Regenerating Hair in Prevascularized Tissue Space Formed by a Controllable Foreign Body Reaction

Abstract Intracutaneous transplantation of trichogenic cells is a currently endorsed strategy to realize hair regeneration in vivo. However, skin is not the most advantageous transplant site due to the robust mechanical property and deficient physiological perfusion. Herein, a subcutaneous space made of prevascularized collagen fibers (PVCF) generated by controlling the duration of in situ foreign body reaction is reported. In contrast to skin, an optimally preprogrammed PVCF presents a larger tissue volume (171 mm 3 ), low Young's modulus (1/2‐fold), high flexibility high mechanical energy dissipation rate (1.3‐fold), highly permeable surface structure, and plentiful vascular network. Remarkably, cells transplanted into PVCF suffer less apoptosis and necrosis, and generate more mature hairs (≈289 per site) than that in intracutaneous transplantation (≈177 per site). The RNA‐sequencing profiling indicates similar trends under molecular level. This work provides a promising strategy to improve graft site microenvironment physiologically and mechanically, with a low‐cost and simple fabrication process.