In this sections, we explore the spider silk gland to illustrate how an organ tightly regulates material self-assembly 159 . Its physiology 160 , as the silkworm's 161 , have been extensively studied, making both excellent candidates for selfmicrofabrication. Spider silk is a prime example of a sustainable biological material with high mechanical performance and industrial applications 128 . Tougher than Kevlar 162 and not dependent on fossil fuels, spider silk has been extensively studied in various species 127 for its potential uses, notably in bulletproof vests or composites 128 . Replicating the silk's intricate microstructure synthetically has posed a challenge for decades, notably due to its complex processing conditions (Fig. ). Chemical microenvironments (ChemµEnv), such as the pH and salt concentrations, guide the self-assembly of biological materials through thermodynamics principles . Spider silk glands use specialized cell types to synthesize and secrete precursor proteins (spidroins) into the extracellular space. Other cells subsequently regulate the extracellular ChemµEnv 165 , driving the proper folding of proteins and material assembly . For these reasons, the spider silk gland example is detailed to showcase the role of multicellular tissues in hierarchical material production. However, an in-depth understanding of spider biology is not required in the following sections. In a spider, up to seven types of glands can produce silk with different properties, such as the tough dragline from the major ampullate (MA) glands or sticky fibers from the aggregate glands. Furthermore, environmental adaptations across 50,000 spider species have diversified their silk properties , including hydrophobic motifs in underwater spiders . We focus on Larinioides sclopetarius and Nephila golden orb weaver MA silk glands, due to the large literature available on these species, the high mechanical properties 127 and versatile applications of their silk 128 . Despite significant progress in spider silk research, no current technique can replicate the gland's complex material processing, encouraging efforts to develop spider silk gland organoids in the future. When trying to reproduce a biological material, approaches of various scales should be considered. At the organism scale, farming silkworm colonies industrially is efficient 169 but impractical for spiders, owing to their cannibalistic nature, as revealed by early attempts in the late 18 th century 170 . At the molecular scale, fully synthetic approaches can mimic specific aspects, such as spider silk discoveries improving nylon's properties 171 . Recombinant expression of silk protein (spidroin) has been developed in various hosts to better replicate the material composition . Many challenges associated with that approach have been addressed in the past decade 175 , including preventing aggregation in highly concentrated spidroin solutions . However, the yield and scalability continue to be significant bottlenecks 177 . Furthermore, the native silk dope composition is more complex than a few recombinant spidroins: including peptides, lipids, glycoproteins that serve functions such as lubrication, antibacterial and more 178 . While the synthesis function of silk glands can be simplified synthetically (e.g. recombinant silk solutions), the process of transforming the liquid phase into a solid fiber has not been fully replicated 179 . Wet spinning, dry spinning, and electrospinning 180 can produce tough threads but often induce aggregation instead of proper protein folding, reducing the resulting properties . Biomimetic aqueous spinning using microfluidics is the most promising synthetic approach yet that may control the ChemµEnv 181 . However, it does not match the in vivo multicellular regulation of the spinning process where MA glands regulate the pH, salts, water content and shear forces . To address the spinning challenge at a tissue scale, silkworm glands have been genetically engineered to secrete spidroin . Despite not fully mimicking the spider glands, transgenic silkworms present a promising strategy for largescale 184 , high-performance silk production 185 . It further highlights the importance of a multicellular organ for hierarchical material processing. These examples at various scales can be generalized to other biological materials and organs.