Autologous Extracellular Matrix‐Based Cell‐Free Therapy for Tissue Regeneration Through Trem2 ⁺ Macrophages Mediated Angiogenesis

ABSTRACT The extracellular matrix (ECM) is vital for tissue regeneration and remodeling by providing structural support and regulating cell behavior. Bioactive membranes derived from decellularized ECM show promising regenerative potential in many fields. However, they still face challenges such as immune rejection, structural disparities, and high costs associated with human‐derived materials. These issues hinder their widespread clinical application and limit their adaptability to personalized treatments. Further research is needed to improve the safety, efficacy, and accessibility of ECM‐based materials. This study develops an autologous ECM‐based membrane, termed adipose‐derived matrix film (ADF), using a simple physical method inspired by traditional “ papermaking .” ADF exhibits favorable biological activity and mechanical strength, essential for tissue regeneration. Its production is efficient, facilitating clinical translation. Additionally, ADF can be stored long‐term at low temperatures, enabling the establishment of an “ ECM bank ” for personalized medicine. As a cell‐free therapy, ADF enhances soft tissue regeneration and wound healing, with Trem2 + macrophages playing a key role in neovascularization. We introduce a novel autologous adipose ECM‐derived bio‐membrane, offering new perspectives on ECM preservation and Trem2 + macrophage‐mediated regeneration. These findings significantly advance cell‐free regenerative medicine and redefine fundamental mechanisms of tissue repair and vascular restoration.