Plastic and Reconstructive Surgery Research & Innovation Division

Microsurgery and Plastic Surgery laboratory

Our Vision

The mission of our laboratory is to bring scientists and clinicians to collaborate and develop new therapeutic strategies in the fields of wound healing, tissue repair and tissue regeneration with the main goal of successfully applying these into clinical practice. In the framework of our laboratory plastic surgeons, biologists and bioengineers work together in various investigative fields:

  • Cryopreservation of compound tissues, limbs and organs and application of cryopreserved tissues for microsurgical reconstruction.
  • Application of the mesenchymal stem cells, including adipose-derived stem cells, in wound healing, tissue repair and regeneration.
  • Bacterial biofilm and its implication on breast implants and irradiation-induced breast implant capsular contracture.
  • Effects of ischemia, diabetes and aging on wound healing mechanisms
  • Application of hyperbaric oxygen therapy for enhancement of tissue regeneration.
  • Reconstructive transplantation and development of innovative clinical solutions for transplant recipients.

 

CORE FACILITIES & SHARED RESOURCES

  • Patient-derived biological samples
    Capsule, adipose, skin, blood
  • Translational Research Laboratory
    In vitro and in vivo experimental models
  • Clinical data & outcomes
    Databases, imaging, PROMs, AI
  • Molecular & histological analysis
    Mechanistic and translational endpoints
    Innovation & collaboration
    Clinical-tech and industry interfaces

Team

Prof. Yoav Barnea, MD

HEAD OF THE DEPARTMENT

Inna Solodeev, PhD

DIRECTOR, RESEARCH & INNOVATION DIVISION

Orel Govrin, MD

DIRECTOR OF BASIC & PRECLINICAL RESEARCH

Ehud Fliss, MD

DIRECTOR OF CLINICAL RESEARCH

RESEARCH UNITS

RESEARCH FOCUS

• Implant-associated capsular contracture
• Radiation-induced fibrosis
• Fibroblast biology and fibrotic mechanisms
• Mesenchymal stromal cells and extracellular vesicles
• Angiogenesis and tissue vascularization
• Nipple-areolar complex preservation

PROJECTS
• MSC-derived extracellular vesicles for prevention of capsular contracture after radiotherapy
• Fibroblast phenotypes in Baker grade IV contracture
• Angiogenesis in breast implant capsular contracture
• Isolation and characterization of capsule-derived cells
• Cryopreservation and delayed grafting of the nipple-areolar complex
• HBOT for radiation-induced capsular contracture
• Pericapsular adipose tissue secretome

RESEARCH TEAM
• Almog Uziel Levin, PhD
Medical Student
• Kylie Geffen, BSc
• Rafael Brzezinski, PhD, MD
• Daniel Levinson, BSc
Medical Student
• Bar Kamchin, BSc
Medical Student

RESEARCH FOCUS
• Peripheral and facial nerve regeneration
• Experimental nerve repair
• Cell-based regenerative therapies
• Schwann cell and axonal regeneration
• Neuromuscular recovery and muscle remodeling

PROJECTS
• Novel technologies for enhancing nerve regeneration and functional recovery
• Mesenchymal stromal cells in peripheral nerve injury models
• Hyperbaric oxygen in nerve regeneration models
• Muscle histopathology in facial synkinesis

RESEARCH TEAM
• Mor Hershkovitz
Medical Student
• Dana Idelson, MD
• Lilach Margalit Grigg, PhD, MD

RESEARCH FOCUS
• Computer vision and 3D analysis of surgical photography and imaging
• Objective assessment of aesthetic, functional and histological outcomes
• Predictive modeling from clinical, operative and imaging data
• Digital phenotyping and wearable-based remote postoperative monitoring
• GPT/LLM tools for surgical assessment, planning and research workflows
• AI-ready clinical databases, image datasets and outcome registries

PROJECTS
• Wearable-based monitoring of breast cancer patients during reconstruction and oncologic treatment
• AI-assisted implant selection after mastectomy using clinical, imaging and operative data
• Computer vision and LLM-based assessment of breast surgery outcomes — symmetry and aesthetic evaluation after reconstruction and reduction mammaplasty
• Predictive modeling of postoperative outcomes and complications from departmental clinical databases
• Deep-learning image analysis for preclinical and histological studies, including NF-200-positive axon detection

RESEARCH TEAM
• Shira Naveh, MD
• Yahav Ochion
Medical Student
• Shachar Klimker
Medical Student

COLLABORATION LABS
o Digital Epidemiology & Health Analytics Lab. Prof. Dan Yamin, Tel Aviv University
o Big Data Lab. Prof. Erez Shmueli, Tel Aviv University
o AI for Precision Health (Glicksberg Lab). Prof. Benjamin Glicksberg, Icahn School of Medicine at Mount Sinai

 

RESEARCH FOCUS
Clinical, prospective and retrospective investigations, focusing on:
• Alloplastic and autologous breast reconstruction
• Microsurgery and perforator-flap reconstruction
• Facial reanimation surgery
• Gender-affirming surgery
• Post-bariatric body contouring surgery
• Pediatric and craniofacial surgery
• Burns reconstruction and scars
• Chest wall reconstruction surgery
• Patient-reported outcomes studies
• Evaluation of new surgical techniques and technologies

PROJECTS
• Prospective clinical trials in direct-to-implant pre-pectoral immediate breast reconstruction
• Retrospective outcomes analysis in immediate breast reconstruction
• BREAST-Q outcomes and 3D volume changes after reduction mammaplasty
• Patient-reported outcomes in gender-affirming surgery
• Free-flap monitoring, cost-effectiveness and new visualization technologies
• Perforator flap-based chest wall and sternal reconstruction
• Hyperbaric oxygen therapy and outcomes of facial reanimation
• Outcomes in craniosynostosis, lipomyelomeningocele, and cleft lip/palate
• Effects of tranexamic acid in post-bariatric body contouring surgery
• Ongoing departmental clinical and patient-reported outcomes database CLINICAL

RESEARCH CONTRIBUTORS
Specialists and residents from the Department of Plastic and Reconstructive Surgery

RESEARCH COORDINATOR
Tal Melnikov

Research

and function of a cryopreserved rat hind limb

Effective cryopreservation of large tissues, limbs and organs has the potential to revolutionize medical reconstruction options following trauma and organ preservation and transplantation procedures. Existing methods for long-term organ and tissue preservation are characterized by significant tissue-size and time limitations. Our work in this field has aimed to develop a novel vitrification-based approach that will enable long-term survival and functional recovery of large tissues and limbs following cryopreservation and transplantation.

We scored undeniable successes in our research: rats were able to walk using the cryopreserved limb and demonstrated nerve regeneration and the return of functional sensation. We continue to develop protocols for long-term preservation of large tissues, limbs, and organs for clinical use.

of stromal vascular fraction (SVF) from adipose tissue

Fresh adipose tissue derived regenerative cells, also called stromal vascular fraction (SVF) can be extracted from fat after liposuction. Currently, SVF is used in the treatment of various clinical conditions – e.g. osteoarthritis, Crohn’s disease related fistulas and more. The current standard for SVF extraction has several significant disadvantages:

  • Time consuming (~1.5 hours) and technically complicated due to the use of enzymatic dissociation of the fat tissue
  • High regulatory burden in the USA and Europe
  • Hight expenditure due to the cost of the GMP grade enzyme
  • Risk of contamination of isolated cells with the digesting enzyme

Our work in this field has led us to develop a novel non-enzymatic SVF extraction system that will provide the following benefits:

  • Fast: 10 minutes to SVF cell enzymatic extraction
  • Sterile: extraction is performed in a closed system with the lipoaspirate suctioned directly into a sterile container (no need for a clean room)
  • Easily used within the surgical arena for immediate cell transplantation
  • We believe that bringing our novel technology to the market will help make SVF therapy safer and more accessible to patients.

by hyperbaric oxygen treatment in the rat sciatic nerve model

Paralysis of the facial muscles causes loss of voluntary facial movements, loss of involuntary facial expression, and dysfunction of facial function. Currently, the gold standard surgical reconstructive procedure for facial paralysis (i.e facial reanimation) includes the use of a cross-face nerve graft. With this method, a nerve graft is transferred from the normal facial nerve to the paretic hemi-face. This allows normal facial nerve axons to sprout and innervate the paretic hemi-face. The major disadvantage of cross-face nerve grafting is that clinical results are inconsistent. The leading cause of failure is suspected to be poor traversing of motor axons from the contralateral facial nerve branches into, across, and out of the nerve graft.

Hyperbaric oxygen treatment is used to provide optimal tissue oxygen tension in order to maintain the neural aerobic metabolism and viability of the tissue, reduce edema, enhance perfusion of the injured tissue, restore axonal transport, enable the necessary delivery of nutrients at the site of injury, accelerate healing, and promote neovascularization.

The aim of our research is to provide a faster regeneration pace and better quality of the regeneration process in a nerve autograft by exposing it to hyperbaric oxygen treatment

‎a ‎therapeutic‎ ‎potency ‎of ‎adipose‎-‎derived‎ ‎mesenchymal ‎stem‎ ‎cells ‎‎(‎MSCs‎)‎

Mesenchymal stem Cells (MSCs) are multipotent cells that are derived from various adult tissues. MSCs therapy represents one of the most innovative approaches in the field of tissue repair therapies. In vitro and in vivo studies proved the MSCs have the ability to secret the trophic factors that promote angiogenesis and remodel the extracellular matrix.  Other mechanisms of action include high immunomodulation capacity of MSCs.

Our previous  studies demonstrated significant immunomodulatory capacity of ligand pre-treated MSCs compared to non-treated cells.

 The current study in the field focuses on improving regeneration capacity of human MSCs in different models.

of antimicrobial preventative protocols in an in-vivo Methicillin resistant staph aureus breast implant infection model

Infection is a troubling complication of implant-based breast reconstruction, especially when biofilm formation causes resistance to antibiotic treatment. Staphylococcus is the most common pathogen in such cases, with rapidly increasing Methicillin resistant staph aureus (MRSA) rates.

The aim of this research is to examine different pocket irrigation protocols and regimens of antibiotic prophylaxis on MRSA biofilm formation in silicone breast implants using a novel rat model.

in non-immune stromal adipose tissue cells and its role in obesity-associated inflammation and insulin resistance development

Metabolic syndrome, which is considered to be induced by visceral obesity, raises the risk of cardiovascular disease and type 2 diabetes (T2D). Adipose tissue inflammation during obesity is suggested to play a central role in T2D initiation and its complications. The NLRP3 protein is part of the inflammasome complex, which is responsible for IL-1β protein activation. NLRP3-inflammasome activation in adipose tissue macrophages (ATMs) during obesity was previously demonstrated to play a major role in obesity-induced inflammation and insulin resistance (IR). However, the contribution of inflammasome activation in the non-immune cell fraction of adipose tissue (NICF-AT) in obesity-induced inflammation and IR remains unknown.

The aim of the study is to research the role NICF-AT inflammasome activation in the development of obesity induced fat inflammation and IR.

Highlight Publications

A novel two-stage vitrification procedure enables long-term survival and function of a cryopreserved rat hind limb. 

Arav A, Li S, Freidman O, Soledeev I, Aouizerate J, Gur E and Shani N.

Nature Communications. Under review.

Comparing the efficacy of antimicrobial preventative protocols in an in-vivo MRSA breast implant infection model.

Dina Gofstein-Hayuth, Yoav Barnea, Carolina Legarda, Anat Lerner, Jonathan Lellouche, Gal Bracha, Zack Shiloah, Yehuda Carmeli, Eyal Gur, Nir Shani and Ehud Arad.

In preparation.

A clinical hyperbaric oxygen treatment protocol enhances sciatic nerve regeneration in a rat model.

Kedar D, Efrati S, Gur E and Shani N.

In preparation.

FasL Promotes Proliferation and Delays Differentiation of ASCs.

Ina Sarel, Galina Rodionov, Amos Ofer, Michal Rosenzwaig, Michal Shrift Tzadok, Anastasia Rodin, Ela Bar Or, Ahmi Ben-Yehudah, Inna Solodeev, Nir Shani, Shai Yarkoni.

Japan Journal of Medicine. 2021;Feb 4(1): 474- 483.

Reduced culture temperature attenuates oxidative stress and inflammatory response facilitating expansion and differentiation of adipose-derived stem cells.

 Tirza G and Solodeev I, Sela M, Greenberg I, Pasmanik-Chor M, Gur E and Shani N.

Stem Cell Research & Therapy. 2020 Jan 23;11(1):35.

Cryopreservation of stromal vascular fraction cells reduces their counts but not their stem cell potency.

 Solodeev I, Orgil M, Bordeynik-Cohen M, Meilik B, Manheim S, Volovitz I, Sela M, Inbal A, Gur E, and Shani N.

 Plast Reconstr Surg Glob Open. 2019 Jul 5;7(7):e2321.

Cryopreservation and transplantation of vascularized composite transplants: unique challenges and opportunities.

Shani N, Friedman O, Arav A, Natan Y and Eyal Gur.

Plast Reconstr Surg. 2019 May;143(5):1074e-1080e.

Incomplete Facial Paralysis: The Use of the Ipsilateral Residual Facial Nerve as a Donor Nerve for Facial Reanimation.

Eyal Gur, Ron M. Zuker, Arik Zaretski, David Leshem, Yoav Barnea, Ehud Arad, Ravit Yanko, Benjamin Meilik, Daniel J. Kedar, Ehud Fliss,

Plastic and Reconstructive Surgery.  2018 Jul;142(1):202-214.

Fas-L promotes the stem cell potency of adipose-derived mesenchymal cells.

Inna Solodeev, Benjamin Meilik, Ilan Volovitz, Meirav Sela, Sharon Manheim, Shai Yarkoni, Dov Zipori, Eyal Gur and Nir Shani.

Cell Death and Disease. 2018 Jun 11;9(6):695.

Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model.

Friedman O, Carmel N, Sela M, Abu Jabal A, Inbal A, Ben Hamou M, Krelin Y, Gur E and Shani N.

PLoS One. 2017 Jul 26;12(7):e0181507

Rat hindlimb cryopreservation and transplantation – A step towards “organ banking”.

Arav A, Friedman O, Natan Y, Gur E and Shani N.

 

 

 

Am J Transplant. 2017 Nov;17(11):2820-2828.