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

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..

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.

Cells Cytokines

Molecular Dermal Biology

Extra Cellular Matrix( ECM )

Methods and SystematicsMethods and Systematicsof Dermal Matrix Engineeringof Dermal Matrix Engineering

StimulationCollagenesisMicrobeads

New tissueformation

Collagen type I

Substitutionof

Hyaluronic acid

TreatmentINTRADERMAL

Wrinkles, folds, lip augmentation, lip contour, glabella, naso-labial, fine lines

You can use the same product only changing the needle!

22

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.

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.

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

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

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

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

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

Types of MicroparticlesTypes of Microparticles

PermanentPermanent

PolymethylmethacrylatePolymethylmethacrylate

PolyvinylhydroxidPolyvinylhydroxid

BiodegradableBiodegradable

DextranomereDextranomere

Hylan Gel particle (xHA)Hylan Gel particle (xHA)

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))

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

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

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

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

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

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

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

StartseiStartseitete

INDICATIONS AND INSTRUCTIONS FOR USE

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 ).

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

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

1 year after Implantation

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)

Verification of New Collagen after Treatment

High Frequency Echo Sounder

Collagenoson DLXMA

TR

IDEX

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

Implantation intradermal

bevel of the needle up

slight molding after implantation

repetition after 3 weeks is recommanded ( cumulative effect of the stimulation )

ImplantationImplantation

1 year after Implantation

SCHLUSSBILD

MATRIDEX + MATRIDURTHE NEW GENERATION OF BIOMATERIAL IMPLANT

BioPolymer GmbH & Co.KGGermanyE-mail matridex@aol.com