Integrating resource utilization and bioregenerative life support systems for sustainable space exploration

The long-term presence of humans in space depends on reducing reliance on Earth's resupply of materials and resources. In situ resource utilization (ISRU) represents a sustainable approach to support human activities in space by converting local materials into consumables, propellants, and structural feedstocks. In parallel, bioregenerative life support systems (BLSS) primarily sustain internal loop closure (LC) by regenerating air, H₂O, nutrients, and food from habitat-contained streams. Traditional ISRU concepts have primarily focused on abiotic technologies that process rocks, regolith, and atmospheric components to extract O₂, H₂O, and metals, although biotic approaches are also under investigation. Biological and bio-hybrid approaches, guided by microorganisms and other living systems, could complement these technologies by supporting both external resource conversion and internal LC in future space exploration. In this review, we adopt a resource-centric framework to compare abiotic, biotic, and coupled resources acquisition pathways across the main functional domains relevant to both ISRU and BLSS, treated as operationally distinct but architecturally coupled subsystems within a broader resource-management framework. We discuss the main functional domains required for human settlement, spanning external resource conversion (O₂, CO₂, H₂, CH₄, H₂O, materials, manufacturing, energy) and internal regenerative functions (food production, air and H₂O revitalization, and waste recycling). For each domain, we describe representative abiotic (e.g., MOXIE, ROXY, molten-regolith electrolysis, fission surface power, and advanced solar arrays) and biotic systems, for both ISRU-relevant bioprocesses (e.g., biomining, biopolymer production) and BLSS components (e.g., plant-growth and microbial recycling loops). The most realistic path toward sustainable human settlements beyond Earth orbit lies in coupled ISRU-BLSS architectures in which external resource acquisition and internal regenerative loops are coordinated across shared material and energy flows.