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Matrix Engineering Matrix Engineering A New Concept of A New Concept of Treatment for Skin Treatment for Skin
RejuvenationRejuvenationDr Patrick J. Treacy Dr Patrick J. Treacy
Ailesbury ClinicAilesbury Clinic
Dublin Dublin
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MEDICAL DISCLOSURE:
Dr. Patrick J. Treacy is a Cosmetic Doctor Dr. Patrick J. Treacy is a Cosmetic Doctor registered in UK and Ireland registered in UK and Ireland
I have previously been registered in United I have previously been registered in United States, Australia, New Zealand and South Africa.States, Australia, New Zealand and South Africa.
I have no financial interest or stock in I have no financial interest or stock in BIoPolymer GmbH & Co KG BIoPolymer GmbH & Co KG
I receive no additional remuneration for stock I receive no additional remuneration for stock bought by you after attendance at this lecturebought by you after attendance at this lecture..
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Matrix EngineeringMatrix Engineering
Any new tissue formation such as Any new tissue formation such as collagenesiscollagenesis in the in the dermal compartment of the skin is dependant on many dermal compartment of the skin is dependant on many different factors: different factors:
Cells, Cytokines and Extra Cellular Matrix (ECM ).Cells, Cytokines and Extra Cellular Matrix (ECM ).
The verification of new collagen after a special treatment The verification of new collagen after a special treatment is demonstrated by High Frequency Echo Sounder as a is demonstrated by High Frequency Echo Sounder as a non-invasive instrument for clinical research.non-invasive instrument for clinical research.
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Cells Cytokines
Molecular Dermal Biology
Extra Cellular Matrix( ECM )
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Methods and SystematicsMethods and Systematicsof Dermal Matrix Engineeringof Dermal Matrix Engineering
StimulationCollagenesisMicrobeads
New tissueformation
Collagen type I
Substitutionof
Hyaluronic acid
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TreatmentINTRADERMAL
Wrinkles, folds, lip augmentation, lip contour, glabella, naso-labial, fine lines
You can use the same product only changing the needle!
22
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Matrix EngineeringMatrix Engineering = = Augmentation + RegenerationAugmentation + Regeneration
Immediate excellent Immediate excellent augmentationaugmentation of of wrinkles and foldswrinkles and folds
because of the because of the HylanGel CopolymerHylanGel Copolymer
(RHAI technique).(RHAI technique).
Evidence that the Evidence that the positively charged positively charged microbeads leads to microbeads leads to the creation of new the creation of new collagen and for a collagen and for a regenerationregeneration of the of the dermis.dermis.
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The RHAI – techniqueThe RHAI – technique
By cross-linking sodium hyaluronate a By cross-linking sodium hyaluronate a RReticulated eticulated HHyaluronic yaluronic AAcid cid IImplant ( RHAI ) is mplant ( RHAI ) is designed.designed.
In combination with naturally hyaluronic acid and In combination with naturally hyaluronic acid and hypromellose a viscoelastic co-polymer is hypromellose a viscoelastic co-polymer is created for biomedical matrix engineering.created for biomedical matrix engineering.
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Essentials required for the size and Essentials required for the size and texture of particulate materialtexture of particulate material
Spherical microspheres or microbeadsSpherical microspheres or microbeads
Minimum diameter should be 40 µMinimum diameter should be 40 µ
Smooth, homogeneous surfaceSmooth, homogeneous surface
Liquid biocompatible mediumLiquid biocompatible medium
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Interaction of cells/tissue with Interaction of cells/tissue with microparticlesmicroparticles
Macrophage interaction with the biomaterialMacrophage interaction with the biomaterial
Leads to acute and chronic inflammationLeads to acute and chronic inflammation
Results in formation of a fibrous capsuleResults in formation of a fibrous capsule
Leads to new collagen formationLeads to new collagen formation
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Interaction of cells/tissue with Interaction of cells/tissue with microparticlesmicroparticles
These effects are related toThese effects are related to
SurfaceSurface SSmoothmooth
SizeSize 40 to 150 µm40 to 150 µm
ShapeShape SSphericalpherical
Structure BStructure Biocompatibleiocompatible
CarrierCarrier LLiquid mediumiquid medium
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Different Shape and Surface structureDifferent Shape and Surface structureof microparticlesof microparticles
Irregular shape +Irregular shape +
Rough surface structureRough surface structure
resulted in:resulted in:
Foreign body reactionForeign body reaction
Regular shape+Regular shape+
Smooth surface Smooth surface
resulted in:resulted in:
Fibrous tissue with Fibrous tissue with
neocollagenesisneocollagenesis
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Migration of particlesMigration of particlesin the dermal compartmentin the dermal compartment
The critical particle The critical particle size to avoid the size to avoid the phenomenon of phenomenon of migration is migration is 80 to 80 to 120 120 µmµm
The extracellular The extracellular migration caused by migration caused by mechanical forces mechanical forces (muscle movement, (muscle movement, gravity) is called gravity) is called dislocationdislocation
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Types of MicroparticlesTypes of Microparticles
PermanentPermanent
PolymethylmethacrylatePolymethylmethacrylate
PolyvinylhydroxidPolyvinylhydroxid
BiodegradableBiodegradable
DextranomereDextranomere
Hylan Gel particle (xHA)Hylan Gel particle (xHA)
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Matrix EngineeringMatrix Engineeringwith with MatridexMatridex
MatridexMatridex is a new resorbable gel-suspension is a new resorbable gel-suspensionfor the treatment of skin defects (wrinkles).In for the treatment of skin defects (wrinkles).In comparison to all other fillers, it works with two comparison to all other fillers, it works with two effects:effects:
1.1. Replacement of lost hayluronic acid Replacement of lost hayluronic acid ((augmentationaugmentation))
2.2. New formation of collagenous tissueNew formation of collagenous tissue((regenerationregeneration))
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CompositionComposition
1 ml 1 ml MatridexMatridex contains: contains:
Hyaluronic acidHyaluronic acid 25 mg25 mg
Hylan GelHylan Gel 25 mg25 mg
HypromellosHypromellos 15 mg15 mg
DEAE SephadexDEAE Sephadex 25 mg25 mg
CE 1275CE 1275
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Hylan GelHylan GelCrosslinked hyaluronic acidCrosslinked hyaluronic acid
BiocompatibleBiocompatible
Non-tissue reactiveNon-tissue reactive
Non-antigenicNon-antigenic
High hydration levelHigh hydration level
Water insolubleWater insoluble
Hyaluron, its Crosslinked Hyaluron, its Crosslinked Derivates – Hylan – and their Derivates – Hylan – and their Medical Application,Medical Application,
Balazs, Leshchiner, 1989Balazs, Leshchiner, 1989
Hylan Gel Biomaterial: Dermal Hylan Gel Biomaterial: Dermal and immunologic compatibility,and immunologic compatibility,
Larsen,Pollack,Balazs, 1993Larsen,Pollack,Balazs, 1993
In vitro In vitro Cytotoxicity ReportCytotoxicity Report
BioService Project No. 021863,BioService Project No. 021863,
20022002
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Hypromellose GelHypromellose Gel
Hydroxypropylmethyl-Hydroxypropylmethyl-cellulose (HPMC)cellulose (HPMC)
BiocompatibleBiocompatible
ViscoelasticViscoelastic
Non-inflammatoryNon-inflammatory
Chemical and physical properties Chemical and physical properties of Methocel(HPMC) and ist clinical of Methocel(HPMC) and ist clinical useuse
Kamman, 1997Kamman, 1997
Studies of Irritating Action of Studies of Irritating Action of MethylcelluloseMethylcellulose
Fleming, 1959Fleming, 1959
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DextranomereDextranomere
Crosslinked DextranCrosslinked Dextran
BeadsBeads
SphericalSpherical
Size from 80µ - 125µSize from 80µ - 125µ
Charged surfacesCharged surfaces
- positively - positively (Matridex/DEAE Sephadex)(Matridex/DEAE Sephadex)
- negatively- negatively
Regulatory support file Sephadex,Regulatory support file Sephadex,
Pharmacia, 2002Pharmacia, 2002
Regulatory support file DEAE Regulatory support file DEAE Sephadex, Pharmacia, 2002Sephadex, Pharmacia, 2002
Regulatory support file CM Regulatory support file CM Sephadex, Pharmacia, 2002Sephadex, Pharmacia, 2002
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DextranomereDextranomereTradename: SephadexTradename: Sephadex
Neutral, uncharged beadsNeutral, uncharged beads 40-60 µ leads to migration 40-60 µ leads to migration and and granuloma formation granuloma formation
Negatively charged CM beadsNegatively charged CM beads stimulating osteogenesis, new stimulating osteogenesis, new bone formationbone formation
Positively charged DEAE beadsPositively charged DEAE beads 80-125 µ no migration, 80-125 µ no migration, stimulation of collagenesis stimulation of collagenesis
Heel,R.C.,Morton,P.,Brogden,R.N.: „Dextranomere. A review of ist Heel,R.C.,Morton,P.,Brogden,R.N.: „Dextranomere. A review of ist general properties and therapeutic efficacy.“general properties and therapeutic efficacy.“
Drugs 1979;18:89-102Drugs 1979;18:89-102
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BiocompatibilityBiocompatibility
BiocompatibleBiocompatible
BiodegradableBiodegradable
Non-sensitizationNon-sensitization
Non-cytotoxicityNon-cytotoxicity
Biocompatible viscoelastic gel Biocompatible viscoelastic gel slurries, their preparation and slurries, their preparation and useuseLeshchiner, 1991Leshchiner, 1991Implantation study of MatridexImplantation study of MatridexHistology reportHistology reportISO 10993-6, 2002ISO 10993-6, 2002Cytotoxicity Assay MatridexCytotoxicity Assay MatridexISO 10993-5, 2002ISO 10993-5, 2002Sensitization Assay MatridexSensitization Assay MatridexISO 10993-10, 2002ISO 10993-10, 2002
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PerformancePerformanceTransfer of collagen-Transfer of collagen-stimulating stimulating substancessubstances
Transfer of skin Transfer of skin hydrating substanceshydrating substances
Transfer of skin Transfer of skin regenerating regenerating substancessubstances
Enhanced Healing of cutaneous Enhanced Healing of cutaneous wounds using beads with positively wounds using beads with positively charged surfacescharged surfacesMustoe, 1992Mustoe, 1992
Comparative rheological behavior of Comparative rheological behavior of Hyaluronan from bacterial and animal Hyaluronan from bacterial and animal sources with crosslinked Hyaluronan sources with crosslinked Hyaluronan (Hylan Gel) in aqueous solution(Hylan Gel) in aqueous solutionMilas, 2001Milas, 2001
Biocompatible visvoelastic slurries, Biocompatible visvoelastic slurries, their preparation and usetheir preparation and useLarsen, 1991Larsen, 1991
Implantation Assay Matridex Implantation Assay Matridex BioService Report No. 021627, 2002BioService Report No. 021627, 2002
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StartseiStartseitete
INDICATIONS AND INSTRUCTIONS FOR USE
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PRE/POST LIP AUGMENTATION
Injecting technique:When using Matridex or Matridurit is recommanded only injecting in the vermillion border zone. Not from the inner site of the lips ( vestibulum ).
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Histology Report 3/52Histology Report 3/52
INTERMATERIAL SPACEINTERMATERIAL SPACE
Small collagen fibre bundles Small collagen fibre bundles (1 to 10(1 to 10µm in width)µm in width)
Capillaries and fibroblastsCapillaries and fibroblasts
Macrophages are in close Macrophages are in close apposition to the beads.apposition to the beads.
Sirius red and blue, OM 100 xSirius red and blue, OM 100 x
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Histology Report 1yearHistology Report 1year
Extensive fibroblast and Extensive fibroblast and collagen exist in the collagen exist in the intermaterial spaceintermaterial space
Absence of neutrophilic Absence of neutrophilic or lymphocytic infiltrate.or lymphocytic infiltrate.
Hematoxylin and eosin, OM 40 xHematoxylin and eosin, OM 40 x
Fig. 3Fig. 3
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1 year after Implantation
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No Skin Test RequiredNo Skin Test Required
Non-animal origin of the raw materials in Non-animal origin of the raw materials in Matridex and Matridur (ex fermentation).Matridex and Matridur (ex fermentation).
The basic hyaluronic acid (HA) contains The basic hyaluronic acid (HA) contains only 0.025 I.U./mg of Endotoxins. only 0.025 I.U./mg of Endotoxins.
Highest purity for Hyaluronic acid (HA)Highest purity for Hyaluronic acid (HA)
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Verification of New Collagen after Treatment
High Frequency Echo Sounder
Collagenoson DLXMA
TR
IDEX
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VERIFICATION OF NEOCOLLAGENESIS
Face-Measurements with the Minhorst- Collagenoson before/after Matridex implantation
1 Minute after implantation 3 weeks after implantation
NEW COLLAGEN
18 months after implantation
NEW COLLAGEN REMAINS
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Implantation intradermal
bevel of the needle up
slight molding after implantation
repetition after 3 weeks is recommanded ( cumulative effect of the stimulation )
ImplantationImplantation
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1 year after Implantation
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SCHLUSSBILD
MATRIDEX + MATRIDURTHE NEW GENERATION OF BIOMATERIAL IMPLANT
BioPolymer GmbH & Co.KGGermanyE-mail [email protected]