, Volume 21, Issue 1, pp 61–78 | Cite as

Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery

  • G. GiatsidisEmail author
  • L. Cheng
  • Anthony Haddad
  • K. Ji
  • J. Succar
  • L. Lancerotto
  • J. Lujan-Hernandez
  • P. Fiorina
  • H. Matsumine
  • D. P. OrgillEmail author
Original Paper


In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.


Angiogenesis Tissue preconditioning Reconstructive surgery Soft tissues Soft tissue reconstruction External volume expansion Suction Mechanical forces Animal models Optimization study Translational medicine Flap Graft Plastic surgery Skin Ischemia 



Authors are grateful for the technical support and contribution provided by Dr. Roberto Bassi, Dr. Mihail Climov, Dr. Federico Facchin, Dr. Fabrizio Mpungu, Dr. Chenyu Huang, Dr. Kimberly Khouri, Dr. Tania Rogalska, Dr. Xingang Wang, Dr. Hamed Zartab. Authors also thank Ms. Andrea V. Moscoso for her administrative contribution.


This study was funded in part from a grant from the Plastic Surgery Foundation to Brigham and Women’s Hospital, a grant from the Gillian Reny Stepping Strong Fund to Brigham and Women’s Hospital, and a grant from KCI, Inc to Brigham and Women’s Hospital. P.F. thanks the Fondazione Romeo and Enrica Invernizzi for the generous support.

Author contributions

All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. In addition, all authors equally took part in the different phases of the study. All authors have seen and agreed to the submitted version of the manuscript and bear responsibility for it. GG: contributed to study concept and design, conducted experimental activities, analysis and interpretation of data, manuscript drafting and revision. LC, KJ and AH contributed to acquisition, analysis and interpretation of data, manuscript drafting and revision. LL and JL contributed to study concept and design. P.F. contributed to acquisition and analysis of data. JS and HM contributed to analysis, interpretation, and representation of data, manuscript drafting and revision. DPO supervised the study in all parts, provided critical revision of data and manuscript.

Compliance with ethical standards

Competing interests

Dr. Orgill is a consultant for KCI, Inc. and receives research funding through a grant from KCI, Inc. to Brigham and Women’s Hospital. All other authors declare no actual or potential conflict of interests: in addition, they disclose no commercial or financial associations, personal or other relationships with other people or organizations that could inappropriately influence the reported manuscript or create a conflict of interest with the information presented. Authors (GG, LL, DO) have filed a patent based on methods described in this manuscript (PCT/US2016/018164: “Methods and Apparatus for Promotion of Angiogenesis and Adipogenesis in Tissues Through the Application of Mechanical Forces”) and holds rights as inventors in accordance with their institutional policies.

Data and materials availability

If data are in an archive, include the accession number or a placeholder for it. Here also include any materials that must be obtained through an MTA. Acknowledgments follow the references and notes but are not numbered.

Supplementary material

10456_2017_9586_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)
10456_2017_9586_MOESM2_ESM.pdf (12.9 mb)
Supplementary material 2 (PDF 13,185 kb)


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • G. Giatsidis
    • 1
    • 2
    Email author
  • L. Cheng
    • 1
    • 3
  • Anthony Haddad
    • 1
  • K. Ji
    • 1
    • 4
  • J. Succar
    • 1
    • 5
  • L. Lancerotto
    • 1
    • 2
  • J. Lujan-Hernandez
    • 1
  • P. Fiorina
    • 6
    • 7
  • H. Matsumine
    • 1
  • D. P. Orgill
    • 1
    Email author
  1. 1.Tissue Engineering and Wound Healing Laboratory, Department of Surgery, Division of Plastic SurgeryBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Department of Molecular MedicineUniversity of PadovaPaduaItaly
  3. 3.Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s HospitalShanghai Jiao Tong University, School of MedicineShanghaiChina
  4. 4.Department of Plastic SurgeryChina-Japan Friendship HospitalBeijingChina
  5. 5.Preventive MedicineUniversity of New MexicoAlbuquerqueUSA
  6. 6.Nephrology Division, Boston Children’s HospitalHarvard Medical SchoolBostonUSA
  7. 7.International Center for T1D, Romeo ed Enrica Invernizzi Pediatric Clinical Research Center, Department of Biomedical and Clinical Science L. SaccoUniversity of Milan and ASST Fatebenefratelli-SaccoMilanItaly

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