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Combining Multi-scale 3D Printing Technologies To Engineer Reinforced Hydrogel-ceramic Interfaces

Paweena Diloksumpan, M. de Ruijter, M. Castilho, U. Gbureck, T. Vermonden, P. R. van Weeren, J. Malda, R. Levato
Published 2020 · Materials Science, Medicine

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Multi-material 3D printing technologies that resolve features at different lengths down to the microscale open new avenues for regenerative medicine, particularly in the engineering of tissue interfaces. Herein, extrusion printing of a bone-biomimetic ceramic ink and melt electrowriting (MEW) of spatially organized polymeric microfibres are integrated for the biofabrication of an osteochondral plug, with a mechanically reinforced bone-to-cartilage interface. A printable physiological temperature-setting bioceramic, based on α-tricalcium phosphate, nanohydroxyapatite and a custom-synthesized biodegradable and crosslinkable poloxamer, was developed as bone support. The mild setting reaction of the bone ink enabled us to print directly within melt electrowritten polycaprolactone meshes, preserving their micro-architecture. Ceramic-integrated MEW meshes protruded into the cartilage region of the composite plug, and were embedded with mechanically soft gelatin-based hydrogels, laden with articular cartilage chondroprogenitor cells. Such interlocking design enhanced the hydrogel-to-ceramic adhesion strength >6.5-fold, compared with non-interlocking fibre architectures, enabling structural stability during handling and surgical implantation in osteochondral defects ex vivo. Furthermore, the MEW meshes endowed the chondral compartment with compressive properties approaching those of native cartilage (20-fold reinforcement versus pristine hydrogel). The osteal and chondral compartment supported osteogenesis and cartilage matrix deposition in vitro, and the neo-synthesized cartilage matrix further contributed to the mechanical reinforcement at the ceramic-hydrogel interface. This multi-material, multi-scale 3D printing approach provides a promising strategy for engineering advanced composite constructs for the regeneration of musculoskeletal and connective tissue interfaces.
This paper references
CornelissenMandBerghmansH2000 Structural and rheological properties ofmethacrylamidemodified gelatin hydrogelsBiomacromolecules
A IVanDenBulcke (2000)
Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration
V. Mouser (2017)
J and HutmacherDW2014Multiphasic construct studied in anectopic osteochondral defectmodel
JE Jeon (2014)
andCorrie SR2016 Nanoparticle-basedmedicines: a reviewof FDA-approved materials and clinical trials to datePharm.Res
BoboD (2016)
PD andGroll J 2015Additivemanufacturing of scaffolds with sub-micron filaments viamelt electrospinningwritingBiofabrication
HochleitnerG (2015)
Rencsok EMandKellyD J 2016A comparison of different bioinks for 3Dbioprinting of fibrocartilage and hyaline cartilageBiofabrication
AC Daly (2016)
Ultra-tough injectable cytocompatible hydrogel for 3D cell culture and cartilage repair.
Yanran Zhao (2018)
Bioactive Stratified Polymer Ceramic-Hydrogel Scaffold for Integrative Osteochondral Repair
J. Jiang (2010)
Pluronic F127 as a cell encapsulation material: utilization of membrane-stabilizing agents.
Sarwat F. Khattak (2005)
J and Mateos-TimonedaMA2014 Biofabrication of tissue constructs by 3Dbioprinting of cell-ladenmicrocarriers Biofabrication
R Levato (2014)
Nanoscale hydroxyapatite particles for bone tissue engineering.
Hongjian Zhou (2011)
Fabrication of porous scaffolds by three‐dimensional plotting of a pasty calcium phosphate bone cement under mild conditions
A. Lode (2014)
Hydrogel-based reinforcement of 3Dbioprinted constructs Biofabrication
F PWMelchels (2016)
Novel multicomponent organicinorganic WPI/gelatin/CaP hydrogel composites for bone tissue engineering
M Dziadek (2019)
Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.
Y. Seol (2015)
Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs.
Khoon S. Lim (2018)
Comparative characterization of the hydrogel added PLA/β-TCP scaffolds produced by 3D bioprinting
M. Aydoğdu (2019)
Solute transport at the interface of cartilage and subchondral bone plate: Effect of micro-architecture.
B. Pouran (2017)
Porous titanium bases for osteochondral tissue engineering.
Adam B. Nover (2015)
The role of alkaline phosphatase in mineralization
E. Golub (2007)
2013Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage
SchuurmanW (2013)
Bioprinting of mineralized constructs utilizing multichannel plotting of a self-setting calcium phosphate cement and a cell-laden bioink.
T. Ahlfeld (2018)
Buoyancy-Driven Gradients for Biomaterial Fabrication and Tissue Engineering.
Chunching Li (2019)
Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs.
W. Schuurman (2013)
Review of potential health risks associated with nanoscopic calcium phosphate.
Matthias Epple (2018)
Tough Bonding of Hydrogels to Diverse Nonporous Surfaces
Hyunwoo Yuk (2016)
Self-Setting Calcium Orthophosphate Formulations
S. Dorozhkin (2013)
Osteochondral tissue formation through adipose-derived stromal cell differentiation on biomimetic polycaprolactone nanofibrous scaffolds with graded insulin and Beta-glycerophosphate concentrations.
C. Erisken (2011)
YuWT,Klein RW,NapolitanoAP, AteshianGA andHungCT 2015Porous titaniumbases for osteochondral tissue
AB Nover (2015)
Chondrocyte redifferentiation and construct mechanical property development in single-component photocrosslinkable hydrogels.
Peter A. Levett (2014)
Simultaneousmicropatterning offibrousmeshes and bioinks for the fabrication of living tissue constructsAdvHealthcMater
deRuijterM (2019)
andBoesze-Battaglia K 2007The role of alkaline phosphatase
EE Golub (2007)
andAza SD2011α-Tricalciumphosphate: synthesis, properties and biomedical applicationsActa Biomater
RG Carrodeguas (2011)
Biofabricated soft network composites for cartilage tissue engineering.
O. Baş (2017)
2016Three-dimensional bioprinting of multilayered constructs containing humanmesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee jointBiofabrication
JH Shim (2016)
BaleaniM andPerssonC 2017 Elastic properties and strain - to - crack - initiation of calciumphosphate bone cements : Revelations of a high - resolutionmeasurement technique
BlokzijlMM RibeiroA
andZhang LG2015 Integrating biologically inspired nanomaterials and table-top stereolithography for 3Dprinted biomimetic osteochondral scaffoldsNanoscale
J CastroN (2015)
Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed microfibre scaffolds
M. Castilho (2018)
The effect of devitalized trabecular bone on the formation of osteochondral tissue-engineered constructs.
E. Lima (2008)
Micro-mechanical properties of the tendon-to-bone attachment.
A. C. Deymier (2017)
andMalda J 2017Melt ElectrospinningWriting of Poly-Hydroxymethylglycolide-co-epsilon-Caprolactone- Based Scaffolds for CardiacTissue Engineering, AdvHealthc Mater
CastilhoM (2017)
vanWeeren PR andDhertW J 2012Comparative study of depth-dependent characteristics of equine andhuman osteochondral tissue from themedial and lateral femoral condylesOsteoarthritis Cartilage
J Malda (2012)
Fiji: an open-source platform for biological-image analysis
Johannes E. Schindelin (2012)
Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds.
N. Castro (2015)
KimDHandChoDW2014 Printing three-dimensional tissue analogueswith decellularized extracellularmatrix bioinkNat
F Pati (2014)
2010Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration
J PGleeson (2010)
Elastic properties and strain-to-crack-initiation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique.
Ingrid Ajaxon (2017)
Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing.
G. Hochleitner (2015)
Preclinical Studies for Cartilage Repair
M. Hurtig (2011)
Three-dimensional bioprinting of cell-laden constructs with polycaprolactone protective layers for using various thermoplastic polymers.
B. Kim (2016)
Melt Electrospinning Writing of Poly‐Hydroxymethylglycolide‐co‐&egr;‐Caprolactone‐Based Scaffolds for Cardiac Tissue Engineering
M. Castilho (2017)
Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date
Daniel Bobo (2016)
ParadaGA andZhaoX 2016Tough bonding of hydrogels to diverse non-porous surfacesNat. Mater
YukH (2016)
T andGelinskyM2014 Fabrication of porous scaffolds by three-dimensional plotting of a pasty calciumphosphate bone cement undermild conditions
LodeA (2014)
HenninkWE,VermondenT andMalda J 2017Assessing bioink shape fidelity to aidmaterial development in 3D bioprintingBiofabrication
RibeiroA (2017)
AhnMandChoDW 2016Three-dimensional bioprinting of cell-laden constructs with polycaprolactone protective layers for using various thermoplastic polymersBiofabrication
KimBS (2016)
Hydrogel-based reinforcement of 3D bioprinted constructs.
F. P. Melchels (2016)
Novel multicomponent organic-inorganic WPI/gelatin/CaP hydrogel composites for bone tissue engineering.
Michal Dziadek (2019)
3D plotting of growth factor loaded calcium phosphate cement scaffolds.
A. R. Akkineni (2015)
A biomimetic multi-layered collagen-based scaffold for osteochondral repair.
Tanya J Levingstone (2014)
BirmanV, GeninGM,Thomopoulos S andBarber AH2017Micromechanical properties of the tendon-to-bone attachmentActa Biomater
AC Deymier (2017)
New Visible-Light Photoinitiating System for Improved Print Fidelity in Gelatin-Based Bioinks.
K. S. Lim (2016)
Engineering human cell-based, functionally integrated osteochondral grafts by biological bonding of engineered cartilage tissues to bony scaffolds.
Celeste Scotti (2010)
Development of novel three-dimensional printed scaffolds for osteochondral regeneration.
B. Holmes (2015)
2011Nanoscale hydroxyapatite particles for bone tissue
J ZhouHand Lee (2011)
Bio-resin for high resolution lithographybased biofabrication of complex cell-laden constructs Biofabrication
LimKS (2018)
* Biomimetic Versus Sintered Calcium Phosphates: The In Vitro Behavior of Osteoblasts and Mesenchymal Stem Cells.
Joanna-Maria Sadowska (2017)
VermondenT andMalda J 2014Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel formechanically enhanced cartilage
BoereKW (2014)
TangA,AteshianGA,GuoXE,HungCTandLuHH 2010Bioactive stratifiedpolymer ceramic-hydrogel scaffold for integrative osteochondral repairAnn.Biomed.Eng.382183–96
J Jiang (2010)
The incorporation of a zone of calcified cartilage improves the interfacial shear strength between in vitro-formed cartilage and the underlying substrate.
Jean-Philippe St-Pierre (2012)
Setting Reaction and Hardening of an Apatitic Calcium Phosphate Cement
M. Ginebra (1997)
Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink
Falguni Pati (2014)
Regulatory Challenges for Cartilage Repair Technologies
Kevin B. McGowan (2013)
The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.
R. Levato (2017)
α-Tricalcium phosphate: synthesis, properties and biomedical applications.
R. G. Carrodeguas (2011)
Zenobi-WongM, GawlittaD andMalda J 2017Three-dimensional bioprinting and its potential in thefield of articular cartilage regeneration Cartilage
VHM Mouser (2017)
Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles.
J. Malda (2012)
Addition of hydroxyapatite improves stiffness, interconnectivity and osteogenic potential of a highly porous collagen-based scaffold for bone tissue regeneration.
J. P. Gleeson (2010)
Double Network Hydrogels that Mimic the Modulus, Strength, and Lubricity of Cartilage.
A. K. Means (2019)
Morphological characteristics of cartilage-bone transitional structures in the human knee joint and CAD design of an osteochondral scaffold
Weiguo Bian (2016)
Bioprinting of hybrid tissue constructs with tailorable mechanical properties.
W. Schuurman (2011)
LodeA and GelinskyM2015 3Dplotting of growth factor loaded calcium phosphate cement scaffoldsActa Biomater
AR Akkineni (2015)
Structural and rheological properties of methacrylamide modified gelatin hydrogels.
A. Van Den Bulcke (2000)
LodeA andGelinskyM2018Bioprinting ofmineralized constructs utilizingmultichannel plotting of a self-setting calciumphosphate cement and a cell-laden bioink Biofabrication
T Ahlfeld (2018)
J and ItoK 2018Mechanical behavior of a soft hydrogel reinforcedwith three-dimensional printedmicrofibre scaffolds
CastilhoM (2018)
Functionally graded electrospun polycaprolactone and beta-tricalcium phosphate nanocomposites for tissue engineering applications.
C. Erisken (2008)
Assessing bioink shape fidelity to aid material development in 3D bioprinting.
A. Ribeiro (2017)
Out-of-Plane 3D-Printed Microfibers Improve the Shear Properties of Hydrogel Composites
M. de Ruijter (2018)
Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.
R. Levato (2014)
The 'instantaneous' compressive modulus of human articular cartilage in joints of the lower limb.
D. E. Shepherd (1999)
andAtala A 2016A 3Dbioprinting system to produce human-scale tissue constructs with structural integrityNat
KangHW (2016)
andDalton PD2018Out-of-plane 3D-printedmicrofibers improve the shear properties of hydrogel composites
deRuijterM (2018)
Vunjak-NovakovicG andHungCT2008The effect of devitalized trabecular bone on the formation of osteochondral tissue-engineered constructsBiomaterials
EG Lima (2008)
2005Pluronic F127 as a cell encapsulationmaterial: utilization ofmembranestabilizing
S FKhattak (2005)
Suspended Manufacture of Biological Structures.
Samuel Moxon (2017)
Direct writing by way of melt electrospinning.
T. Brown (2011)
Multiphasic construct studied in an ectopic osteochondral defect model
J. Jeon (2014)
2014Chondrocyte redifferentiation and constructmechanical property development in singlecomponent photocrosslinkable hydrogels
PA Levett (2014)
Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs.
Kristel W. M. Boere (2014)
Porosity of 3D biomaterial scaffolds and osteogenesis.
V. Karageorgiou (2005)
PD,HutmacherDWand Malda J 2015Reinforcement of hydrogels using threedimensionally printedmicrofibresNat
J Visser (2015)
A 3D bioprinting system to produce human-scale tissue constructs with structural integrity
Hyun-wook Kang (2016)
Simultaneous Micropatterning of Fibrous Meshes and Bioinks for the Fabrication of Living Tissue Constructs
M. de Ruijter (2019)
2014A biomimeticmulti-layered collagen-based scaffold for osteochondral repairActa Biomater
T JLevingstone (2004)
Self-setting calciumorthophosphate formulations
SV Dorozhkin (2013)
Bioprinting of hybrid tissue constructs with tailorablemechanical propertiesBiofabrication
SchuurmanW (2011)
andWoodfieldTBF2016Newvisiblelight photoinitiating system for improvedprintfidelity in gelatinbased bioinksACSBiomaterials Science&Engineering 2 1752–62
LimKS (2020)
Reinforcement of hydrogels using three-dimensionally printed microfibres.
J. Visser (2015)
A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage.
A. Daly (2016)
2017The bio in the ink: cartilage regenerationwith bioprintable hydrogels and articular cartilage-derived progenitor
R Levato (2017)
Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint.
Jin-Hyung Shim (2016)
Dimension-Based Design of Melt Electrowritten Scaffolds.
Andrei Hrynevich (2018)
From intricate to integrated: Biofabrication of articulating joints
W. M. Groen (2017)
Bioresorbability, porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration?
G. Hannink (2011)
andDalton PD2018 Dimension-based design ofmelt electrowritten scaffolds
HrynevichA (2018)
The incorporation of a zone of calci fi ed cartilage improves the interfacial shear strength between in vitro - formed cartilage and the underlying substrate Acta Biomater
P St-PierreJ (2012)
Preclinical Studies for Cartilage Repair: Recommendations from the International Cartilage Repair Society
M. B. Hurtig (2011)

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Dae Gon Lim (2020)
A Versatile Open-Source Printhead for Low-Cost 3D Microextrusion-Based Bioprinting
A. Sanz-García (2020)
Utilizing an integrated tri-layered scaffold with Titanium-Mesh-Cage base to repair cartilage defects of knee in goat model
Chenjun Zhai (2020)
Polymers for Melt Electrowriting.
Juliane C Kade (2020)
High-resolution electrohydrodynamic bioprinting: a new biofabrication strategy for biomimetic micro/nanoscale architectures and living tissue constructs.
Jiankang He (2020)
Surface Morphology of Three-Dimensionally Printed Replicas of Upper Dental Arches
H. Eliášová (2020)
Bioscaffolds embedded with regulatory modules for cell growth and tissue formation: A review
P. Wang (2021)
Development of a New Bone-Mimetic Surface Treatment Platform: Nanoneedle Hydroxyapatite (nnHA) Coating.
Kian F Eichholz (2020)
Printability and Shape Fidelity of Bioinks in 3D Bioprinting
A. Schwab (2020)
Guidelines for establishing a 3-D printing biofabrication laboratory.
Henry W. Sanicola (2020)
Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region-Dependent Porosity Gradients in an Equine Model
Paweena Diloksumpan (2020)
Melt electrowriting onto anatomically relevant biodegradable substrates: Resurfacing a diarthrodial joint
Q. Peiffer (2020)
Bioprinting stem cells: building physiological tissues one cell at a time.
Chiara Scognamiglio (2020)
Pondering the Potential of Hyaline Cartilage-Derived Chondroprogenitors for Tissue Regeneration: A Systematic Review.
Elizabeth Vinod (2020)
Multitechnology Biofabrication: A New Approach for the Manufacturing of Functional Tissue Structures?
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