The extracellular matrix (ECM) directs all phases of healing following trauma or disease and is therefore a natural source of prosthetic mesh material that can be used strategically to induce the repair and restoration of soft tissues following surgery. Biomaterials such as Surgisis (Cook Biotech Incorporated, West Lafayette, IN, USA), which are derived from natural ECM, provide the extracellular components necessary to direct the healing response, allow for the proliferation of new, healthy tissue and restore tissue integrity to the damaged site. The 3-D organization of these extracellular components distinguishes the Surgisis mesh from synthetic materials and is associated with constructive tissue remodelling instead of scar tissue. Common features of this ECM-assisted tissue remodelling include angiogenesis, recruitment of circulating progenitor cells and constructive remodelling of damaged tissue structures. The tissue response to this biologic mesh is discussed in the context of recent reports on clinical hernia repair.