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Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation Queen Victoria Hospital
East Grinstead
West Sussex
Dr. Yella Martin
Postdoctoral Fellow
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation
• Founded in 1961
• BMRF is an independent research institute
• We work closely with surgeons at the Burns unit at Queen Victoria
Hospital to identify/address clinical needs
• Translational unit with focus on:
– Skin
– Fat/adipose tissue
– Cornea
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation
Tissue Regeneration and Repair
Tissue Engineering
Overview of Research Projects
Upcoming Projects
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Tissue Regeneration
What is the difference between repair and regeneration?
Repair is the adaptation to loss of tissue and leaves
behind scar tissue.
Regeneration restores the missing organ mass and
re-establishes structure and function.
Mason, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Skin provides the protective barrier to the environment
– Water retention
– Prevention of infection
• Skin can self-repair to a certain extent
but it cannot fully regenerate
• Wound healing has three stages:
– Inflammation
– Proliferation
– Tissue remodelling
Gurtner, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Skin provides the protective barrier to the environment
– Water retention
– Prevention of infection
• Skin can self-repair to a certain extent
but it cannot fully regenerate
• Wound healing has three stages:
– Inflammation
– Proliferation
– Tissue remodelling
Gurtner, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Skin provides the protective barrier to the environment
– Water retention
– Prevention of infection
• Skin can self-repair to a certain extent
but it cannot fully regenerate
• Wound healing has three stages:
– Inflammation
– Proliferation
– Tissue remodelling
Gurtner, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Skin provides the protective barrier to the environment
– Water retention
– Prevention of infection
• Skin can self-repair to a certain extent
but it cannot fully regenerate
• Wound healing has three stages:
– Inflammation
– Proliferation
– Tissue remodelling
Gurtner, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Skin provides the protective barrier to the environment
– Water retention
– Prevention of infection
• Skin can self-repair to a certain extent
but it cannot fully regenerate
• Wound healing has three stages:
– Inflammation
– Proliferation
– Tissue remodelling
• Small superficial wounds can heal without scarring
• Larger, deeper wounds heal with scarring and
may require surgical intervention
• Chronic wounds require specialist care
Gurtner, et al. (2008)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin
• Scarring can significantly affect appearance and function
• Current treatment options:
– Dressings
– Skin graft
– Meshed skin graft
– Artificial skin replacements
– Autologous/allogeneic cell therapy
Skin graft Meshed skin graft Dermal replacement Autologous cell therapy
Skin graft mesher
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Fat/adipose tissue
• White adipose tissue stores lipids
• Adipose-derived stem cells have the ability to regenerate adipocytes
• When entire fat pads are missing, adipose tissue cannot regenerate:
– Burn injuries
– Trauma, such as explosions or traffic accidents
– Tumour resection
• Soft tissue loss can have a significant affect on
appearance and function at the affected site
• Current treatment options:
– Tissue transplants (flaps)
– Synthetic implants
– Injection of autologous adipose cells (lipoaspirate)
Gesta, et al. (2007)
Mauer, et al. (2010)
Choi, et al. (2010)
Mariman, et al (2011)
Pre-adipocyte Adipocyte
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Tissue Engineering
Tissue engineering is an interdisciplinary
field that applies the principles of
engineering and the life sciences toward the
development of biological substitutes that
restore, maintain, or improve tissue function.
Langer and Vacanti (1993)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Regenerative Medicine/Tissue Engineering
Regenerative medicine/tissue engineering research includes the
following areas:
– Development of novel biomaterials/scaffolds
– Identification of optimal cell sources
– Biomolecules
– Engineering Methods and Design
– Functional assessment of regenerated/engineered tissues
– Informatics as applied to tissue engineering
National Institute for Biomedical Imaging and Engineering (2004)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation Projects
Skin Treatment of burns
Improve healing
Reduce scarring
Fat/soft tissue Replacement and regeneration of missing tissue contours
Eye Regeneration of the limbus and the cornea
Skin cancer Detection
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Skin: Massive burns leave little viable skin for grafting
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Sprayed keratinocytes
or
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Cells delivered in suspension
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Improvement of skin cell culture for patients
• Current practice: keratinocytes are grown in the presence of lethally
irradiated mouse dermal cells.
• Replace mouse dermal cells with human dermal cells from same
patient: Jubin et al. (2011)
• Screen medium formulations to identify alternative methods for cell
expansion.
This will allow us to change current clinical practice and make
treatments safer for patients.
Current medium Human dermal cells New medium 1 New medium 2
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Sprayed keratinocytes
or
This technique has limitations as cells do not recover well
from being put into solution.
How can we overcome this?
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Microcarriers to improve wound healing
Microcarrier Covered with cells
Keratinocytes can be grown on small gelatin microcarriers and delivered
directly to the wound bed.
Martin, et al. (2011)
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Microcarriers to improve wound healing
Skin graft Microcarriers
Treatment of wounds with keratinocytes
on microcarriers resulted in skin repair
that was comparable to a skin graft.
Wounds contract as they heal, and scars can
form. Wounds treated with keratinocytes on
microcarriers contracted less than those
treated with skin grafts, p=0.05.
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Nanofibres to reduce scarring
Fibroblasts align along the orientation of the
nanofibres, cytoskeletal actin (red), focal
adhesions (green). By modulating the
behaviour of fibroblasts we hope to reduce
the amount of contraction that occurs during
healing.
Aligned Random
Fibroblasts
Contractures can form during wound
healing. They can be very painful and
restrict mobility. Contraction is thought to
occur by a combination of specialised
fibroblast cells and tensile forces across
the wound.
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
FAT/SOFT TISSUE: Reconstruction of soft contours
• Adipose/soft tissue can be lost due to:
– Burn injuries
– Trauma, such as explosions or traffic accidents
– Tumour resection
• Soft tissue loss can have a significant affect on appearance and function at the affected site
• Soft tissue injury before and after surgery
• Loss of contour is evident 1 year post surgery
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Use of adipose-derived stem cells (ADSCs)
ADSCs in culture ADSCs on microcarriers
a b
c d
(a, b) Microcarriers with ADSCs remained in the
tissue at 2 weeks after implantation. (c, d) GFP
(green) shows cells that were labelled prior to
transplantation, DAPI (blue) shows cell nuclei.
GFP DAPI
Excised fat or liposuction
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Soft tissue sponges
a b c
1cm 1cm 1cm
Porous soft sponges made from alginate/collagen seeded with ADSCs.
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation Projects
Skin Treatment of burns
Improve healing
Reduce scarring
Fat/soft tissue Replacement and regeneration of missing tissue contours
Eye Regeneration of the limbus and the cornea
Skin cancer Detection
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Blond McIndoe Research Foundation Upcoming Projects
Skin Detection of infections in burn wounds – development of smart
dressings
Fat/soft tissue Modelling of early events that occur after transplantation – the role of
hypoxia
Eye Development of novel materials to deliver cells for corneal repair
Skin cancer Molecular mechanisms
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
Collaborations vital
Queen Victoria Hospital
University of Brighton
Brighton Sussex Medical School
University College London
Imperial College London
University of Bath/Frenchay Hospital Bristol
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240
BMRF Scientific Team
Professor Di Lawrence-Watt – Director of Research
Dr. Justin Sharpe – Head of Research
Postdoctoral Fellows:
– Dr. Yella Martin
PhD students:
– Elsie Fok, Saikat Ray
Research Assistants:
– Catherine Lenihan
Research technicians:
– Judy Roxburgh, Kasia Jubin, Trevor Eydman
Medical students 2011/12:
– Nicky Stevens, Sam Haddad, Manraj Phull, Tom Kilpatrick,
Kevin Lichtenstein
Blond McIndoe
Research Foundation
Registered Charity
Number: 1106240