BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Lecture 7: Hydrogel Biomaterials: Structure and Physical Chemistry Last Day: programmed/regulated/multifactor controlled release for drug delivery and tissue engineering Toda Applications of hydrogels in bioengineering Covalent hydrogels structure and chemistry of biomedical gels Thermodynamics of hydrogel swelling Readin N.A. Peppas et aL., "Physicochemical foundations and structural design of hydrogels in medicine and biology, Annu. Rev. Biomed Eng, 2, 9-29(2000) Supplementary Reading: P.J. Flory, Principles of Polymer Chemistry, Cornell University Press, Ithaca, pp 464 469, pp. 576-581 Statistical thermodynamics of networks and network swelling) Applications of hydrogels in bioengineering Hydrogels: insoluble network of polymer chains that swell in aqueous solutions Gels can be classified by the type of crosslinker Covalent covalent junctions Physical non-covalent junctions Lecture 7-Hydrogels 1 1of15
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 7: Hydrogel Biomaterials: Structure and Physical Chemistry Last Day: programmed/regulated/multifactor controlled release for drug delivery and tissue engineering Today: Applications of hydrogels in bioengineering Covalent hydrogels structure and chemistry of biomedical gels Thermodynamics of hydrogel swelling Reading: N.A. Peppas et al., ‘Physicochemical foundations and structural design of hydrogels in medicine and biology,’ Annu. Rev. Biomed. Eng., 2, 9-29 (2000). Supplementary Reading: P.J. Flory, ‘Principles of Polymer Chemistry,’ Cornell University Press, Ithaca, pp. 464- 469, pp. 576-581 (Statistical thermodynamics of networks and network swelling) Applications of hydrogels in bioengineering • Hydrogels: insoluble network of polymer chains that swell in aqueous solutions • Gels can be classified by the type of crosslinker:1 • Covalent - covalent junctions • Physical - non-covalent junctions Lecture 7 – Hydrogels 1 1 of 15
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Physical gels: example-Hydrophobic interactions in physical gels Physical gels are formed by noncovalent cross-links Example blocks: Poly(ethylene glycol)(PEG) Hydrophilic B blocks 3} Hydrophobic A blocks Poly(propylene oxide)(PPO) Poly(butylene oxide)(PBO) Key properties of gels for bioengineering applications 1. in situ formability 2. degradability 3. responsⅳ e swelling 4. tissue-like structure/properties In situ formability Gelation of liquid solutions by Irradiation with light Temperature change(e.g. 4.C to 37C) Cross-linking enzymes Presence of divalent salts ON BOARD In situ formation Heat ACrosslinking by enzymes ntroduction of divalent cations(e.g. Ca*, Mg*) Lecture 7-Hydrogels 1 20f15
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Physical gels: example- Hydrophobic water interactions in physical gels Physical gels are formed by noncovalent Example blocks: cross-links Poly(ethylene glycol) (PEG) Hydrophilic B blocks Hydrophobic A blocks Poly(propylene oxide) (PPO) Poly(butylene oxide) (PBO) • Key properties of gels for bioengineering applications: 1. in situ formability 2. degradability 3. responsive swelling 4. tissue-like structure/properties • In situ formability Gelation of liquid solutions by: • Irradiation with light • Temperature change (e.g. 4°C to 37°C) • Cross-linking enzymes • Presence of divalent salts ON BOARD: In situ formation ¥hν ¥Heat ¥Crosslinking by enzymes ¥Introduction of divalent cations (e.g. Ca++, Mg++) Lecture 7 – Hydrogels 1 2 of 15
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Key properties of hydrogels for bioengineering applications: example: rintableggels printing heads provide470°C dispensing Temperature-controlled stage (Irvine lab) ON BOARD gra Gel with degradable cross links or network chains Eliminable/metabolizable Basis of sensors and 'smart materials (to be covered later) Lecture 7-Hydrogels 1 3of15
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Key properties of hydrogels for bioengineering applications: example: ÔprintableÕgels ∆T Chilled/heated (Landers et al. 2002) printing heads provide 4-70°C dispensing Temperature-controlled stage (Irvine lab) • Degradability ON BOARD: Degradability ¥Hydrolysis ¥Enzymatic attack Gel with degradable cross- Eliminible/metabolizable links or network chains Water-soluble fragments • Responsive swelling Temperature-, pH-, and molecule-responsive swelling Basis of sensors and ‘smart’ materials (to be covered later) Lecture 7 – Hydrogels 1 3 of 15
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 ON BOARD esponsive swell ￥ADH ￥△T ￥△c( change in concentration of a molecule Tissue-like structure/properties Form swollen networks similar to collagen, elastin, proteoglycans General areas of application in bioengineering Controlled release ON BOARD Controlled rele Tissue barriers(Hubbell? Prevent thrombosis(vessel blocked by coagulating platelets)and restenosis(re-narrowing of blood vessel after operation) in vessels after vascular injurylangioplastyletc. Prevent tissue-tissue adhesion after an operation Tissue barriers and conformal coatings Adsorbed layer of Blood vessel vessel Photoinitiator solution Two layers of Green laser formed in situ 2=H-c-0(H)c-c=o2 late solutio (An and Hubbell 2000) Lecture 7-Hydrogels 1 40f15
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 7 – Hydrogels 1 4 of 15 ON BOARD: Responsive swelling ¥ ∆pH ¥ ∆T ¥ ∆c (change in concentration of a molecule • Tissue-like structure/properties Form swollen networks similar to collagen, elastin, proteoglycans • General areas of application in bioengineering: • Controlled release ON BOARD: Controlled release • Tissue barriers (Hubbell2,3) Prevent thrombosis (vessel blocked by coagulating platelets) and restenosis (re-narrowing of blood vessel after operation) in vessels after vascular injury/angioplasty/etc. Prevent tissue-tissue adhesion after an operation Tissue barriers and conformal coatings (An and Hubbell 2000) Adsorbed layer of Blood photoinitiator vessel Photoinitiator solution PEG-diacrylate solution Green laser 3) 2) 1) Two layers of hydrogel formed in situ vessel
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 TE scaffolds/cell encapsulation/immunoisolation. 5 Colloidal crystal template Poly(methyl methacrylate) microspheres 1. Perfect connectivity for Filling of the interstices cell migration atrix or wi 2. Improved nutrient nanoparticles Hydrogel 3. No dead volume precursor polymerize Ordered Dissolve porous microspheres 签签 structure Structured porous replica A M. Lenhoff. CuT. Hydrogel @verse opals Optical micrograph/20 um pores Fluorescence micrograph/60 um pores Biosensors( to be covered later) Contact lenses Lecture 7-Hydrogels 1 5of15
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 • TE scaffolds/cell encapsulation/immunoisolation4,5 Poly(methyl methacrylate) microspheres Perfect connectivity for cell migration Improved nutrient transport No Ôdead volumeÕ O.D. Velev and A.M. Lenhoff, Curr. Opin. Coll. Interf. Sci. 5, 56 (2000) Advantages: 1. 2. 3. Hydrogel precursor polymerize Dissolve microspheres Ordered porous structure Hydrogel Ôinverse opalsÕ Optical micrograph/20 µm pores 60 µm Fluorescence micrograph/60 µm pores • Biosensors (to be covered later) • Contact lenses Lecture 7 – Hydrogels 1 5 of 15