The present invention is based on the discovery that a true tissue morphogen such as OP-1 provided systemically, alone in its mature dimeric form, or as part of a soluble complex, can induce new replacement tissue regeneration at a localized, permissive defect site distal to the site of administration. Specifically, systemically administered protein is sufficient to induce formation of new functional replacement tissue, sufficient to repair a local defect in a tissue, including skeletal or orthopedic tissues, liver, pancreas, lung, cardiac, renal, uterine, intestinal, gastrointestinal tissue. (As used herein, "orthopedic" or "skeletal" or "joint" or "chondrogenic" tissue is understood to encompass the skeletal and skeletal joint tissues: bone, cartilage, tendon, ligament, and synovial membrane tissues.) It further has been discovered that a single injection of morphogenic protein is sufficient to induce the desired biological effect, and that administration is not time-sensitive, provided mesenchymal progenitor cells are accessible to the defect site. That is, morphogenic protein can be provided to an individual having a local permissive defect site, shortly after creation of the defect, or at some significant time later, including, without limitation, after the initiation of fibrotic tissue formation. Thus, means now are available for enhancing restoration of tissue function and/or repair or regeneration of functional replacement tissue by systemically administering morphogenic protein, at times significantly after creation of the defect. The methods and formulations can be used to repair local defects without requiring surgical intervention; can enhance the rate and quality of new replacement tissue formation, particularly in compromised individuals with a reduced capacity to undergo spontaneous healing, and can be used to induce new tissue formation even after the initiation of fibrosis at the defect site. This discovery is disclosed in copending U.S. Patent Application filed on even date herewith, the disclosure of which is incorporated herein by reference.