D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)

Inclusion Criteria: 1. Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision that is \>20cm (target incision). 2. Subjects are preoperative hemodynamically stable. (BP≤180/110 and \>90/60 mmHg, and HR≤120 and \>60 bpm, and temperature ≤37.50C and \>35.50C). 3. Male or non-pregnant female. 4. Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure. 5. Subjects' age 18 years old and above at screening. 6. Subjects who sign the written Informed Consent Form. 7. Subjects who are willing and able to participate and meet all study requirements. 8. Survival expectancy of at least 60 days post randomization. Exclusion criteria: 1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, etc.) 2. Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization. 3. Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past 1 week prior to randomization, excluding pre-operative prophylaxis. 4. Subjects undergoing concomitant major procedures in addition to the colorectal resection. Female sterilization surgeries (i.e. salpingo-oophorectomy etc.), involvement of a small bowel procedure or cholecystectomy may be allowed, pending an advanced consultation and approval from the Sponsor . 5. Subjects who received any anti-cancer treatment within the last 4 weeks of surgery. 6. Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, within the last 4 weeks of the planned abdominal surgery. 7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past 4 weeks prior to randomization. 8. Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients. 9. Subjects with known allergies to more than 3 substances (an allergy questionnaire will be completed during the screening process). 10. Subjects with history of severe allergic reaction to any substance, having required treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion of the PI is at high risk of developing severe allergic reactions. 11. Subjects with End Stage Renal Disease (ESRD/ CKD stage 5). 12. Subjects with severe hepatic impairment. 13. Subjects with chronic urticaria. 14. Subjects diagnosed with CVA within the past 6 months prior to randomization. 15. Subjects who underwent any abdominal surgery and current planned index surgery involves re-opening the scar of a prior abdominal surgery performed within the last 3 years. 16. Any subject with an active malignancy or with malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least 3 years. Excluding: Subjects with potentially resectable non-metastatic colorectal cancer, that is the reason for the index surgery. Subjects who have had carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin. Subjects with any additional non-violent cancer that does not require treatment 4 weeks prior to the surgery, and throughout the entire study duration. 17. Subjects with other concurrent severe and/or uncontrolled medical condition. 18. Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study. 19. Chronic alcoholic or drug abuse subjects. 20. Pregnant or breast-feeding women or women of child-bearing age who refuse or are prohibited of using an effective contraceptive method of birth control throughout study participation, including the safety follow-up period. 21. Subjects who received any investigational drug within 30 days or 5 half-lives prior to randomization to the study (whichever is longer) and through the study. 22. Subjects participating in any other interventional study. 23. Subjects who in the opinion of Investigator, are not eligible to participate in the study and/or to comply with the protocol requirements (e.g. due to a cognitive or medical condition).