Immune-instructive biofabrication for musculoskeletal tissue regeneration

Musculoskeletal repair requires coordinated tissue organization and host responses that evolve across space and time. Immune-instructive biofabrication aims to use material and manufacturing design to create reproducible biological exposures that influence host function and support regeneration. This narrative review clarifies the distinction between immune association, modulation, regulation, and instruction, and considers how biofabrication choices may shape immune-regenerative interactions across musculoskeletal tissues. Current evidence is organized around the location, timing, agent, and functional dose of manufactured cues, together with the multicellular networks involved in healing. Although engineered constructs can influence inflammatory responses while supporting tissue repair, direct evidence linking specific manufacturing features to causal immune mechanisms and durable function remains limited. Progress will require appropriately matched controls, spatial and longitudinal assessment, mechanistic testing, tissue-relevant functional outcomes, and standardized potency measures. This framework provides a basis for designing and evaluating musculoskeletal biofabrication strategies that integrate structural reconstruction with controlled host-response modulation.