Biological Interactions with Materials - Nanobiotechnology

Granulation tissue formation is an essential phase of wound healing that occurs after inflammation.
It involves the growth of new connective tissue and blood vessels, which fills the wound and forms a scaffold for tissue regeneration.
In tissue engineering, biomaterials are often designed to encourage the formation of granulation tissue for faster healing.
The foreign body reaction is the immune system's response to non-degradable implants or foreign materials that the body cannot eliminate.
It involves chronic inflammation and encapsulation of the material to isolate it from the surrounding tissue.
The foreign body reaction can be detrimental in implantable biomaterials because it can prevent proper integration and cause implant failure.
Biomaterials need to be designed to minimize the intensity of the FBR to improve long-term success.
Fibrosis is the excessive accumulation of fibrous connective tissue (mainly collagen) as a part of the wound healing process or chronic inflammation.
It results in the thickening and scarring of the tissue, often leading to dysfunction of the tissue or organ.
Fibrosis is common in many chronic diseases, including liver cirrhosis, lung fibrosis, and kidney fibrosis.
In the context of biomaterials, fibrosis can prevent proper tissue integration with the implant, leading to device failure.
Blood-biomaterial interactions are critical for the performance and biocompatibility of medical devices that come into contact with blood, such as stents, catheters, and heart valves.
These interactions determine how the body reacts to the material, influencing inflammation, immune responses, clot formation, and the long-term success of the implant.

Key Phases of Blood-Biomaterial Interactions
Protein adsorption
Platelet adhesion & activation
Coagulation cascade
Complement system activation
Leukocyte activation

1. Presented By
Sijo A
Ph.D. Research Scholar (Microbiology)
School of Biosciences, MACFAST College
Tiruvalla, Kerala, India
BIOLOGICAL INTERACTIONS WITH MATERIALS

2. •Granulationtissueformationisanessentialphaseofwoundhealingthat
occursafterinflammation.
•Itinvolvesthegrowthofnewconnectivetissueandbloodvessels,
whichfillsthewoundandformsascaffoldfortissueregeneration.
•Intissueengineering,biomaterialsareoftendesignedto
encouragetheformationofgranulationtissueforfasterhealing.
GRANULATION TISSUE FORMATION
•Collagen-basedscaffoldsarecommonlyusedinwoundcaretopromotegranulationandtissuerepair
Key Features:
1.Angiogenesis:Newbloodvesselsareformed,providingoxygenandnutrientstosupporttissuerepair.
2.FibroblastProliferation:Fibroblastsareactivatedtoproducecollagen,whichgivesstructuralsupporttothenewtissue.
3.ExtracellularMatrix(ECM)Deposition:Amatrixcomposedmainlyofcollagenandfibronectinislaiddowntosupportcell
growthandtissueremodeling.
4.Epithelialization:Themigrationofepithelialcellsacrossthewoundsurfacetorestoretheskinbarrier.

3. •Theforeignbodyreactionistheimmunesystem'sresponsetonon-degradableimplantsorforeignmaterials
thatthebodycannoteliminate.
•Itinvolveschronicinflammationandencapsulationofthematerialtoisolateitfromthesurroundingtissue.
•Theforeignbodyreactioncanbedetrimentalinimplantablebiomaterialsbecauseitcanpreventproper
integrationandcauseimplantfailure.
•BiomaterialsneedtobedesignedtominimizetheintensityoftheFBRtoimprovelong-termsuccess.
Foreign Body Reaction (FBR)
Example:
Siliconeimplants:
•Usedinbreastaugmentation,siliconeimplantsareoftenrecognizedasforeignbodies.
•Overtime,aforeignbodyreactioncanoccur,leadingtoencapsulationoftheimplant
byafibrouscapsule,whichmaydistorttheimplantandrequiresurgicalintervention.

4. •Fibrosisistheexcessiveaccumulationoffibrousconnectivetissue(mainlycollagen)asa
partofthewoundhealingprocessorchronicinflammation.
•Itresultsinthethickeningandscarringofthetissue,oftenleadingtodysfunctionofthe
tissueororgan.
•Fibrosisiscommoninmanychronicdiseases,includinglivercirrhosis,lungfibrosis,and
kidneyfibrosis.
•Inthecontextofbiomaterials,fibrosiscanpreventpropertissueintegrationwiththe
implant,leadingtodevicefailure.
Fibrosis
Example
PacemakerLeads:Overtime,fibrosisaroundpacemakerleads
caninterferewiththeelectricalsignals,necessitatinglead
replacement.Reducingfibroticresponseiscriticalforlong-
termpacemakerfunctionality.

5. Blood –Biomaterial Interactions
•Blood-biomaterialinteractionsarecriticalfortheperformanceandbiocompatibilityofmedicaldevicesthat
comeintocontactwithblood,suchasstents,catheters,andheartvalves.
•Theseinteractionsdeterminehowthebodyreactstothematerial,influencinginflammation,immune
responses,clotformation,andthelong-termsuccessoftheimplant.
KeyPhasesofBlood-BiomaterialInteractions
1.Proteinadsorption
2.Plateletadhesion&activation
3.Coagulationcascade
4.Complementsystemactivation
5.Leukocyteactivation

6. Blood –Biomaterial Interactions
KeyPhasesofBlood-BiomaterialInteractions
1.Proteinadsorption
•Whenabiomaterialisintroducedintothebloodstream,bloodproteins(e.g.,fibrinogen,albumin,
immunoglobulins)rapidlyadsorbontoitssurface.
•Thenatureandpatternofproteinadsorptionarecriticalbecausetheseproteins"condition"thebiomaterial
surfaceanddictatehowcellsandplateletsinteractwithit.
•TheVromanEffect:Aphenomenonwheredifferentbloodproteinsadsorbanddesorbfromthebiomaterial
surfacebasedontheirsizeandconcentration.Initially,smallerproteinslikealbuminadsorb,buttheyare
laterreplacedbylargerproteinslikefibrinogenandfibronectin.

7. Blood –Biomaterial Interactions
KeyPhasesofBlood-BiomaterialInteractions
2.Plateletadhesion&activation
•Plateletsareactivatedwhentheyinteractwiththeadsorbedproteinson
thebiomaterialsurface,particularlyfibrinogen.
•Activatedplateletschangeshape,releasesignalingmolecules(e.g.,ADP,
thromboxane),andforma"plateletplug"aspartoftheclottingprocess.
•Biomaterialsthatstronglyactivateplateletsincreasetheriskofthrombosis
(clotformation),whichcanbedangerousinblood-contactingdevices.
•Example:Invasculargraftsorstents,excessiveplateletactivationcanlead
tothrombus(clot)formation,whichcanblockbloodflowandresultin
devicefailureorseverecomplications.

8. Blood –Biomaterial Interactions
KeyPhasesofBlood-BiomaterialInteractions
3.Coagulationcascade
•Thecoagulationcascadeisaseriesofenzymaticreactionstriggeredbyproteinadsorptionandplatelet
activation.
•Itleadstotheformationoffibrin,aproteinthatformsamesh-likestructuretostabilizetheplateletplugand
createabloodclot.
•Therearetwopathwaysthatcanactivatethecoagulationcascade:
1.IntrinsicPathway:Triggeredbycontactwiththebiomaterialsurface.
2.ExtrinsicPathway:Triggeredbytissuedamageduringsurgeryorimplantplacement.

9. Blood –Biomaterial Interactions
KeyPhasesofBlood-BiomaterialInteractions
4. Complement System Activation:
•Thecomplementsystemisapartoftheimmunesystemthatisactivated
bytheinteractionbetweenbiomaterialsandbloodproteins.
•WhenproteinslikeC3bbindtothebiomaterialsurface,itactivatesthe
complementpathway,leadingtoinflammationandrecruitmentof
immunecells(e.g.,neutrophils,macrophages).
•Chroniccomplementactivationcanresultinlong-terminflammation,
whichcanimpairthefunctionalityofthebiomaterial.
•Example:Hemodialysismembranescantriggercomplementactivation,
leadingtoinflammationandadversereactionsinpatientsundergoing
dialysistreatment.

10. Blood –Biomaterial Interactions
KeyPhasesofBlood-BiomaterialInteractions
5. Leukocyte (White blood cell) activation
•Leukocytescanadheretobiomaterialsthroughinteractionswithadsorbedproteinslike
fibrinogenandcomplementcomponents.
•Onceadhered,theybecomeactivatedandreleasepro-inflammatorycytokines,whichcan
leadtotissuedamageandchronicinflammationaroundtheimplant.
•Thepresenceofleukocytesalsopromotestheforeignbodyreaction,especiallyifthe
materialcannotbeeasilydegradedorintegratedbythebody.
•Example:Insomevasculargraftsorartificialheartvalves,leukocyteactivationcontributes
totheformationofafibrouscapsule,impairingthefunctionofthedevice.

11. Outcomes of Blood –Biomaterial Interactions
Thrombosis:
•Formationofabloodclot(thrombus)onthesurfaceofabiomaterial.
•Resultsfromexcessiveplateletactivation,proteinadsorption,andactivationofthecoagulationcascade.
•Prevention:Surfacemodificationslikeheparincoatings(ananticoagulant)ortheuseofhydrophilicmaterialsthatresistprotein
adsorptioncanhelpreducethrombosisrisk.
Inflammation:
•Thebody'simmuneresponsetoforeignmaterials.
•Activationofthecomplementsystemandleukocyteadhesion.
•Prevention:Surfaceengineering,suchasPEGylation(coatingwithpolyethyleneglycol),canreduceproteinadsorptionand
immuneactivation,therebyminimizinginflammation.
FibrousCapsuleFormation:
•Theformationofadenselayeroffibroustissuearoundthebiomaterial,isolatingitfromthesurroundingtissue.
•Cause:Chronicinflammationandforeignbodyreactionsdrivenbyprolongedimmunecellactivation.
•Consequence:Fibrosiscanimpairthefunctionofthebiomaterial,especiallyincasesofimplantslikepacemakersorjoint
prostheses.