AbstractMinimally invasive reconstruction combines principles of tissue engineering and regenerative medicine for healing complex wounds. This approach was successfully demonstrated on a 64-year-old diabetic and hypertensive male patient, who was brought unconscious to our emergency after surviving an automobile collision with severe brain and right-dominant upper extremity injuries. Uncontrolled hyperglycemia, severe anemia, diffuse axonal brain injury, wrist drop, and loss of thumb extension and abduction were noted. Extensive degloving, skin necrosis, extensor and flexor forearm muscle crush injuries, and ruptured extensor tendons were observed. Serial wound debridement combined with platelet-poor plasma injection into the muscles, platelet-rich plasma injections into the tendons and subcutis, and low-negative pressure wound therapy were performed sequentially to salvage the injured soft-tissues. Improvements were noticed during the second exploration after 5 days. Surviving muscles showed adequate vascularization and revival of innervation during the third exploration after another 5 days. Thereafter, absorbable synthetic tissue scaffold was applied over a sizeable 270 cm2 wound as a flap-alternative. Tissues regenerated well within the scaffold during the next 2 months, halving the wound area to 132 cm2. A thick split-skin graft was applied over the remaining granulating neodermis, which “took” completely. Six months postoperatively, the patient regained most hand functions and performed all activities satisfactorily, while the grafted area appeared almost identical to surroundings. Minimally invasive reconstruction thus produced satisfying results with fewer shorter simpler surgeries, minimal anesthesia, short-duration hospitalization, lower health care costs, lesser risks, and excellent patient-reported outcomes.