It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100–1000 μm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2–20 μm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds.

References

References
1.
Elvitigala
,
T. R.
,
Polpitiya
,
A. D.
,
Wang
,
W.
,
Stöckel
,
J.
,
Khandelwal
,
A.
,
Quatrano
,
R. S.
,
Pakrasi
,
H.
, and
Ghosh
,
B. K.
, 2010, “
High-Throughput Biological Data Analysis: A Step Towards Understanding Cellular Regulation
,”
IEEE Control Syst. Mag.
,
30
(
1
), pp.
81
100
.
2.
Hollister
,
S. J.
, 2005, “
Porous Scaffold Design for Tissue Engineering
,”
Nature Mater.
,
4
, pp.
518
590
.
3.
Hollister
,
S. J.
, 2009, “
Scaffold Design and Manufacturing: From Concept to Clinic
,”
Adv. Mater.
,
21
, pp.
3330
3342
.
4.
Hing
,
K. A.
, 2005, “
Bioceramic Bone Graft Substitutes: Influence of Porosity and Chemistry
,”
Int. J. Appl. Ceram. Technol.
,
2
(
3
), pp.
184
199
.
5.
Hing
,
K. A.
,
Annaz
,
B.
,
Saeed
,
S.
,
Revell
,
P. A.
, and
Buckland
,
T.
, 2005, “
Microporosity Enhances Bioactivity of Synthetic Bone Graft Substitutes
,”
J. Mater. Sci.: Mater. Med.
,
16
, pp.
467
475
.
6.
Lan Levengood
,
S. K.
,
Polak
,
S. J.
,
Wheeler
,
M. B.
,
Maki
,
A. J.
,
Clark
,
S. G.
,
Jamison
,
R. D.
, and
Wagoner Johnson
,
A. J.
, 2010, “
Multiscale Osteointegration as a New Paradigm for the Design of Calcium Phosphate Scaffolds for Bone Regeneration
,”
Biomaterials
,
31
, pp.
3552
3563
.
7.
Polak
,
S. J.
,
Lan Levengood
,
S. K.
,
Wheeler
,
M. B.
,
Maki
,
A. J.
,
Clark
,
S. G.
, and
Wagoner Johnson
,
A. J.
, 2010, “
Analysis of the Roles of Microporosity and BMP-2 on Multiple Measures of Bone Regeneration and Healing in Calcium Phosphate Scaffolds
,”
Acta Biomater.
,
7
(
4
), pp.
1760
1771
.
8.
Stevens
,
M. M.
, 2008. “
Biomaterials for Bone Tissue Engineering
,”
Mater. Today
,
11
(
5
), pp.
18
25
.
9.
Khoda
,
A.
,
Ozbolat
,
I. T.
, and
Koc
,
B.
, 2011, “
Engineered Tissue Scaffolds With Variational Porous Architecture
,”
J. Biomech. Eng.
,
133
, p.
011001
.
10.
An
,
Y. H.
,
Woolf
,
S. K.
, and
Friedman
,
R. J.
, 2000, “
Pre-Clinical in Vivo Evaluation of Orthopaedic Bioabsorbable Devices
,”
Biomaterials
,
21
, pp.
2635
2652
.
11.
Griffith
,
L. G.
, 2002, “
Emerging Design Principles in Biomaterials and Scaffolds for Tissue Engineering
,”
Ann. N. Y. Acad. Sci.
,
961
, pp.
83
95
.
12.
Wagoner Johnson
,
A. J.
, and
Herschler
,
B. A.
, 2011, “
A Review of the Mechanical Behavior of CaP and CaP/Polymer Composites for Applications in Bone Replacement and Repair
,”
Acta Biomater.
,
7
, pp.
16
30
.
13.
Michna
,
S.
,
Wu
,
W.
, and
Lewis
,
J. A.
, 2005, “
Concentrated Hydroxyapatite Inks for Direct-Write Assembly of 3-D Periodic Scaffolds
,”
Biomaterials
,
26
, pp.
5632
5639
.
14.
Simon
,
J. L.
,
Michna
,
S.
,
Lewis
,
J. A.
,
Rekow
,
E. D.
,
Thompson
,
V. P.
,
Smay
,
J. E.
,
Yampolsky
,
A.
,
Parson
,
J. R.
, and
Ricci
,
J. L.
, 2007, “
In Vivo Bone Response to 3D Periodic Hydroxyapatite Scaffolds Assembled by Direct Ink Writing
,”
J. Biomed. Mater. Res. Part A
,
83
(
3
), pp.
747
758
.
15.
Chu
,
T.-M.
,
Halloran
,
J.
,
Hollister
,
S.
, and
Feinberg
,
S.
, 2001, “
Hydroxyapatite Implants With Designed Internal Architecture
,”
J. Mater. Sci.: Mater. Med.
,
12
(
6
), pp.
471
478
.
16.
Franco
,
J.
,
Hunger
,
P.
,
Launey
,
M.
,
Tomsia
,
A.
, and
Saiz
,
E.
, 2010, “
Direct Write Assembly of Calcium Phosphate Scaffolds Using a Water-Based Hydrogel
,”
Acta Biomater.
,
6
, pp.
218
228
.
17.
Cesarano
,
J.
, III
,
Segalman
,
R.
, and
Calvert
,
P.
, 1998, “
Robocasting Provides Moldless Fabrication From Slurry Deposition
,”
Ceram. Ind.
,
148
(
4
), pp.
94
102
.
18.
Bristow
,
D.
, and
Alleyne
,
A.
, 2006, “
A High Precision Motion Control System With Application to Microscale Robotic Deposition
,”
IEEE Trans. Control Syst. Technol.
,
16
(
6
), pp.
1008
1020
.
19.
Woodard
,
J. R.
,
Hilldore
,
A. J.
,
Lan
,
S. K.
,
Park
,
C.
,
Morgan
,
A. W.
,
Eurell
,
J. A. C.
,
Clark
,
S. G.
,
Wheeler
,
M. B.
,
Jamison
,
R. D.
, and
Wagoner Johnson
,
A. J.
, 2007, “
The Mechanical Properties and Osteoconductivity of Hydroxyapatite Bone Scaffolds With Multi-Scale Porosity
,”
Biomaterials
,
28
(
1
), pp.
45
54
.
20.
Cordell
,
J. M.
,
Vogl
,
M. L.
, and
Wagoner Johnson
,
A. J.
, 2009, “
The Influence of Micropore Size on the Mechanical Properties of Bulk Hydroxyapatite and Hydroxyapatite Scaffolds
,”
J. Mech. Behav. Biomed. Mater.
,
2
, pp.
560
570
.
21.
Cooper
,
K.
, 2001,
Rapid Prototyping Technology: Selection and Application
,
Marcel Dekker
,
New York
.
22.
Smay
,
J. E.
,
Cesarano
,
J.
, III
, and
Lewis
,
J. A.
, 2002, “
Colloidal Inks for Directed Assembly of 3-D Periodic Structures
,”
Langmuir
,
18
(
14
), pp.
5429
5437
.
23.
Hoelzle
,
D. J.
,
Alleyne
,
A. G.
, and
Wagoner Johnson
,
A. J.
, 2008, “
Iterative Learning Control for Robotic Deposition Using Machine Vision
,”
Proceedings of the IEEE American Control Conference
, pp.
4541
4557
.
24.
Hoelzle
,
D. J.
,
Alleyne
,
A. G.
, and
Wagoner Johnson
,
A. J.
, 2011, “
Basis Task Approach to Iterative Learning Control With Applications to Micro-Robotic Deposition
,”
IEEE Trans. Control Syst. Technol.
,
19
(
5
), pp.
1138
1148
.
25.
Hoelzle
,
D. J.
,
Alleyne
,
A. G.
, and
Wagoner Johnson
,
A. J.
, 2008, “
Micro-Robotic Deposition Guidelines by a Design of Experiments Approach to Maximize Reliability for the Bone Scaffold Application
,”
Acta Biomater.
,
4
, pp.
897
912
.
26.
Liu
,
L.
,
Xiong
,
Z.
,
Yan
,
Y.
,
Zhang
,
R.
,
Wang
,
X.
, and
Jin
,
L.
, 2008, “
Multinozzle Low-Temperature Deposition System for Construction of Gradient Tissue Engineering Scaffolds
,”
J. Biomed. Mater. Res., Part B: Appl. Biomater.
,
88B
(
1
), pp.
254
263
.
27.
Ross
,
M. H.
, and
Pawlina
,
W.
, 1995,
Histology: A Text and Atlas
,
Lippincott Williams & Wilkins
,
New York
.
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