Disclosed herein are tissue-based drain manifolds comprising partially or completely decellularized tissue that has been processed to form tubes, columns, sheets, or other shapes and which are useful for managing the drainage of fluid and/or the administration of negative pressure at an implant site in a patient. The manifolds can be implanted in a patient and provide a natural scaffold in which native cells from surrounding tissue can migrate and proliferate, thereby avoiding the need to remove the implanted manifolds after drainage is complete.