Dennis Orgill, MD, PhD
Professor of Surgery, Harvard Medical School
Principle Investigator, Would Healing & Tissue Engineering Laboratory
Brigham and Women’s Hospital
75 Francis Street
Boston, MA 02115
Fax: (617) 730-2855
Wound Healing and Tissue Regeneration
Scaffolds and Biomaterials
Fat Grafting, Adipose tissue and Adipose-Derived Stem Cells
Please contact PI or Administrative Assistant
“Mechanical Forces to Augment Fat Grafting”
11/08/2013 – 11/07/2017
The major goals of this project are to study the effects of external suction on recipient sites before fat grafting.
“Examining the effects of ABCB5+ dermal stem cells on cutaneous wound healing”
7/1/2014 – 6/30/2016
The major goals of this project are to investigate the role of ABCB5+ cells in wound healing.
“Augmentation of MTF Adipose Scaffold Effects with Mechanical Forces”
7/1/2014 – 6/30/2015
The major goals of this project are to study the effects of mechanical forces on adipose-tissue scaffolds in vivo.
Our laboratory is located in the Longwood Medical Area of Boston, a high density region of research institutions, teaching hospitals and universities, which helps foster a collaborative environment. The state-of-the-art Tissue Engineering and Wound Healing Laboratory is housed in the 16-story biomedical Thorn building jointly funded by the Brigham and Women’s Hospital, Harvard Medical School and the Howard Hughes Medical Institute. The lab is over 500 sq ft, which is part of a larger 16,000 sq ft shared lab facility and has facilities for mathematical modeling, Q-RT-PCR machines for molecular biology analysis, immunohistochemistry, FACS, Optimal Microscopy, small and large animal surgery, cell cultures, fabrication of collagen matrices, molecular biology analysis, micromechanical forces studies, platelet studies.
The small and large animal facilities within the Brigham and Women's Hospital/Harvard Medical School include standard or BL-2 murine barrier facility, housing for small and large animals, a dedicated room for housing pigs, surgical suites for small and large animal surgeries (including microsurgical equipment for flap surgery and all required equipment for anesthesia, intra-operative or post-operative monitoring of animals), an animal disposal area and animal supply rooms.
External Volume Expansion (EVE) of Soft Tissues
Over the last several years pioneers in fat grafting have achieved impressive clinical results through the use of mechanical forces to better prepare the recipient site in both breast augmentation and breast reconstruction. It is theorized that mechanical stimulation directly stimulates angiogenesis through the induction of a short term edematous state, as well as provides a more suitable recipient bed for fat grafting. Past work from our laboratory has shown changes in vasculature as a result of application of mechanical forces in both skin stretching and the use of the V.A.C.® device. Recent evidence using mechanical stimulation in our mouse model suggests that such suction-based multidirectional mechanical stimulation of non wounded tissues can change the cutaneous vasculature, with the overall effect of improving the quality of a recipient graft site for fat injection. Our hypothesis is that mechanical stimulation can be used to increase the vasculature of the recipient site, resulting in the increases survival of fat grafts as well as allowing higher volume fat injections. Recently, we have described an external volume expansion (EVE) device that mimics the biology of the commercially available EVE device known as BRAVA. We are now further developing our model to determine how to maximize survival of grafted adipose tissue by optimal preconditioning (pattern, pressure and duration of treatment) of the recipient site through mechanical stimulation. We are confident that EVE represents a valuable strategy for recipient site preconditioning and it will pave the way for more effective clinical application of fat grafts in soft tissues reconstruction.
Application of Dermal Stem Cells for Promotion of Healing in Chronic Wounds
Chronic ulcers, burns and severe traumatic wounds pose a dramatic problem for a growing number of patients worldwide, constituting a remarkable burden for health care systems. Mesenchymal stem cells (MSCs) hold a promising therapeutic potential in wound healing. The purpose of this study is to define this potential and translate it to clinical application to provide an effective treatment for patients affected by chronic/severe wounds. ABCB5+ are special MSCs (A-MSCs) present in large quantities in the dermis. Our preliminary preclinical studies have shown that these cells accelerate tissue repair in vivo. We are investigating the therapeutic potential of human A-MSCs combined to regenerative dermal scaffolds in a murine wound healing model. Our central hypothesis is that A-MSCs are major inducers of tissue regeneration through promotion of angiogenesis: dermal regenerative scaffold will boost their regenerative attitude by providing an ideal environment for cell engraftment and proliferation. Overall, we envision that this research will provoke a paradigm shift in clinical application of allogeneic MSCs for wound healing.
Combining Adipose Tissue Scaffolds, Adipose Derived Stem Cells and Mechanical Forces for Soft Tissue Regeneration
Fat grafting is revolutionizing plastic surgery and it has been highly effective in breast reconstruction, breast augmentation, facial contour defects, radiation defects and chronic wounds. Our group also has 35 years of experience working on dermal scaffolds for skin regeneration and is now committed to extend this expertise in the field of adipose tissue regeneration. The focus of research in this area has mostly been on adipose derived stem cells (ADSCs), largely neglecting the potential of mechanical forces and scaffolds as adjuncts in these procedures. The goal of our study is to define the potential of decellularized adipose scaffolds combined with ADSCs and mechanical forces to enhance soft tissue augmentation and regeneration. Our preliminary studies have shown that mechanical forces stimulate adipogenesis, support fat survival and proliferation. We are now integrating this knowledge with that gained in tissue engineering and stem cells research. We believe that the combination of all these treatments represent the most ideal strategy to achieve the most effective clinical outcomes.
1. Yannas IV, Burke JF, Orgill DP, Skrabut EM, inventors. US patent 4,418,691. 1983 Dec 6 “Method of Promoting the Regeneration of Tissue at a Wound”
2. Yannas IV, Orgill DP, Loree HM, II, Kirk JF, Chang ASP, Mikic BB, Krarup C, Norregaard TV. US Patent 4,955,893. 1990 Sep 11 “Prosthesis for Promotion of Nerve Regeneration”
3. Orgill DP, Butler CE, Barlow M, Ritterbush S, Yannas IV, Compton CC. US Patent 5,489,304. 1996 Feb 6 “Method of Skin Regeneration Using a Collagen-Glycosaminoglycan Matrix and Cultured Epithelial Autograft”
4. Orgill DP, Butler CE, Barlow M, Ritterbush S, Yannas IV, Compton CC. US Patent 5,716,411. 1998 Feb 10 “Method of Skin Regeneration Using a Collagen-Glycosaminoglycan Matrix and Cultured Epithelial Autograft”
5. Orgill DP, Mulliken J, Ehret F. US Patent 6,117,444. 2000 Sep 12 “Polyethylene Glycol/Microfibrillar Collagen Composite Serves as a Resorbable Hemostatic Agent”
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