The manipulation of cell surfaces in anchorage-dependent cells can help overcome difficulties presented during cell handling and application. Silica-based protective mechanisms existing in free-floating microorganisms may be used as inspiration for sustaining human cell survival in suspension. Gathering on this, herein human adipose-derived mesenchymal stem cells (hASCs) are partially coated with a hard silica layer that operates as a supporting platform for individual cells in suspension. Inspired by the organic templates involved in biosilicification, a novel chitosan (CHT) derivative displaying fully natural quaternary amine moieties is synthetized via a rapid, one-pot strategy. Silicification is promoted on individual hASCs surfaces via a two-step process: a priming step onto previously adhered cell with this CHT derivative, followed by a biocompatible sol-gel process. hASCs holding a silica backpack exhibit enhanced cell survival in suspension conditions and can spread and acquire a more adherent phenotype. This new protocol for cell-surface modification also provides a new generation of hybrid materials with functionalization of the silica backpack, which can be applied to different areas such as tissue engineering, biosensing, drug delivery, and targeted cell-based therapies.