This paper presents a computer-aided design (CAD) of 3D porous tissue scaffolds with spatial control of encapsulated biomolecule distributions. A localized control of encapsulated biomolecule distribution over 3D structures is proposed to control release kinetics spatially for tissue engineering and drug release. Imaging techniques are applied to explore distribution of microspheres over porous structures. Using microspheres in this study represents a framework for modeling the distribution characteristics of encapsulated proteins, growth factors, cells, and drugs. A quantification study is then performed to assure microsphere variation over various structures under imaging analysis. The obtained distribution characteristics are mimicked by the developed stochastic modeling study of microsphere distribution over 3D engineered freeform structures. Based on the stochastic approach, 3D porous structures are modeled and designed in CAD. Modeling of microsphere and encapsulating biomaterial distribution in this work helps develop comprehensive modeling of biomolecule release kinetics for further research. A novel multichamber single nozzle solid freeform fabrication technique is utilized to fabricate sample structures. The presented methods are implemented and illustrative examples are presented in this paper.
Issue Section:
Research Papers
1.
Palsson
, B. Q.
, and Bhatia
, S. N.
, 2004, Tissue Engineering
, Prentice-Hall
, Englewood Cliffs, NJ
.2.
Starly
, B.
, Lau
, W.
, Bradbury
, T.
, and Sun
, W.
, 2006, “Internal Architecture Design Methodology for Tissue Replacement Structures
,” Comput.-Aided Des.
0010-4485, 38
(2
), pp. 115
–124
.3.
Boucard
, N.
, Viton
, C.
, Agay
, D.
, Mari
, E.
, Roger
, T.
, Chancerelle
, Y.
, and Domard
, A.
, 2007, “The Use of Physical Hyrogels of Chitosan for Skin Regeneration Following Third-Degree Burns
,” Biomaterials
0142-9612, 28
(24
), pp. 3478
–3488
.4.
Ozbolat
, I. T.
, Marchany
, M.
, Bright
, F. V.
, Cartwright
, A. N.
, Gardella
, J. A.
, Hard
, R.
, Hicks
, W. L.
, and Koc
, B.
, 2009, “Feature Based Bio-Modeling of Micro-Patterned Structures for Tissue Engineering,” J. Comput.-Aided Des. Appl., 6(5), pp. 661–671.5.
Ribeiro
, C.
, Barrias
, C.
, and Barbosa
, M.
, 2004, “Calcium Phosphate-Alginate Microspheres as Enzyme Delivery Matrices
,” Biomaterials
0142-9612, 25
(18
), pp. 4363
–4373
.6.
Pasparakis
, G.
, and Bouropoulos
, N.
, 2006, “Swelling Studies and In Vitro Release of Verapamil From Calcium Alginate and Calcium Alginate–Chitosan Beads
,” Int. J. Pharm.
0378-5173, 323
, pp. 34
–42
.7.
Hashimoto
, T.
, Suzuki
, Y.
, Kakimaru
, M.
, and Suzuki
, K.
, 2004, “Development of Alginate Wound Dressings Linked With Hybrid Peptides Derived From Laminin and Elastin
,” Biomaterials
0142-9612, 25
, pp. 1407
–1414
.8.
Ravi
, N.
, Wan
, K.
, Swindle
, K.
, Hamilton
, P.
, and Duan
, G.
, 2006, “Development of Technique to Compare Mechanical Properties of Reversible Hydrogels With Spherical, Square Columnar and Ocular Geometry
,” Polymer
0032-3861, 47
, pp. 4203
–4209
.9.
Agren
, M.
, 1996, “Four Alginate Dressings in the Treatment of Partial Thickness Wounds: A Comparative Experimental Study
,” Br. J. Plast. Surg.
0007-1226, 49
, pp. 129
–134
.10.
Winter
, G.
, 1962, “Formation of the Scab and the Rate of Epithelialization of Superficial Wounds in the Skin of the Young Domestic Pig
,” Nature (London)
0028-0836, 193
, pp. 293
–294
.11.
Knill
, C.
, Kennedy
, K.
, Mistry
, J.
, Miraftab
, M.
, Smart
, G.
, Groocock
, M.
, and Williams
, H.
, 2004, “Alginate Fibres Modified With Unhydrolysed and Hydrolysed Chitosans for Wound Dressings
,” Polymers
, 55
, pp. 65
–76
.12.
Williams
, D.
, and Zhong
, S.
, 1994, “Biodeterioration/Biodegradation of Polymeric Medical Devices In Situ
,” Int. Biodeter. Biodegrad.
0964-8305, 34
(2
), pp. 95
–130
.13.
Blair
, S.
, Jarvis
, P.
, Salmon
, M.
, and Mccollum
, C.
, 1990, “Clinical Trial of Calcium Alginate Haemostatic Swabs
,” Br. J. Plast. Surg.
0007-1226, 77
, pp. 568
–570
.14.
Zhang
, L.
, Long
, C.
, Pan
, J.
, and Qian
, Y.
, 2006, “A Dissolution-Diffusion Model and Quantitative Analysis of Drug Controlled Release From Biodegradable Polymer Microspheres
,” Can. J. Chem. Eng.
0008-4034, 84
, pp. 558
–566
.15.
Zheng
, Y.
, Watanabe
, M.
, Kuraishi
, T.
, Hattori
, S.
, Kai
, C.
, and Shibuya
, M.
, 2007, “Vegf-Enz7/Plgf Specifically Binding to Vegfr-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization
,” Arterioscler., Thromb., Vasc. Biol.
1079-5642, 27
, pp. 503
–511
.16.
Epstein
, S.
, Fuchs
, S.
, Zhou
, Y.
, Baffour
, R.
, and Kornowski
, R.
, 2001, “Therapeutic Interventions for Enhancing Collateral Development by Administration of Growth Factors: Basic Principles, Early Results and Potential Hazards
,” Cardiovasc. Res.
0008-6363, 49
, pp. 532
–542
.17.
Putney
, S. D.
, and Burke
, P. A.
, 1998, “Improve Protein Therapeutics With Sustained Release Formulations
,” Nat. Biotechnol.
1087-0156, 16
, pp. 153
–157
.18.
Six
, K.
, Verreck
, J.
, Peeters
, M.
, Brewster
, M.
, and Mooter
, G.
, 2004, “Increased Physical Stability and Improved Dissolution Properties of Itraconazole, a Class II Drug, by Solid Dispersions That Combine Fast- and Slow-Dissolving Polymers
,” J. Pharm. Sci.
0022-3549, 93
, pp. 124
–131
.19.
Geer
, D. J.
, Swartz
, D. D.
, and Andreadis
, S. T.
, 2005, “Biomimetic Delivery of Keratinocyte Growth Factor Upon Cellular Demand for Accelerated Wound Healing In Vitro and In Vivo
,” Am. J. Pathol.
0002-9440, 167
(6
), pp. 1575
–1588
.20.
Elamanchili
, P.
, Diwan
, M.
, Cao
, M.
, and Samuel
, J.
, 2004, “Characterization of Poly(D,L-Lactic-co-Glycolic Acid) Based Nanoparticulate System for Enhanced Delivery of Antigens to Dendritic Cells
,” Vaccine
0264-410X, 22
, pp. 2406
–2412
.21.
Shi
, G.
, Rouabhia
, M.
, Wang
, Z.
, Dao
, L.
, and Zhang
, Z.
, 2004, “A Novel Electrically Conductive and Biodegradable Composite Made of Polypyrrole Nanoparticles and Polylactide
,” Biomaterials
0142-9612, 25
, pp. 2477
–2488
.22.
Anderson
, J.
, Rosenholm
, J.
, and Linden
, M.
, 2008, “Mesoporous Silica: An Alternative Diffusion Controlled Drug Delivery System
,” Topics in Multifunctional Biomaterials and Devices
, University of Oulu
, Oulu, Finland
.23.
Gombotz
, W. R.
, and Pettit
, D. K.
, 1995, “Biodegredable Polymer for Protein and Peptite Drug Delivery
,” Bioconjugate Chem.
1043-1802, 6
, pp. 332
–351
.24.
Diaz
, R. V.
, Soriano
, I.
, Delgado
, A.
, Llabrés
, M.
, and Evora
, C.
, 1997, “Effect of Surfactant Agents on the Release of I-Bovine Calcitonin From PLGA Microspheres: In Vitro—In Vivo Study
,” J. Controlled Release
0168-3659, 43
, pp. 59
–64
.25.
Lemoine
, D.
, Wauters
, F.
, Bouchend’homme
, F.
, and Préat
, V.
, 1998, “Preparation and Characterization of Alginate Microspheres Containing a Model Antigen
,” Int. J. Pharm.
0378-5173, 176
, pp. 9
–19
.26.
Mumper
, R. J.
, Hoffman
, P.
, Puolakkainen
, L. S.
, Bouchard
, L. S.
, and Gombotz
, W. R.
, 1994, “Calcium-Alginate Beads for Oral Delivery of Transforming Grpwth Factor-B: Stabilization of Tgf-B by the Addition of Polyacrylic Acid Within Acid Treated Beads
,” J. Controlled Release
0168-3659, 30
, pp. 241
–251
.27.
Murata
, Y.
, Nakata
, K.
, Miyamoto
, E.
, Kawashima
, S.
, and Seo
, S. H.
, 1993, “Influence of Erosion of Calcium-Induced Alginate Legmatrix on the Release of Brilliant Blue
,” J. Controlled Release
0168-3659, 23
, pp. 21
–26
.28.
Cappai
, A.
, Petruzzo
, P.
, Ruiu
, G.
, Congiu
, T.
, Dessy
, E.
, Desata
, W.
, Cruz
, G.
, and Brotzo
, G.
, 1995, “Evaluzation of New Small Barium Alginate Microcapsules
,” Int. J. Artif. Organs
0391-3988, 18
, pp. 95
–102
.29.
Edelman
, E. R.
, Mathiowitz
, E.
, Langer
, R.
, and Klagsbrun
, M.
, 1991, “Controlled and Modulated Release of Basic Fibroplast Growth Factor
,” Biomaterials
0142-9612, 12
, pp. 619
–626
.30.
Perkins
, J.
, Desai
, S.
, Harrison
, B.
, and Sankar
, J.
, 2009, “Understanding Release Kinetics of Calcium Alginate Microcapsules Using Drop on Demand Inkjet Printing
,” ASME International Mechanical Engineering Congress and Exposition
, Florida.31.
Lin
, C.
, and Metters
, A.
, 2006, “Hydrogels in Controlled Release Formulations: Network Design and Mathematical Modeling
,” Adv. Drug Delivery Rev.
0169-409X, 58
, pp. 1379
–1408
.32.
Khalil
, S.
, and Sun
, W.
, 2007, “Biopolymer Deposition for Freeform Fabrication of Hydrogel Tissue Constructs
,” Mater. Sci. Eng., C
0928-4931, 27
(3
), pp. 469
–478
.33.
Sachlos
, E.
, Reis
, N.
, Ainsley
, C.
, Derby
, B.
, and Czernushka
, J. T.
, 2003, “Novel Collagen Scaffolds With Predefined Internal Morphology Made by Solid Freeform Fabrication
,” Biomaterials
0142-9612, 24
, pp. 1487
–1497
.34.
Chang
, R.
, Nam
, J.
, and Sun
, W.
, 2008, “Direct Cell Writing of 3d Micro-Organ for in Vitro Pharmacokinetic Model
,” Tissue Eng.
1076-3279, 14
(2
), pp. 157
–169
.35.
Chang
, R.
, Nam
, J.
, and Sun
, W.
, 2008, “Computer-Aided Design, Modeling, and Freeform Fabrication of 3d Tissue Constructs for Drug Metabolism Studies,” J. Comput.-Aided Des. Appl., 5, pp. 21–29.36.
Ozbolat
, I.
, Khoda
, A.
, and Koc
, B.
, 2009, “Geometric Modeling of Complex Tissue Engineering Scaffolds With Controlled Porosity Distribution
,” Industrial Engineering Research Conference
, Miami, FL.37.
Chimate
, C.
, 2010, “Pressure Assisted Multi-Syringe Single Nozzle Deposition System for Fabrication of Heterogeneous Tissue Scaffolds
,” Ph.D. thesis, University at Buffalo, Buffalo, NY.38.
Robert Mcneel and Associates, 2007, RHINOCEROS 4.0, Seattle, WA.
39.
Minitab Inc., 2010, MINITAB 15, State College.
40.
Pan
, H.
, and Liou
, F.
, 2005, “Numerical Simulation of Metallic Powder Flow in a Coaxial Nozzle for the Laser Aided Deposition Process
,” J. Mater. Process. Technol.
0924-0136, 168
, pp. 230
–244
.41.
Aludaat
, K.
, and Alodat
, M.
, 2008, “A Note on Approximating the Normal Distribution Function
,” Appl. Math. Sci.
0066-5452, 2
(9
), pp. 425
–429
.42.
Khalil
, S.
, 2005, “Deposition and Structural Formation of 3D Alginate Tissue Scaffold
,” Ph.D. thesis, Drexel University, Philadelphia, PA.43.
Ozbolat
, I.
, Khoda
, A.
, and Koc
, B.
, 2010, “Toolpath Optimization in Solid Freeform Modeling and Fabrication for Tissue Engineering
,” Industrial Engineering Research Conference
, Cancun, Mexico.Copyright © 2010
by American Society of Mechanical Engineers
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