Skip to main content
Top
Published in: Journal of Materials Science 12/2015

01-06-2015 | Original Paper

Hierarchically decorated electrospun poly(\( \varepsilon \)-caprolactone)/nanohydroxyapatite composite nanofibers for bone tissue engineering

Authors: Xin Jing, Elizabeth Jin, Hao-Yang Mi, Wan-Ju Li, Xiang-Fang Peng, Lih-Sheng Turng

Published in: Journal of Materials Science | Issue 12/2015

Log in

Activate our intelligent search to find suitable subject content or patents.

search-config
loading …

Abstract

Bone is a nanocomposite comprised of two main components, nanohydroxyapatite (nHA) and Type I collagen. The aim of this study is to mimic the nanotopography of collagen fibrils in bone tissue and to modulate their cellular functions by nanoscale stimulation. Three-dimensional structures consisting of electrospun poly(\( \varepsilon \)-caprolactone) (PCL) and PCL/nHA composite nanofibers decorated by periodically spaced PCL crystal lamellae (shish–kebab structure) were created. It was found that the hierarchically decorated nanostructure not only enhanced the mechanical properties of the scaffolds but also changed the surface wettability behavior of the scaffolds. The enhanced surface wettability facilitated biomimetic mineralization through apatite deposition when exposed to simulated body fluids (SBF). MG-63, an osteosarcoma cell line which behaves similarly to osteoblasts, was used to study the cellular response to the scaffolds. Data suggest kebab crystal nanotopography facilitating cell attachment and proliferation. Functional assays, which quantify alkaline phosphatase (ALP) and calcium expression, revealed increased ALP activity and increased calcium expression on decorated nanofibers. In addition, compared with other scaffolds, the cells on PCL/nHA nanofibrous shish–kebab-structured scaffolds showed obvious extended pseudopodia of the filaments in the cytoskeleton study, demonstrating better interactions between cells and scaffolds.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

  • über 102.000 Bücher
  • über 537 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Finance + Banking
  • Management + Führung
  • Marketing + Vertrieb
  • Maschinenbau + Werkstoffe
  • Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

  • über 67.000 Bücher
  • über 390 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Maschinenbau + Werkstoffe




 

Jetzt Wissensvorsprung sichern!

Literature
1.
go back to reference Weiner S, Wagner HD (1998) The material bone: structure mechanical function relations. Annu Rev Mater Sci 28:271–298CrossRef Weiner S, Wagner HD (1998) The material bone: structure mechanical function relations. Annu Rev Mater Sci 28:271–298CrossRef
2.
go back to reference Weiner S, Traub W (1986) Organization of hydroxyapatite crystals within collagen fibrils. FEBS Lett 206:262–266CrossRef Weiner S, Traub W (1986) Organization of hydroxyapatite crystals within collagen fibrils. FEBS Lett 206:262–266CrossRef
3.
go back to reference Fratzl P, Weinkamer R (2007) Nature’s hierarchical materials. Prog Mater Sci 52:1263–1334CrossRef Fratzl P, Weinkamer R (2007) Nature’s hierarchical materials. Prog Mater Sci 52:1263–1334CrossRef
4.
go back to reference Azami M, Moosavifar MJ, Baheiraei N, Moztarzadeh F, Ai J (2012) Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid. J Biomed Mater Res A 100A:1347–1355CrossRef Azami M, Moosavifar MJ, Baheiraei N, Moztarzadeh F, Ai J (2012) Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid. J Biomed Mater Res A 100A:1347–1355CrossRef
5.
go back to reference Chen JL, Chu B, Hsiao BS (2006) Mineralization of hydroxyapatite in electrospun nanofibrous poly(l-lactic acid) scaffolds. J Biomed Mater Res A 79A:307–317CrossRef Chen JL, Chu B, Hsiao BS (2006) Mineralization of hydroxyapatite in electrospun nanofibrous poly(l-lactic acid) scaffolds. J Biomed Mater Res A 79A:307–317CrossRef
6.
go back to reference Nguyen TH, Bao TQ, Park I, Lee BT (2013) A novel fibrous scaffold composed of electrospun porous poly(epsilon-caprolactone) fibers for bone tissue engineering. J Biomater Appl 28:514–528CrossRef Nguyen TH, Bao TQ, Park I, Lee BT (2013) A novel fibrous scaffold composed of electrospun porous poly(epsilon-caprolactone) fibers for bone tissue engineering. J Biomater Appl 28:514–528CrossRef
7.
go back to reference Jegal SH, Park JH, Kim JH et al (2011) Functional composite nanofibers of poly(lactide-co-caprolactone) containing gelatin-apatite bone mimetic precipitate for bone regeneration. Acta Biomater 7:1609–1617CrossRef Jegal SH, Park JH, Kim JH et al (2011) Functional composite nanofibers of poly(lactide-co-caprolactone) containing gelatin-apatite bone mimetic precipitate for bone regeneration. Acta Biomater 7:1609–1617CrossRef
8.
go back to reference Phipps MC, Clem WC, Grunda JM, Dines GA, Bellis SL (2012) Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials 33:524–534CrossRef Phipps MC, Clem WC, Grunda JM, Dines GA, Bellis SL (2012) Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials 33:524–534CrossRef
9.
go back to reference Xie JW, Li XR, Lipner J et al (2010) “Aligned-to-random” nanofiber scaffolds for mimicking the structure of the tendon-to-bone insertion site. Nanoscale 2:923–926CrossRef Xie JW, Li XR, Lipner J et al (2010) “Aligned-to-random” nanofiber scaffolds for mimicking the structure of the tendon-to-bone insertion site. Nanoscale 2:923–926CrossRef
10.
go back to reference Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK (2002) Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res 60:613–621CrossRef Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK (2002) Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res 60:613–621CrossRef
11.
go back to reference Wutticharoenmongkol P, Sanchavanakit N, Pavasant P, Supaphol P (2006) Preparation and characterization of novel bone scaffolds based on electrospun polycaprolactone fibers filled with nanoparticles. Macromol Biosci 6:70–77CrossRef Wutticharoenmongkol P, Sanchavanakit N, Pavasant P, Supaphol P (2006) Preparation and characterization of novel bone scaffolds based on electrospun polycaprolactone fibers filled with nanoparticles. Macromol Biosci 6:70–77CrossRef
12.
go back to reference Venugopal J, Low S, Choon AT, Kumar AB, Ramakrishna S (2008) Electrospun-modified nanofibrous scaffolds for the mineralization of osteoblast cells. J Biomed Mater Res A 85A:408–417CrossRef Venugopal J, Low S, Choon AT, Kumar AB, Ramakrishna S (2008) Electrospun-modified nanofibrous scaffolds for the mineralization of osteoblast cells. J Biomed Mater Res A 85A:408–417CrossRef
13.
go back to reference Puppi D, Piras AM, Chiellini F et al (2011) Optimized electro- and wet-spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite. J Tissue Eng Regen Med 5:253–263CrossRef Puppi D, Piras AM, Chiellini F et al (2011) Optimized electro- and wet-spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite. J Tissue Eng Regen Med 5:253–263CrossRef
14.
go back to reference Patlolla A, Arinzeh TL (2014) Evaluating apatite formation and osteogenic activity of electrospun composites for bone tissue engineering. Biotechnol Bioeng 111:1000–1017CrossRef Patlolla A, Arinzeh TL (2014) Evaluating apatite formation and osteogenic activity of electrospun composites for bone tissue engineering. Biotechnol Bioeng 111:1000–1017CrossRef
15.
go back to reference Fang M, Goldstein EL, Matich EK, Orr BG, Holl MMB (2013) Type I collagen self-assembly: the roles of substrate and concentration. Langmuir 29:2330–2338CrossRef Fang M, Goldstein EL, Matich EK, Orr BG, Holl MMB (2013) Type I collagen self-assembly: the roles of substrate and concentration. Langmuir 29:2330–2338CrossRef
16.
go back to reference Vetrone F, Variola F, de Oliveira PT et al (2009) Nanoscale oxidative patterning of metallic surfaces to modulate cell activity and fate. Nano Lett 9:659–665CrossRef Vetrone F, Variola F, de Oliveira PT et al (2009) Nanoscale oxidative patterning of metallic surfaces to modulate cell activity and fate. Nano Lett 9:659–665CrossRef
17.
go back to reference Binsberg F (1966) Orientation-induced nucleation in polymer crystallization. Nature 211:516–517CrossRef Binsberg F (1966) Orientation-induced nucleation in polymer crystallization. Nature 211:516–517CrossRef
18.
go back to reference Pennings AJ, Kiel AM (1965) Fractionation of Polymers by Crystallization from Solution. 3. On Morphology of Fibrillar Polyethylene Crystals Grown in Solution. Kolloid Z Z Polym 205:160–162CrossRef Pennings AJ, Kiel AM (1965) Fractionation of Polymers by Crystallization from Solution. 3. On Morphology of Fibrillar Polyethylene Crystals Grown in Solution. Kolloid Z Z Polym 205:160–162CrossRef
19.
go back to reference Li LY, Li CY, Ni CY (2006) Polymer crystallization-driven, periodic patterning on carbon nanotubes. J Am Chem Soc 128:1692–1699CrossRef Li LY, Li CY, Ni CY (2006) Polymer crystallization-driven, periodic patterning on carbon nanotubes. J Am Chem Soc 128:1692–1699CrossRef
20.
go back to reference Chen X, Wang WD, Cheng S, Dong B, Li CY (2013) Mimicking bone nanostructure by combining block copolymer self-assembly and 1D crystal nucleation. ACS Nano 7:8251–8257CrossRef Chen X, Wang WD, Cheng S, Dong B, Li CY (2013) Mimicking bone nanostructure by combining block copolymer self-assembly and 1D crystal nucleation. ACS Nano 7:8251–8257CrossRef
21.
go back to reference Wang XF, Salick MR, Wang XD et al (2013) Poly(epsilon-caprolactone) nanofibers with a self-induced nanohybrid shish-kebab structure mimicking collagen fibrils. Biomacromolecules 14:3557–3569CrossRef Wang XF, Salick MR, Wang XD et al (2013) Poly(epsilon-caprolactone) nanofibers with a self-induced nanohybrid shish-kebab structure mimicking collagen fibrils. Biomacromolecules 14:3557–3569CrossRef
22.
go back to reference Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915CrossRef Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915CrossRef
23.
go back to reference Peng F, Yu XH, Wei M (2011) In vitro cell performance on hydroxyapatite particles/poly(l-lactic acid) nanofibrous scaffolds with an excellent particle along nanofiber orientation. Acta Biomater 7:2585–2592CrossRef Peng F, Yu XH, Wei M (2011) In vitro cell performance on hydroxyapatite particles/poly(l-lactic acid) nanofibrous scaffolds with an excellent particle along nanofiber orientation. Acta Biomater 7:2585–2592CrossRef
24.
go back to reference Rnjak-Kovacina J, Wise SG, Li Z et al (2011) Tailoring the porosity and pore size of electrospun synthetic human elastin scaffolds for dermal tissue engineering. Biomaterials 32:6729–6736CrossRef Rnjak-Kovacina J, Wise SG, Li Z et al (2011) Tailoring the porosity and pore size of electrospun synthetic human elastin scaffolds for dermal tissue engineering. Biomaterials 32:6729–6736CrossRef
25.
go back to reference Croisier F, Duwez AS, Jerome C et al (2012) Mechanical testing of electrospun PCL fibers. Acta Biomater 8:218–224CrossRef Croisier F, Duwez AS, Jerome C et al (2012) Mechanical testing of electrospun PCL fibers. Acta Biomater 8:218–224CrossRef
26.
go back to reference Pirzada T, Arvidson SA, Saquing CD, Shah SS, Khan SA (2012) Hybrid silica-PVA nanofibers via sol-gel electrospinning. Langmuir 28:5834–5844CrossRef Pirzada T, Arvidson SA, Saquing CD, Shah SS, Khan SA (2012) Hybrid silica-PVA nanofibers via sol-gel electrospinning. Langmuir 28:5834–5844CrossRef
27.
go back to reference Zargarian SS, Haddadi-Asl V (2010) A nanofibrous composite scaffold of PCL/hydroxyapatite-chitosan/PVA prepared by electrospinning. Iran Polym J 19:457–468 Zargarian SS, Haddadi-Asl V (2010) A nanofibrous composite scaffold of PCL/hydroxyapatite-chitosan/PVA prepared by electrospinning. Iran Polym J 19:457–468
28.
go back to reference Thomas V, Jagani S, Johnson K et al (2006) Electrospun bioactive nanocomposite scaffolds of polycaprolactone and nanohydroxyapatite for bone tissue engineering. J Nanosci Nanotechnol 6:487–493CrossRef Thomas V, Jagani S, Johnson K et al (2006) Electrospun bioactive nanocomposite scaffolds of polycaprolactone and nanohydroxyapatite for bone tissue engineering. J Nanosci Nanotechnol 6:487–493CrossRef
29.
go back to reference Liao GY, Jiang SB, Xia H, Jiang KF (2012) Preparation and characterization of aligned PLLA/PCL/HA composite fibrous membranes. J Macromol Sci A 49:946–951CrossRef Liao GY, Jiang SB, Xia H, Jiang KF (2012) Preparation and characterization of aligned PLLA/PCL/HA composite fibrous membranes. J Macromol Sci A 49:946–951CrossRef
30.
go back to reference Wang BB, Li B, Xiong J, Li CY (2008) Hierarchically ordered polymer nanofibers via electrospinning and controlled polymer crystallization. Macromolecules 41:9516–9521CrossRef Wang BB, Li B, Xiong J, Li CY (2008) Hierarchically ordered polymer nanofibers via electrospinning and controlled polymer crystallization. Macromolecules 41:9516–9521CrossRef
31.
go back to reference Thomas V, Dean DR, Jose MV, Mathew B, Chowdhury S, Vohra YK (2007) Nanostructured biocomposite scaffolds based on collagen coelectrospun with nanohydroxyapatite. Biomacromolecules 8:631–637CrossRef Thomas V, Dean DR, Jose MV, Mathew B, Chowdhury S, Vohra YK (2007) Nanostructured biocomposite scaffolds based on collagen coelectrospun with nanohydroxyapatite. Biomacromolecules 8:631–637CrossRef
32.
go back to reference Ning NY, Zhang W, Zhao YS, Luo F, Fu Q (2012) Nanohybrid shish kebab structure and its effect on mechanical properties in poly(l-lactide)/carbon nanotube nanocomposite fibers. Polym Int 61:1634–1639CrossRef Ning NY, Zhang W, Zhao YS, Luo F, Fu Q (2012) Nanohybrid shish kebab structure and its effect on mechanical properties in poly(l-lactide)/carbon nanotube nanocomposite fibers. Polym Int 61:1634–1639CrossRef
33.
go back to reference Hench LL, Wilson J (1993) An introduction to bioceramics. World Scientific, LondonCrossRef Hench LL, Wilson J (1993) An introduction to bioceramics. World Scientific, LondonCrossRef
34.
go back to reference Yu SC, Hariram KP, Kumar R, Cheang P, Aik KK (2005) In vitro apatite formation and its growth kinetics on hydroxyapatite/polyetheretherketone biocomposites. Biomaterials 26:2343–2352CrossRef Yu SC, Hariram KP, Kumar R, Cheang P, Aik KK (2005) In vitro apatite formation and its growth kinetics on hydroxyapatite/polyetheretherketone biocomposites. Biomaterials 26:2343–2352CrossRef
35.
go back to reference Rodriguez K, Renneckar S, Gatenholm P (2011) Biomimetic calcium phosphate crystal mineralization on electrospun cellulose-based scaffolds. Acs Appl Mater Interfaces 3:681–689CrossRef Rodriguez K, Renneckar S, Gatenholm P (2011) Biomimetic calcium phosphate crystal mineralization on electrospun cellulose-based scaffolds. Acs Appl Mater Interfaces 3:681–689CrossRef
36.
go back to reference Yang F, Wolke JGC, Jansen JA (2008) Biomimetic calcium phosphate coating on electrospun poly (epsilon-caprolactone) scaffolds for bone tissue engineering. Chem Eng J 137:154–161CrossRef Yang F, Wolke JGC, Jansen JA (2008) Biomimetic calcium phosphate coating on electrospun poly (epsilon-caprolactone) scaffolds for bone tissue engineering. Chem Eng J 137:154–161CrossRef
37.
go back to reference Li MM, Liu WW, Sun JS et al (2013) Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering. Acs Appl Mater Interfaces 5:5921–5926CrossRef Li MM, Liu WW, Sun JS et al (2013) Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering. Acs Appl Mater Interfaces 5:5921–5926CrossRef
38.
go back to reference Mi HY, Jing X, Salick MR, Cordie TM, Peng XF, Turng LS (2014) Morphology, mechanical properties, and mineralization of rigid thermoplastic polyurethane/hydroxyapatite scaffolds for bone tissue applications: effects of fabrication approaches and hydroxyapatite size. J Mater Sci 49:2324–2337. doi:10.1007/s10853-013-7931-3 CrossRef Mi HY, Jing X, Salick MR, Cordie TM, Peng XF, Turng LS (2014) Morphology, mechanical properties, and mineralization of rigid thermoplastic polyurethane/hydroxyapatite scaffolds for bone tissue applications: effects of fabrication approaches and hydroxyapatite size. J Mater Sci 49:2324–2337. doi:10.​1007/​s10853-013-7931-3 CrossRef
39.
go back to reference Shor L, Guceri S, Wen XJ, Gandhi M, Sun W (2007) Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro. Biomaterials 28:5291–5297CrossRef Shor L, Guceri S, Wen XJ, Gandhi M, Sun W (2007) Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro. Biomaterials 28:5291–5297CrossRef
40.
go back to reference Lee HJ, Kim SE, Choi HW, Kim CW, Kim KJ, Lee SC (2007) The effect of surface-modified nano-hydroxyapatite on biocompatibility of poly(epsilon-caprolactone)/hydroxyapatite nanocomposites. Eur Polym J 43:1602–1608CrossRef Lee HJ, Kim SE, Choi HW, Kim CW, Kim KJ, Lee SC (2007) The effect of surface-modified nano-hydroxyapatite on biocompatibility of poly(epsilon-caprolactone)/hydroxyapatite nanocomposites. Eur Polym J 43:1602–1608CrossRef
41.
go back to reference Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF (2001) Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials 22:87–96CrossRef Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF (2001) Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials 22:87–96CrossRef
42.
go back to reference Golub EE, Harrison G, Taylor AG, Camper S, Shapiro IM (1992) The role of alkaline-phosphatase in cartilage mineralization. Bone Miner 17:273–278CrossRef Golub EE, Harrison G, Taylor AG, Camper S, Shapiro IM (1992) The role of alkaline-phosphatase in cartilage mineralization. Bone Miner 17:273–278CrossRef
43.
go back to reference Woo KM, Chen VJ, Ma PX (2003) Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J Biomed Mater Res A 67A:531–537CrossRef Woo KM, Chen VJ, Ma PX (2003) Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J Biomed Mater Res A 67A:531–537CrossRef
44.
go back to reference Shi LY, Aid R, Le Visage C, Chew SY (2012) Biomimicking polysaccharide nanofibers promote vascular phenotypes: a potential application for vascular tissue engineering. Macromol Biosci 12:395–401CrossRef Shi LY, Aid R, Le Visage C, Chew SY (2012) Biomimicking polysaccharide nanofibers promote vascular phenotypes: a potential application for vascular tissue engineering. Macromol Biosci 12:395–401CrossRef
45.
go back to reference Jiang X, Cao HQ, Shi LY, Ng SY, Stanton LW, Chew SY (2012) Nanofiber topography and sustained biochemical signaling enhance human mesenchymal stem cell neural commitment. Acta Biomater 8:1290–1302CrossRef Jiang X, Cao HQ, Shi LY, Ng SY, Stanton LW, Chew SY (2012) Nanofiber topography and sustained biochemical signaling enhance human mesenchymal stem cell neural commitment. Acta Biomater 8:1290–1302CrossRef
46.
go back to reference Kilian KA, Bugarija B, Lahn BT, Mrksich M (2010) Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA 107:4872–4877CrossRef Kilian KA, Bugarija B, Lahn BT, Mrksich M (2010) Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA 107:4872–4877CrossRef
47.
go back to reference McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6:483–495CrossRef McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6:483–495CrossRef
Metadata
Title
Hierarchically decorated electrospun poly(-caprolactone)/nanohydroxyapatite composite nanofibers for bone tissue engineering
Authors
Xin Jing
Elizabeth Jin
Hao-Yang Mi
Wan-Ju Li
Xiang-Fang Peng
Lih-Sheng Turng
Publication date
01-06-2015
Publisher
Springer US
Published in
Journal of Materials Science / Issue 12/2015
Print ISSN: 0022-2461
Electronic ISSN: 1573-4803
DOI
https://doi.org/10.1007/s10853-015-8933-0

Other articles of this Issue 12/2015

Journal of Materials Science 12/2015 Go to the issue

Premium Partners