction, vascularization	Osteoinductivity, porosity, sustained growth-factor delivery	Growth-factor-loaded HMs, cell-laden HMs, composite scaffolds	Scale-up, mechanical matching, ectopic ossification risk
IDD	Avascular tissue, acidic/inflammatory microenvironment	Injectable, mechanically adaptive, anti-inflammatory, matrix-supportive	Cell/growth factor delivery, stimuli-responsive microspheres	Delivery accuracy, disc mechanics, long-term retention
Cell delivery/tissue engineering/granular biofabrication and 3D bioprinting	Cell survival, spatial organization, nutrient diffusion, printability, construct fidelity	Cell-compatible, interparticle porous, ECM-mimetic, tunable rheology, printable, degradable	Cell-laden microgels/HMs, granular hydrogel assembly, modular bioinks, microgel-based supporting matrices	Cell viability, rheology–mechanics balance, structural fidelity, reproducibility, GMP production
Cancer/embolization/immunotherapy and vaccine delivery	Local tumor control, embolic stability, immune activation, spatiotemporal cargo delivery	Local retention, embolic capability when required, imageability, controlled/staged release, immune compatibility	Drug-eluting or embolic HMs, immunomodulatory cargo-loaded HMs, microsphere vaccines, stimuli-responsive release	Off-target embolization, immune-related safety, biodistribution, release reproducibility, regulatory pathway
Organ-on-a-chip/disease modeling	Reconstructing tissue microenvironments	ECM-mimetic, tunable stiffness, modularity	Cell-laden microgels, multicompartmental HMs	Standardization, reproducibility, model validation
Controlled-release and long-acting delivery	Burst release, short exposure, unstable release profile	High loading, controlled diffusion, predictable degradation, formulation stability	PLGA/alginate/chitosan HMs, thermosensitive HMs, core–shell HMs	Release reproducibility, IVIVC, scale-up, storage stability
Bioimaging and biosensing	Signal stability, tissue penetration, biological background interference	Stable labeling, responsive interfaces, reproducible particle size, nanocomposite integration	Fluorescent/magnetic HMs, nanoparticle-integrated HMs, stimuli-responsive microgels	Sensitivity, specificity, calibration, long-term signal stability, in vivo tracking

Note: This table provides an interpretive synthesis based on the bibliometric, disease-landscape, and LDA topic-modeling results of the present study, supplemented by representative literature on established and emerging HM research fronts. It summarizes application-oriented platform requirements and translational considerations rather than providing a quantitative ranking of applications or evidence of established clinical efficacy

Abbreviations: ECM, extracellular matrix; GMP, Good Manufacturing Practice; HA, hyaluronic acid; HM, hydrogel microsphere; IDD, intervertebral disc degeneration; IVIVC, in vitro–in vivo correlation; OA, osteoarthritis; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic acid); ROS, reactive oxygen species