Rethinking osteocyte models in vitro: the need for mineralised extracellular matrix and network architecture.

Osteocytes inhabit one of the most extreme cellular microenvironments in the human body: a hydrated, hierarchically structured mineralised extracellular matrix where lacunar confinement, canalicular connectivity, fluid transport and mechanics are inseparable from cell function. In vitro osteocyte models have rapidly advanced through 3D culture, bioprinting, patterning, microfluidics, multicellular systems and controlled loading. Yet physiological interpretation often remains limited when marker expression, dendrite formation or bulk mineral deposition are assessed without defining the matrix and network architecture that deliver local cues. Here, we review engineered osteocyte microenvironment models through a matrix-centred and network architecture lens. We highlight advances in biomimetic mineralisation, viscoelastic and patterned hydrogels, dynamic microphysiological platforms and ECM-cell characterisation. We propose that progress will depend on modular, cross-correlative and computationally usable models that connect mineralised ECM, osteocyte network topology, transport and mechanics. Such models could move the field from descriptive osteocyte-like cultures toward interpretable niches that explain osteocyte behaviour.