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Massachusetts Institute of TechnologMassachusetts Institute of Technology
Brigham and Women’s HospitalBrigham and Women’s HospitalVA Boston Healthcare SystemVA Boston Healthcare System
2.79J/3.96J/20.441/HST522J2.79J/3.96J/20.441/HST522J
BIOMATERIALSBIOMATERIALS--TISSUE INTERATISSUE INTERA
oo s or n erstan ng t e o ecu aoo s or n erstan ng t e o ecu aand Physiological Bases of the Tissue Reand Physiological Bases of the Tissue Re
ImplantsImplants
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Tissue* + Biomaterial**
Cell + Matrix**
BIOMATERIALS-TISSUE
INTERACTIONS
* Structure comprising cells of the same type
** Solid surface
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Cell + Extracellular MatrCell + Extracellular Matr
In Tissue Engineering ScaffoIn Tissue Engineering Scaffo
Cell + Biomaterial ScaffolCell + Biomaterial Scaffol
CELL-MATRIX INTERACTIO
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•• Control VolumeControl Volume
•• Unit Cell ProcessesUnit Cell Processes
••
•• Tissue Formation and RemodelinTissue Formation and Remodelin
•• oun ea ngoun ea ng n von vo
CONCEPTS FOR UNDERSTAND
BIOMATERIALS-TISSUE INTERA
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Articular Cartilage
Matrix
Extracellular
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40minChondrocytes (P2 Canine) in
Type I Collagen-GAG Scaffol
2 1
3
Courtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.
“Co
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SolubleSoluble
AA
+ So+ SoCell + MatrixCell +
Product
Matrix
Product(Regulator)(Regulator)
UNIT CELL PROCESSES
Concept of a “Control Volume” aroun
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SolubleSoluble
+ So+ SoCell + Matrix
Product
Cell + Matrix
Product(Regulator)(Regulator)
UNIT CELL PROCESSES
Concept of a “Control Volume” aroun
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SolubleSolubleMechanicalMechanical
AALoading (Strain); Subject 2.785Loading (Strain); Subject 2.785
+ So+ SoCell + Matrix
Product
Cell + Matrix
Product(Regulator)(Regulator)
UNIT CELL PROCESSES
Concept of a “Control Volume” aroun
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•• Control VolumeControl Volume
•• Unit Cell ProcessesUnit Cell Processes
••
•• Tissue Formation and RemodelinTissue Formation and Remodelin
•• oun ea ngoun ea ng n von vo
CONCEPTS FOR UNDERSTAND
BIOMATERIALS-TISSUE INTERA
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•• MitosisMitosis
•• MigrationMigration
•• SynthesisSynthesis•• ontract onontract on
•• EndocytosisEndocytosis
UNIT CELL PROCESSES
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•• MitosisMitosis
•• MigrationMigration
•• SynthesisSynthesis•• ontract onontract on
•• EndocytosisEndocytosis
UNIT CELL PROCESSES
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•• MitosisMitosis
•• MigrationMigration
•• SynthesisSynthesis•• ontract onontract on
•• EndocytosisEndocytosis
UNIT CELL PROCESSES
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COLLAGEN-GAG MATRICES: MODEL BIOM
(ANALOGS OF EXTRACELLULAR MA
Investigation of cell interactions (UCPs)
• Type I (bovi
• ype por
• Chondroitin
1mm
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••
Can provide insights into interrelatioCan provide insights into interrelatioamong cell processes.among cell processes.
–– How do mitosis and synthesis interrelateHow do mitosis and synthesis interrelate
––How do mitosis and synthesis relate toHow do mitosis and synthesis relate to
–– How does migration relate to contractionHow does migration relate to contraction
••
CELL – MATRIX INTERACTIONS
COLLAGEN-GAG MATRICES IN V
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Chondrocytes (Passage 2 Canine)
T I ll n- A M rix
Live cell imaging
for a period of 5
hours.
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••
••
MigrationMigration •• yn es syn es s
•• ContractionContraction
CELL – MATRIX INTERACTI
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Chondrocyte (P2 Canine) in a Type I Collagen-G
Mitosis
Photo removed due to
copyright restrictions.
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60 Mean SEM
40 )
30 A
( u
20 D
Effects of Cross-Linking on Chondrocyte P
in Collagen-GAG Matrices
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CELL ± MATRIX INTERACTIONS
Mitosis
Migration
Synthesis
Contraction
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Fibroblasts Migrate Away from Soft SubNIH 3T3 cells are plated on polyacrylamide substrates with a transi
soft side is marked with fluorescent beads (to the left). Cells tur
substrate as they approach the boundary from the stiff side, by re
lamellipodium that crossed the boundary.
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Fibroblasts Migrate Toward Stiff SubstrNIH 3T3 cells are plated on polyacrylamide substrates with a transit
soft side is marked with fluorescent beads (to the left). Cells turn to
stiff side as they approach the boundary from the soft side, by exp
toward the boundary into a leading lamellipodium
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Fibroblasts Migrate Toward Stretching FNIH 3T3 cells are plated on polyacrylamide substrates. Pulling fo
inserting a blunted needle in the substrate near the trailing end of t
the needle away from the cell. Cells switch the direction of migra
secondary protrusions toward the needle into a leading lam
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Fibroblasts Migrate Away from CompressinNIH 3T3 cells are plated on polyacrylamide substrates. Pushing fo
inserting a blunted needle in the substrate near the leading edge of
and moving the needle toward the cell. Cells switch the direction
retracting the leading lamellipodium.
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Migration of Epithelial Cells In Vitro in a Wound H
100 m
© 2001 L. C. Santy and J. E. Casanova. License CC BY-NC-SA..
http://dx.doi.org/10.1083/jcb.200104019
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40min
2 1
3
Chondrocytes (P2 Canine) in a
GAG Matrix: Migration and
J. Zaleskas, et al .,Biomat. 25:1299 (2004)
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Diagram removed due to copyright restrictionsg. n a r , ney nt. : .
Schematic of the modulation of microvascularendothelial cell phenotype during angiogenesis
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•• MitosisMitosis
•• MigrationMigration
••
•• ContractionContraction
CELL –
MATRIX INTERACT
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Protein Synthesis;Protein Synthesis;Proline Incor orationProline Incor oration
ProteoglyProteogly
.15.15
D N
A
D N
A
0.030.03
DHTDHT
UVUV
0.10.1
o u r /
o u r /
0.020.02EDCEDC
0.050.05
n m o l /
n m o l / 0.010.01
00
Effects of Cross-Linking on Chondrocyte in Collagen-GAG Matrices
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CELLCELL – –MATRIX INTERACTMATRIX INTERACT
•• MitosisMitosis
•• MigrationMigration
••
•• ContractionContraction
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-smooth muscle actin-fusion peptide (SMA-FP) inhibits the tensio
fibroblasts on silicone substrates. After washing our of the FP, cells
See video at
http://jcb.rupress.org/content/suppl/2002/05/03/jcb.20020
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Chondrocytes (P2 Canine) in a Typ
Colla en-GAG Matrix: Contracti
J. Zaleskas, et al .,
Biomat. 25:1299 (2004)
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40 min
300 minCourtesy Elsevier, Inc., http://www.sciencedirect.com. Used with permission.
40 min
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Non-Seeded: 8 days Cell-Seeded: 8 d
mm
Non-Seeded: 8 days- Cell-Seeded: 8 da- -
10mm
Non-Seeded and Cell-Seeded
Collagen-GAG Scaffolds
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Adult canine articular chondrocytes (passage 3) c
colla en-GAG matrix, reflected in the decrease
100 Mean SE
80 90
e t
e r
70
l D i a
50 r i g i n
40
Adult canine articular chondrocytes (passage 3) con
collagen-GAG matrix, reflected in the decrease in
H
h
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Human Articular Chondrocytes in MonolIH - Green: -smooth muscle actin; Orange: ty
Chondrocytes
express the gene
Smooth Muscle Actin Immunohistoch
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-Smooth Muscle Actin Immunohistoch
of Human Articular Cartilage
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••Articular chondrocyteArticular chondrocyte
•• OsteoblastOsteoblastOsteoblastOsteoblast
•• Meniscus fibroblast and fibrochoMeniscus fibroblast and fibrocho
•• Intervertebral disc fibroblast andIntervertebral disc fibroblast andfibrochondrocytefibrochondrocyte
•• Ligament fibroblastLigament fibroblast
•• Tendon fibroblastTendon fibroblast
MUSCULOSKELETAL CELLS THAT CA
a-SMOOTH MUSCLE ACTIN AND CAN C
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Musculoskeletal Connective Tissue Musculoskeletal Connective Tissue
•• HealingHealing Closure of woundsClosure of woundsskin wounds and bonskin wounds and bon
•• Disease processesDisease processes Contracture (DupuytrContracture (Dupuytr
••
Tissue formationTissue formation Modeling of ECM arcModeling of ECM arcand remodelingand remodeling ((e.g.,e.g., crimp in ligamencrimp in ligamen
POSSIBLE ROLES FOR -SMOOTH
ACTIN-ENABLED CONTRACTION
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•• Control VolumeControl Volume
•• Unit Cell ProcessesUnit Cell Processes
••
•• Tissue Formation and RemodelinTissue Formation and Remodelin
•• oun ea ngoun ea ng n von vo
CONCEPTS FOR UNDERSTANDIN
BIOMATERIALS-TISSUE INTERA
TYPES OF TISSUES
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YesYes
Connective TissuesConnective Tissues
•• BoneBone √√
•• Articular Cartilage,Articular Cartilage,Ligament, IntervertebralLigament, Intervertebral
Epithelia (e.g., epidermis)Epithelia (e.g., epidermis) √√
MuscleMuscle
TYPES OF TISSUESWhich Tissues Can Regenerate Spon
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ee a r xa r x
ConnectiveConnectiveTissueTissue
EpitheliaEpithelia
usc eusc e
BIOMATERIALS-TISSUE
INTERACTIONS
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SolubleSolubleMechanicalMechanical
AALoading (Strain)Loading (Strain)
Cell + Matrix Product + So
(Regulator)
UNIT CELL PROCESSES
Concept of a “Control Volume” arou
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ConnectiveConnective AdhesionAdhesion
EpitheliaEpithelia
MuscleMuscle
ProteinProtein
CollagenCollagen
erveerve
BIOMATERIALS-TISSUE
INTERACTIONS
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ConnectiveConnective
TissueTissue AdhesionAdhesion
EpitheliaEpithelia
MuscleMuscleCollagenCollagen
BiomaterialBiomaterial
erveerveI t iI t i
BIOMATERIALS-TISSUE
INTERACTIONS
Chinese hamster ovary cell migration in a wound
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Chinese hamster ovary cell migration in a wound
C. W
2:21K.A
Cell
CHO cellsexpress the
α5 β 1 but not
α4 β 1 integrin
Photos removed due to copyright restrictions.
Figure 3 in Watters, C. Cell Biol. Ed . 2:210 (2003
Image and links to associated videos athttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC256980/f
Migration of fibroblast-like fibrosarcoma c
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Migration of fibroblast like fibrosarcoma c
3-D collagen lattice
K.Bi
Reduction of migration speed and
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UCPUCP
MitosisMitosisConnectiveConnectiveyn es syn es s
MigrationMigration
ContractionContraction
TissueTissue
EpitheliaEpithelia
MuscleMuscle EndocytosisEndocytosisNerveNerve
“UNIT CELL PROCESSE
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UCPUCP
MitosisMitosis Cell pCell p
S nthesisS nthesis MatriMatriConnectiveConnective
enzymenzym
MigrationMigration TransTransEpitheliaEpithelia
MuscleMuscle
erveerve
“UNIT CELL PROCESSES
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RegulatorRegulator
Cell + Matrix Product +Cell + Matrix Product + RR
UCPUCP
MitosisMitosis
SynthesisSynthesisConnectiveConnective
TissueTissue
CC
(G(G
C iC iEpitheliaEpithelia
“UNIT CELL PROCESSE
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•• Cytokines/Growth FactorsCytokines/Growth Factors
––http://themedicalbiochemistrypage.ohttp://themedicalbiochemistrypage.o
factors.htmlfactors.html–– (previously:(previously:
http://web.indstate.edu/thcme/mwkihttp://web.indstate.edu/thcme/mwki
REGULATORS
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RegulatorRegulator Mechanical Force (Strain)Mechanical Force (Strain)
Cell + Matrix Product + RCell + Matrix Product + R
UCPUCP
MitosisMitosis
SynthesisSynthesisConnectiveConnective
TissueTissue
AdhesionAdhesionCC
(G(G
MigrationMigrationEpitheliaEpithelia C llC ll
“UNIT CELL PROCESSES
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RegulatorRegulator Mechanical Force (Strain)Mechanical Force (Strain)
Cell + Matrix Product + RCell + Matrix Product + R
UCPUCP
MitosisMitosis
SynthesisSynthesisConnectiveConnective
TissueTissue
AdhesionAdhesion
MigrationMigrationEpitheliaEpithelia C llC ll
“UNIT CELL PROCESSES
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RegulatorRegulator (TGF(TGF-- 1)1)
Cell + Matrix Product + Cell + Matrix Product + MitosisMitosis
SynthesisSynthesisConnectiveConnective
TissueTissue
AdhesionAdhesion
ProteinProtein
CC
((
Matrix strainMatrix strain
(contracture/(contracture/
shrinka eshrinka ep e ap e a CollagenCollagen
“UNIT CELL PROCESSES
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TGFTGF-- 11
ContractionContractionFibroblast + Collagen ContractFibroblast + Collagen Contract
“UNIT CELL PROCESSES
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•• Control VolumeControl Volume
•• Unit Cell ProcessesUnit Cell Processes
••
•• Tissue Formation and RemodelinTissue Formation and Remodelin
•• oun ea ngoun ea ng n von vo
CONCEPTS FOR UNDERSTAND
BIOMATERIALS TISSUE INTERA-
+FGF 2
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TISSUE FO
IN V
Canine chondrocytes grown in
a type II collagen-GAG
scaffold for 2 weeks.
(Safranin O stain for GAGs)
+FGF-2
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•• Control VolumeControl Volume
•• Unit Cell ProcessesUnit Cell Processes
••
•• Tissue Formation and RemodelinTissue Formation and Remodelin
•• oun ea ngoun ea ng n von vo
CONCEPTS FOR UNDERSTAND
BIOMATERIALS-TISSUE INTERA
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InjuryInjury4 T4 T
CC
(Vascularized tissue)(Vascularized tissue)
eparat veeparat veProcessProcess
Regeneration*Regeneration* Repair (SRepair (S
WOUND HEALING
Roots of Tissue Engineering
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Surgical ImplantationSurgical Implantation
Vascular ResponseVascular ResponseClottingClotting
PhagocytosisPhagocytosis
NeovascularizationNeovascularization
AcuteAcute
InflammationInflammation GranGran
TT
Tissue of Labile and Stable CellsTissue of Labile and Stable Cells Tissue of PermaTissue of PermaImplant MovementImplant Movement
rameworramewor rameworramewor carr ncarr n
RESPONSE TO IMPLANTS
WOUND HEALING
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MIT OpenCourseWarehttp://ocw.mit.edu
20.441J / 2.79J / 3.96J / HST.522J Biomaterials-Tissue Interactions
Fall 2009
For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.
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