Tissue adhesion Oxidized dextran (DextOx) is used to enhance PGSA’s surface chemical properties....

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Tissue adhesion Oxidized dextran (DextOx) is used to enhance PGSA’s surface chemical properties. As in other oxidized polysaccharides, the aldehyde groups in DextOx react with protein amine and forms imine bond. The biocompatibility and biodegradability of DextOx makes it relevant for tissue interfacing. Motivation Motivation There is significant medical need to develop a tough, biodegradable adhesive that can attach strongly to tissue, yet still accommodate the mechanical deformations present. This material would be useful as replacement or support for sutures and/or patches to aid in hemostasis. The current medical adhesives are limited in applications due to insufficient mechanical properties, difficulty in application and/or non-tailored degradation rates with the healing time of the tissue. proach - Inspirations from Nature proach - Inspirations from Nature Bioadhesive Performance Bioadhesive Performance Poly(glycerol-sebacate-acrylate) (PGSA) Elastomer 1. Fabricate silicon template by photolithography and reactive-ion etching Gecko adhesion The footpad of many insects and lizards are decorated with fibrillar structures called setae. Previous work has demonstrated that the mechanisms of adhesion include the coupling of wan der Waals attraction and pattern geometry in tuning interfacial strength. Biocompatibility NIRT: Biomimetic Nanostructured Medical Adhesives CBET 0609182 Edwin P. Chan, Alborz Madhavi, Lino Ferreira, Jason Nichol, Jeffrey Karp Robert Langer (PI), Joseph Vacanti(co-PI), David Carter (co-PI), Jeffrey Borenstein (co-PI) Tuning Mechanical Properties The Young’s modulus and toughness of the material can be easily tuned by the incorporation of the acrylate side groups that provides the functionality for forming a crosslinked network. Milestones Developed a biodegradable, biocompatible adhesive with tailored interactions with tissue • Created a general methodology to nanopattern and surface modify the bioadhesive • Examined the degradation characteristics of the material • Performed adhesion testing of the bioadhesive Adhesion Testing To simulate the interaction of the bioadhesive to tissue, we measured the adhesion of the materials in aquesous conditions. Additionally, to mimic the mechanical stresses experienced by the adhesive, we used a shear-based adhesion tests to replicate the biological conditions. Bioadhesive Fabrication Bioadhesive Fabrication Nanopatterned PGSA Elastomer • Polycondensation of PGS • Acrylation of PGS 2. Nanomold the PGSA prepolymer with template and photocure prepolymer 3. Remove PGSA elastomer from template to generate the nanopatterned PGSA adhesive 4. Spin-coat DextOx onto PGSA elastomer to generate the final tissue adhesive A Gecko-inspired Bioadhesive Here, we combine the design strategies of the gecko (that provides enhanced dry adhesion by surface patterns) and incorporate covalent surface chemistry to develop a new type of solid-state bioadhesive with tailored interactions with tissue. In-vitro testing Nanopatterns to enhance mechanical compliance with tissue Aldehyde chemistry for tissue adhesion Controlling adhesion w/ nanopatterns Controlling adhesion w/ nanopattern & surface chemistry (DXTA) Biodegradation response Fibroblast spreading Confluent cell layer Cell adhesion & proliferation Bioadhesive Porcine intestine tissue 0.8 acrylation PGSA 0.3 acrylation PGSA w/ 5% PEG 0.3 acrylation PGSA

Transcript of Tissue adhesion Oxidized dextran (DextOx) is used to enhance PGSA’s surface chemical properties....

Page 1: Tissue adhesion Oxidized dextran (DextOx) is used to enhance PGSA’s surface chemical properties. As in other oxidized polysaccharides, the aldehyde groups.

Tissue adhesionOxidized dextran (DextOx) is used to enhance PGSA’s surface chemical properties. As in other oxidized polysaccharides, the aldehyde groups in DextOx react with protein amine and forms imine bond. The biocompatibility and biodegradability of DextOx makes it relevant for tissue interfacing.

MotivationMotivationThere is significant medical need to develop a tough, biodegradable adhesive that can attach strongly to tissue, yet still accommodate the mechanical deformations present. This material would be useful as replacement or support for sutures and/or patches to aid in hemostasis. The current medical adhesives are limited in applications due to insufficient mechanical properties, difficulty in application and/or non-tailored degradation rates with the healing time of the tissue.

Approach - Inspirations from NatureApproach - Inspirations from Nature

Bioadhesive PerformanceBioadhesive Performance

Poly(glycerol-sebacate-acrylate) (PGSA) Elastomer

1. Fabricate silicon template by photolithography and reactive-ion etching

Gecko adhesionThe footpad of many insects and lizards are decorated with fibrillar structures called setae. Previous work has demonstrated that the mechanisms of adhesion include the coupling of wan der Waals attraction and pattern geometry in tuning interfacial strength.

Biocompatibility

NIRT: Biomimetic Nanostructured Medical Adhesives CBET 0609182

Edwin P. Chan, Alborz Madhavi, Lino Ferreira, Jason Nichol, Jeffrey KarpRobert Langer (PI), Joseph Vacanti(co-PI), David Carter (co-PI), Jeffrey Borenstein (co-PI)

Tuning Mechanical PropertiesThe Young’s modulus and toughness of the material can be easily tuned by the incorporation of the acrylate side groups that provides the functionality for forming a crosslinked network.

Milestones• Developed a biodegradable, biocompatible adhesive with tailored interactions with tissue • Created a general methodology to nanopattern and surface modify the bioadhesive• Examined the degradation characteristics of the material• Performed adhesion testing of the bioadhesive

In-progress• In-vivo testing of bioadhesive in small animal models

Adhesion TestingTo simulate the interaction of the bioadhesive to tissue, we measured the adhesion of the materials in aquesous conditions. Additionally, to mimic the mechanical stresses experienced by the adhesive, we used a shear-based adhesion tests to replicate the biological conditions.

Bioadhesive FabricationBioadhesive Fabrication

NanopatternedPGSA Elastomer

• Polycondensation of PGS

• Acrylation of PGS

2. Nanomold the PGSA prepolymer with template and photocure prepolymer

3. Remove PGSA elastomer from template to generate the nanopatterned PGSA adhesive

4. Spin-coat DextOx onto PGSA elastomer to generate the final tissue adhesive

A Gecko-inspired BioadhesiveHere, we combine the design strategies of the gecko (that provides enhanced dry adhesion by surface patterns) and incorporate covalent surface chemistry to develop a new type of solid-state bioadhesive with tailored interactions with tissue.

In-vitro testing

Nanopatterns to enhance mechanical compliance with tissue

Aldehyde chemistry for tissue adhesion

Controlling adhesion w/ nanopatterns

Controlling adhesion w/nanopattern & surface chemistry (DXTA)

Biodegradation responseFibroblast spreading

Confluent cell layer

Cell adhesion & proliferation

Bioadhesive

Porcine intestine tissue

0.8 acrylation PGSA

0.3 acrylation PGSA w/ 5% PEG

0.3 acrylation PGSA