Purpose: To evaluate the effects of methodological variation of biophysical therapies on wound healing outcomes, as a preliminary study to develop a composite wound healing device. Methods: A literature search was focused on the variable devices, sys-tem configurations, input parameters, and treatment durations of negative pressure wound therapy (NPWT), electrical stimulation (ES), and low-level light therapy (LLLT) from 2011 to July 2016. Results: In NPWT, lower vacuum pressures of ?50 and ?80 mmHg achieved similar tissue perfusion outcomes as earlier recommendations of ?125 mmHg, while there is no established regimen with respect to continuous, square wave, or triangular NP waveform due to inconsistent results. Use of wound filler may contribute to improved tissue granulation when compared to topical NP. An ES configuration of high-voltage pulsed current with the stimulation electrode placed in the wound bed best resembles the endogenous skin current, which guides cellular migration. However, no studies have established optimal stimulation parameters. For LLLT, laser and LED proved similarly effective. Although red light has been almost exclusively used in human pressure ulcer treatment, studies comparing blue, green, and red wavelengths more consistently show biological effects using green light. Conclu-sions: Variation in the application of mechanical, electrical, and radiant energies may be used to modulate wound healing pathways. To 2012, no studies have examined use of these biophysical modalities in combination. Further methodological studies with a systems approach would help define optimal treatment protocols for improved wound healing outcomes in clinical practice.