Roche C. de Guzman, Ph.D. Assistant Professor Department of Engineering, Hofstra University
http://people.hofstra.edu/Roche_C_deGuzman/
• • • •
Keratin biomaterials for drug delivery
Biomaterials Tissue Engineering and Regenerative Medicine Drug Delivery Medical Devices
hair keratin powder
Poly(ethylene glycol) (PEG)-based materials
Improve sample extraction processes ⋆ Separate KAPs ⋆ Preserve free thiols ⋆ Maintain fibrous structures ⋆ Remove melanin for optical clarity ⋆ Understand the reversible gelation mechanism
bifunctional (diacrylate) PEG chains
linear extension
Peer-Reviewed Publications o o o o o o o o o
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de Guzman RC, Rabbany SY. PEG-immobilized keratin for protein drug sequestration and pH-mediated delivery. Journal of Drug Delivery (2016) 10.1155/2016/7843951. PMID: 26904294 de Guzman RC, Tsuda SM, Ton MN, Zhang X, Esker AR, Van Dyke ME. Binding interactions of keratin-based hair fiber extract to gold, keratin, and BMP-2. PLOS ONE (2015) 10:e0137233. PMID: 26317522 de Guzman RC, Saul JM, Ellenburg MD, Merrill MR, Coan HB, Smith TL, Van Dyke ME. Bone regeneration with BMP-2 delivered from keratose scaffolds. Biomaterials (2013) 34:1644-1656. PMID: 23211447 Richter JR, de Guzman RC, Greengauz-Roberts OK, Van Dyke ME. Structure-property relationships of meta-kerateine biomaterials derived from human hair. Acta Biomaterialia (2012) 8:274-281. PMID: 21911088 de Guzman RC, Merrill MR, Richter JR, Hamzi RI, Greengauz-Roberts OK, Van Dyke ME. Mechanical and biological properties of keratose biomaterials. Biomaterials (2011) 32:8205-8217. PMID: 21835462 Richter JR, de Guzman RC, Van Dyke ME. Mechanisms of hepatocyte attachment to keratin biomaterials. Biomaterials (2011) 32:7555-7561. PMID: 21782237 Saul JM, Ellenburg MD, de Guzman RC, Van Dyke ME. Keratin hydrogels support the sustained release of bioactive ciprofloxacin. Journal of Biomedical Materials Research Part A (2011) 98:544-553. PMID: 21681948 de Guzman RC, Loeb JA, VandeVord PJ. Electrospinning of matrigel to deposit a basal lamina-like nanofiber surface. Journal of Biomaterials Science. Polymer Edition (2010) 21:1081-1101. PMID: 20507710 de Guzman RC, Ereifej ES, Broadrick KM, Rogers RA, VandeVord PJ. Alginate-matrigel microencapsulated Schwann cells for inducible secretion of glial cell line derived neurotrophic factor. Journal of Microencapsulation (2008) 25:487-498. PMID: 19238724 de Guzman RC, VandeVord PJ. Variations in astrocyte and fibroblast response due to biomaterial particulates in vitro. Journal of Biomedical Materials Research Part A (2008) 85:14-24. PMID: 17668862
⋆ How does KTN assemble to form suprastructures? ⋆ What are the roles of KAPs?
⋆ KTN-Au nanoparticle applications ⋆ Ideal release kinetics of growth factors?
crosslink physical mix; covalent link
polymer electrospin
adsorb; covalent link
+ active factors
gel; cast
⋆ pH and salt-mediated drug delivery strategies
BMP-2-to-KTN in PBS
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đ?‘˜đ?‘‘ + đ??´ đ?‘˜đ?‘Ž đ?‘‘đ?‘–đ?‘ đ?‘ đ?‘œđ?‘?đ?‘–đ?‘Žđ?‘Ąđ?‘–đ?‘œđ?‘›: đ?‘…đ?‘Ą = đ?‘…0(đ?‘’ −đ?‘˜đ?‘‘đ?‘Ą )
(non-specific) (non-specific)
1 − đ?‘’ −(đ?‘˜đ?‘Ž đ??´ +đ?‘˜đ?‘‘)đ?‘Ą
KD (M) 10-15 to 10-13 10-11 to 10-9 10-9 to 10-7 10-6 to 10-5 ≼ 10-4
Cells on the substrate
keratin-BMP-2 bioactivity
Concentration (C)
O2
BULK
Biomaterial Constructs
freeze-dry; leach
absorb; covalent link
thick scaffold
BULK
biomaterial functionalization
Position (x)
V = 30 kV d = 7 cm Q = 1 mL/hr [solute] = 4 % ω =500 rpm E = 4.29 kV/cm
Oxygen transport into the microcapsule Fick’s second law of diffusion: �C �2C = χ 2 �t d� χ = diffusivity ideal diameter: 200 to 500 Οm
alginate cell microencapsulation
histology
torsional biomechanics
Propylene Glycol 0 0%
20%
40%
60%
80%
100%
Relative Plasticizer Saturation in PEG
with chitosan for acidic degradation
immobilized in bulk
⋆ Effect of vacuum, and increased pressure and temperature during the film-making process protein absorption and interaction
subcutaneous implantation
degradable region plasticizer
integrin receptorbinding
modification strategies
+ + + --
PEG chains potent growth factors
negativelycharged molecule
electric current control
particle simulation
electrospinning of nanofibers and meshes
⋆ Improve using vibrating jet or electrostatic droplet generator ⋆ Incorporate O2-releasing particles: Na2CO3¡1.5H2O2 and CaO2
crosslinking with PEG
Âť Develop degradable keratin constructs to stimulate recruitment and differentiation of repair stem cells for improved bone tissue regeneration after injury fiber thickness = 100 Âą 5 nm bead content = 11 %
Modified bioglasses to promote biomineralization O O
encapsulated cells secreting therapeutic growth factors
PEG
0.5
⋆ In vivo degradation, biocompatibility, and cell infiltration activities?
release of absorbed proteins
⋆ Divalent cations to alter capsule mechanical properties, induction of precipitates, and promotion of cell functionality?
Sorbitol
⋆ Mathematical modeling ⋆ Controls and simulation ⋆ Interfacing with devices ⋆ Data acquisition ⋆ Problem solving ⋆ Computation of unknowns ⋆ Numerical methods ⋆ Automation of tasks
absorb; covalent link
freeze-dry; leach
⋆ Plasticizers to modulate mechanical properties
MATLAB and Arduino programming
SURFACE
gel
intervertebral disc application
Glycerol
1
⋆ How to keep cells alive and functional?
bone regeneration
branched
1.5
cells on functionalized PEG
bone morphogenetic protein 2 (BMP-2) homodimer
thin scaffold
2
Strength of Association Very very strong Very strong Strong Moderate Weak
⋆ Study the interaction of other growth factors
electrospin
gel; cast
Irgacure 2959 + UV at 254-nm
2.5
with heparin for growth factor sequestration
physisorption of BMP-2 ⋆ Enhance early stages of fracture healing
Active factors incorporation On SURFACE • Physisorption • Chemisorption • Covalent bonding In BULK • Physical association • Absorption • Covalent bonding • Ionic interaction • Bioaffinity
crosslink
Langmuir adsorption isotherm: A (analyte) + B (ligand) ⇌ AB
Specific Molecular Interaction biotin-to-avidin/streptavidin antigen-to-antibody integrin-to-ECM
Biomaterial technologies covalent link
⋆ Incorporation of basic growth factors ⋆ Crosslinking of cell-binding peptides and hydrophobic chains ⋆ Protein adsorption
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in vivo testing
monomeric biomaterial
binding to gold
4-arm PEG
photopolymerization
Desired PEG modifications ⋆ Allow for increased protein adsorption and cell-attachment Chemical APS + TEMED ⋆ Degradability 3.5 ⋆ Electrical charge and binding to drugs 3 ⋆ Flexibility and strength Compressive Modulus = Ec (MPa)
Research Interests
⋆ Synthesize basal lamina nanofibers for peripheral nerve tissue engineering ⋆ Increase yield dorsal root ganglion explant on: smooth electrospun nanorough surface
sintering > Tg then annealing ⋆ Algorithms for Si, P, Na, Ca, and O compounds content and bioactivities at processing conditions ⋆ Different forms: granules, beads, flat substrates, porous scaffolds
O
bioglass in vitro degradation
O
Si O Si
O
Si O O O Si
Ca
O Si O Ca
O Ca
Si O O O Si
Ca
O Na
Na O
O Si
O
O
O
O O P
O
P O
⋆ Control cell and tissue O O O O O P O behavior by release of P Na O O O different ions? 45S5 Bioglass O O ⋆ Addition of metal ions silicon network connectivity (NCSi) = 2.12
Âť Develop new bioglass technology products including induction of hydroxyapatite nucleation in polymer, ceramic, and composite biomaterial scaffolds
O
Acknowledgements • Engineering: Bioengineering Materials Lab (BML), Sina Rabbany and his group, Kevin Craig, Sleiman Ghorayeb, Alex Pesch, Jacqueline Scarola, Lori Castoria, Daniel Foyt, Jennifer Miller, Ariel Golshan, Miguel Hutchinson, Tyler Lavertu, and Horacio Reyna • Biology: Jenesis Curtis, Vasilios Lianos, Emily Diaz, Carol St. Angelo, Nancy Radecker, Reid Wasserman, and Grzegorz Polak • Physics: Jessica Magarinos • Fine Arts, Design, Art History: Paul Chaleff and Bethany Dill • High School: Nathaniel Vaduthala, Daniyal Jamal, and Bradley Sheen