Altering invivo macrophage responses with modified polymer properties

Biomaterials

Volumn 56, Issue , 2015, Pages 187-197

  Bygd, Hannah C ^a   Forsmark, Kiva D ^a   Bratlie, Kaitlin M ^a,b  

^a Iowa State University   (United States)

^b IOWA STATE UNIVERSITY   (United States)

Author keywords

Biocompatibility; Biomedical applications; Invivo test; Macrophage phenotype; Polymer properties; Surface modification

Indexed keywords

ACRYLIC MONOMERS; ACTIVATION ANALYSIS; AMIDES; BIOCOMPATIBILITY; CHEMICAL ACTIVATION; COMPUTATIONAL CHEMISTRY; FUNCTIONAL POLYMERS; MEDICAL APPLICATIONS; POLARIZATION; SURFACE CHEMISTRY; SURFACE TREATMENT;

BIOMATERIAL IMPLANTATION; BIOMEDICAL APPLICATIONS; CHEMICAL AND PHYSICAL PROPERTIES; IN-VIVO TESTS; MACROPHAGE PHENOTYPES; N- ISOPROPYLACRYLAMIDE; POLYMER PROPERTIES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP METHODS;

MACROPHAGES;

ACETAL; ALKENE; AMIDE; ARGINASE; COPOLYMER; EPOXIDE; ESTER; ETHER; GLYCERYL TRINITRATE; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 10; KETONE; NANOPARTICLE; OXIME; PHOSPHONIC ACID DERIVATIVE; POLY(N ISOPROPYLACRYLAMIDE CO ACRYLIC ACID); POLY(N ISOPROPYLACRYLAMIDE); POLYACRYLIC ACID; SULFONE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ACRYLAMIDE DERIVATIVE; BIOMATERIAL; CYTOKINE; N-ISOPROPYLACRYLAMIDE-ACRYLIC ACID COPOLYMER; NOS2 PROTEIN, MOUSE; POLYMER;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOCOMPATIBILITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME ACTIVITY; FEMALE; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MACROPHAGE ACTIVATION; MACROPHAGE FUNCTION; MACROPHAGE RESPONSE; MONOCYTE; MOUSE; NONHUMAN; PHENOTYPE; POLARIZATION; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; SURFACE PROPERTY; TISSUE ENGINEERING; ANIMAL; CHEMISTRY; CYTOLOGY; DRUG DELIVERY SYSTEM; MACROPHAGE; MATERIALS TESTING; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

ACRYLAMIDES; ANIMALS; ARGINASE; BIOCOMPATIBLE MATERIALS; CYTOKINES; DRUG DELIVERY SYSTEMS; FEMALE; MACROPHAGE ACTIVATION; MACROPHAGES; MAGNETIC RESONANCE SPECTROSCOPY; MATERIALS TESTING; MICE; NANOPARTICLES; NITRIC OXIDE SYNTHASE TYPE II; PHENOTYPE; POLYMERS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PROPERTIES;

EID: 84928386445     PISSN: 01429612     EISSN: 18785905     Source Type: Journal    
DOI: 10.1016/j.biomaterials.2015.03.042     Document Type: Article

References (91)

1. Stout R.D., Watkins S.K., Suttles J. Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages. JLeukoc Biol 2009, 86:1105-1109. 10.1189/jlb.0209073.
2. Martinez F.O., Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014, 6:1-13. 10.12703/P6-13.
3. Murray P.J., Allen J.E., Biswas S.K., Fisher E.A., Gilroy D.W., Goerdt S., et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014, 41:14-20. 10.1016/j.immuni.2014.06.008.
4. Xue J., Schmidt S.V., Sander J., Draffehn A., Krebs W., Quester I., et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014, 40:274-288. 10.1016/j.immuni.2014.01.006.
5. Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008, 8:958-969. 10.1038/nri2448.
6. Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010, 11:889-896. 10.1038/ni.1937.
7. Sica A., Mantovani A. Macrophage plasticity and polarization: invivo veritas. JClin Invest 2012, 122:787-795. 10.1172/JCI59643DS1.
8. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004, 25:677-686. 10.1016/j.it.2004.09.015.
9. Sica A., Schioppa T., Mantovani A., Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 2006, 42:717-727. 10.1016/j.ejca.2006.01.003.
10. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Front Biosci 2008, 13:453-461.
11. Biswas S.K., Chittezhath M., Shalova I.N., Lim J.-Y. Macrophage polarization and plasticity in health and disease. Immunol Res 2012, 53:11-24. 10.1007/s12026-012-8291-9.
12. Gordon S., Martinez F.O. Alternative activation of macrophages: mechanism and functions. Immunity 2010, 32:593-604. 10.1016/j.immuni.2010.05.007.
13. Martinez F.O., Helming L., Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 2009, 27:451-483. 10.1146/annurev.immunol.021908.132532.
14. Zhang Y., Choksi S., Chen K., Pobezinskaya Y., Linnoila I., Liu Z.-G. ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res 2013, 23:898-914. 10.1038/cr.2013.75.
15. Stout R.D., Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. JLeukoc Biol 2004, 76:509-513. 10.1189/jlb.0504272.
16. Stout R.D., Jiang C., Matta B., Tietzel I., Watkins S.K., Suttles J. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. JImmunol 2005, 175:342-349. 10.4049/jimmunol.175.1.342.
17. Kenneth Ward W. Areview of the foreign-body response to subcutaneously-implanted devices: the role of macrophages and cytokines in biofouling and fibrosis. JDiabetes Sci Technol 2008, 2:768-777.
18. Xia Z., Triffitt J.T. Areview on macrophage responses to biomaterials. Biomed Mater 2006, 1:R1-R9. 10.1088/1748-6041/1/1/R01.
19. Higgins D.M., Basaraba R.J., Hohnbaum A.C., Lee E.J., Grainger D.W., Gonzalez-Juarrero M. Localized immunosuppressive environment in the foreign body response to implanted biomaterials. Am J Pathol 2009, 175:161-170. 10.2353/ajpath.2009.080962.
20. Mantovani A., Biswas S.K., Galdiero M.R., Sica A., Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. JPathol 2013, 229:176-185. 10.1002/path.4133.
21. Gretzer C., Emanuelsson L., Liljensten E., Thomsen P. The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials. JBiomater Sci Polym Ed 2006, 17:669-687.
22. Murray P.J., Wynn T.A. Obstacles and opportunities for understanding macrophage polarization. JLeukoc Biol 2011, 89:557-563. 10.1189/jlb.0710409.
23. Le S.J., Gongora M., Zhang B., Grimmond S., Campbell G.R., Campbell J.H., et al. Gene expression profile of the fibrotic response in the peritoneal cavity. Differentiation 2010, 79:232-243. 10.1016/j.diff.2010.03.001.
24. Garg K., Pullen N.A., Oskeritzian C.A., Ryan J.J., Bowlin G.L. Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials 2013, 34:4439-4451. 10.1016/j.biomaterials.2013.02.065.
25. Bridges A.W., Singh N., Burns K.L., Babensee J.E., Andrew Lyon L., García A.J. Reduced acute inflammatory responses to microgel conformal coatings. Biomaterials 2008, 29:4605-4615. 10.1016/j.biomaterials.2008.08.015.
26. Fukano Y., Usui M.L., Underwood R.A., Isenhath S., Marshall A.J., Hauch K.D., et al. Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice. JBiomed Mater Res A 2010, 94:1172-1186. 10.1002/jbm.a.32798.
27. Bartneck M., Heffels K.-H., Bovi M., Groll J., Zwadlo-Klarwasser G. The role of substrate morphology for the cytokine release profile of immature human primary macrophages. Mater Sci Eng C Mater Biol Appl 2013, 33:5109-5114. 10.1016/j.msec.2013.08.028.
28. Chen S., Jones J a., Xu Y., Low H.-Y., Anderson J.M., Leong K.W. Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials 2010, 31:3479-3491. 10.1016/j.biomaterials.2010.01.074.
29. Barbosa J.N., Amaral I.F., Aguas A.P., Barbosa M.A. Evaluation of the effect of the degree of acetylation on the inflammatory response to 3D porous chitosan scaffolds. JBiomed Mater Res A 2010, 93:20-28. 10.1002/jbm.a.32499.
30. Bygd H.C., Forsmark K.D., Bratlie K.M. The significance of macrophage phenotype in cancer and biomaterials. Clin Transl Med 2014, 3.
31. Squadrito M.L., De Palma M. Macrophage regulation of tumor angiogenesis: implications for cancer therapy. Mol Asp Med 2011, 32:123-145. 10.1016/j.mam.2011.04.005.
32. Solinas G., Germano G., Mantovani A., Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. JLeukoc Biol 2009, 86:1065-1073. 10.1189/jlb.0609385.
33. Heusinkveld M., van der Burg S.H. Identification and manipulation of tumor associated macrophages in human cancers. JTransl Med 2011, 9:216. 10.1186/1479-5876-9-216.
34. Jinushi M., Chiba S., Yoshiyama H., Masutomi K., Kinoshita I., Dosaka-Akita H., et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci U S A 2011, 108:12425-12430. 10.1073/pnas.1106645108.
35. Mantovani A., Schioppa T., Porta C., Allavena P., Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 2006, 25:315-322. 10.1007/s10555-006-9001-7.
36. Ramanathan S., Jagannathan N. Tumor associated macrophage: A review on the phenotypes, traits and functions. Iran J Cancer Prev 2014, 7:1-8.
37. Quatromoni J.G., Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am J Transl Res 2012, 4:376-389.
38. Dunn W.J. Quantitative structure-activity relationships (QSAR). Chemom Intell Lab Syst 1989, 6:181-190.
39. Kubinyi H. QSAR and 3D QSAR in drug design part 1: methodology. Drug Discov Today 1997, 2:457-467. 10.1016/S1359-6446(97)01079-9.
40. Eriksson L., Jaworska J., Worth A.P., Cronin M.T.D., McDowell R.M., Gramatica P. Methods for reliability and uncertainty assessment and for applicability evaluations of classification-and regression-based QSARs. Environ Health Perspect 2003, 111:1361-1375. 10.1289/ehp.5758.
41. Hansch C., Steinmetz W.E., Leo A.J., Mekapati S.B., Kurup A., Hoekman D. On the role of polarizability in chemical-biological interactions. JChem Inf Model 2003, 43:120-125.
42. Petersen L.K., Xue L., Wannemuehler M.J., Rajan K., Narasimhan B. The simultaneous effect of polymer chemistry and device geometry on the invitro activation of murine dendritic cells. Biomaterials 2009, 30:5131-5142. 10.1016/j.biomaterials.2009.05.069.
43. Li X., Petersen L., Broderick S., Narasimhan B., Rajan K. Identifying factors controlling protein release from combinatorial biomaterial libraries via hybrid data mining methods. ACS Comb Sci 2011, 13:50-58. 10.1021/co100019d.
44. Petersen L.K., Ramer-Tait A.E., Broderick S.R., Kong C.-S., Ulery B.D., Rajan K., et al. Activation of innate immune responses in a pathogen-mimicking manner by amphiphilic polyanhydride nanoparticle adjuvants. Biomaterials 2011, 32:6815-6822. 10.1016/j.biomaterials.2011.05.063.
45. Wang D., Phan N., Isely C., Bruene L., Bratlie K.M. Effect of surface modification and macrophage phenotype on particle internalization. Biomacromolecules 2014, Epub:A - I.
46. Akilbekova D., Philiph R., Graham A., Bratlie K.M. Macrophage reprogramming: influence of latex beads with various functional groups on macrophage phenotype and phagocytic uptake invitro. JBiomed Mater Res Part A 2015, 103:262-268.
47. Doshi N., Mitragotri S. Macrophages recognize size and shape of their targets. PLoS One 2010, 5. e10051. 10.1371/journal.pone.0010051.
48. Walkey C.D., Olsen J.B., Guo H., Emili A., Chan W.C.W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. JAm Chem Soc 2012, 134:2139-2147. 10.1021/ja2084338.
49. Decuzzi P., Pasqualini R., Arap W., Ferrari M. Intravascular delivery of particulate systems: does geometry really matter?. Pharm Res 2009, 26:235-243. 10.1007/s11095-008-9697-x.
50. Zaveri T.D., Dolgova N.V., Chu B.H., Lee J., Wong J., Lele T.P., et al. Contributions of surface topography and cytotoxicity to the macrophage response to zinc oxide nanorods. Biomaterials 2010, 31:2999-3007. 10.1016/j.biomaterials.2009.12.055.
51. Bota P.C.S., Collie A.M.B., Puolakkainen P., Vernon R.B., Sage E.H., Ratner B.D., et al. Biomaterial topography alters healing invivo and monocyte/macrophage activation invitro. JBiomed Mater Res A 2010, 95:649-657. 10.1002/jbm.a.32893.
52. Weissleder R., Tung C., Mahmood U., Bogdanov A. Invivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999, 17:375-378.
53. Levinson S.S. Kinetic centrifugal analyzer and manual determination of serum urea nitrogen, with use of o-phthaldialdehyde reagent. Clin Chem 1978, 24:2199-2202.
54. Bicerano J. Prediction of polymer properties 2002, CRC Press.
55. Dimitrijević M., Aleksić I., Vujić V., Stanojević S., Pilipović I., von Hörsten S., et al. Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1β expression ratio and preserved NO/urea ratio following LPS-stimulation invitro. Age (Omaha) 2014, 36. 10.1007/s11357-014-9696-2.
56. Wynn T.A., Barron L., Thompson R.W., Madala S.K., Wilson M.S., Cheever A.W., et al. Quantitative assessment of macrophage functions in repair and fibrosis. Curr Protoc Essent Lab Tech 2011, 2011:1-12. 10.1002/0471142735.im1422s93.
57. Whyte C.S., Bishop E.T., Ruckerl D., Gaspar-Pereira S., Barker R.N., Allen J.E., et al. Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. JLeukoc Biol 2011, 90:845-854. 10.1189/jlb.1110644.
58. Guo X., Stroup S.E., Houpt E.R. Persistence of Entamoeba histolytica infection in CBA mice owes to intestinal IL-4 production and inhibition of protective IFN-gamma. Mucosal Immunol 2008, 1:139-146. 10.1038/mi.2007.18.
59. Anderson J.M., Rodriguez A., Chang D.T. Foreign body reaction to biomaterials. Semin Immunol 2008, 20:86-100. 10.1016/j.smim.2007.11.004.
60. Bratlie K.M., Dang T.T., Lyle S., Nahrendorf M., Weissleder R., Langer R., et al. Rapid biocompatibility analysis of materials via invivo fluorescence imaging of mouse models. PLoS One 2010, 5. e10032. 10.1371/journal.pone.0010032.
61. Grainger D.W. All charged up about implanted biomaterials. Nat Biotechnol 2013, 31:507-509. 10.1038/nbt.2600.
62. Lominadze G., Powell D.W., Luerman G.C., Link A.J., Ward R.A., McLeish K.R. Proteomic analysis of human neutrophil granules. Mol Cell Proteomics 2005, 4:1503-1521. 10.1074/mcp.M500143-MCP200.
63. Faurschou M., Borregaard N. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 2003, 5:1317-1327. 10.1016/j.micinf.2003.09.008.
64. Berchem G., Glondu M., Gleizes M., Brouillet J., Garcia M., Liaudet-coopman E. Cathepsin-D affects multiple tumor progression steps invivo: proliferation, angiogenesis and apoptosis. Oncogene 2002, 21:5951-5955. 10.1038/sj.onc.1205745.
65. Diment S., Leech M.S., Stahls P.D. Cathepsin D is membrane-associated in Macrophage Endosomes. JBiol Chem 1988, 263:6901-6907.
66. Yasuda Y., Li Z., Bogyo M., Brömme D., Greenbaum D., Weber E., et al. Cathepsin V, a novel and potent elastolytic activity expressed in activated macrophages. JBiol Chem 2004, 279:36761-36770. 10.1074/jbc.M403986200.
67. Schwarz A., Schirmeister T., Reinheckel T., Gonzalez-leal I.J., Ro B., Lutz M.B., et al. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during leishmania major infection. PLoS Negl Trop Dis 2014, 8. e3194. 10.1371/journal.pntd.0003194.
68. Shree T., Olson O.C., Elie B.T., Kester J.C., Garfall A.L., Simpson K., et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev 2011, 25:2465-2479. 10.1101/gad.180331.111.5.
69. Shi B.G., Bryant R.A.R., Riese R., Verhelst S., Driessen C., Li Z., et al. Role for Cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. JExp Med 2000, 191:1177-1185.
70. Vasiljeva O., Papazoglou A., Kru A., Brodoefel H., Korovin M., Deussing J., et al. Tumor cell-derived and macrophage-derived Cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res 2006, 66:5242-5251. 10.1158/0008-5472.CAN-05-4463.
71. Balkwill F. Tumor necrosis factor or tumor promoting factor?. Cytokine Growth Factor Rev 2002, 13:135-141. 10.1016/S1359-6101(01)00020-X.
72. Szlosarek P., Charles K.A., Balkwill F.R. Tumour necrosis factor-alpha as a tumour promoter. Eur J Cancer 2006, 42:745-750. 10.1016/j.ejca.2006.01.012.
73. Brown B.N., Ratner B.D., Goodman S.B., Amar S., Badylak S.F. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 2012, 33:3792-3802. 10.1016/j.biomaterials.2012.02.034.
74. Kigerl K a., Gensel J.C., Ankeny D.P., Alexander J.K., Donnelly D.J., Popovich P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. JNeurosci 2009, 29:13435-13444. 10.1523/JNEUROSCI.3257-09.2009.
75. Pesce J.T., Ramalingam T.R., Mentink-Kane M.M., Wilson M.S., El Kasmi K.C., Smith A.M., et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog 2009, 5. e1000371. 10.1371/journal.ppat.1000371.
76. Witte M.B., Barbul A. Arginine physiology and its implication for wound healing. Wound Repair Regen 2003, 11:419-423.
77. Kubinyi H. Methods and principles in medicinal chemistry 1993, Wiley Online Library.
78. Wang D., Bratlie K.M. Influence of polymer chemistry on cytokine secretion from polarized macrophages. Biomater Sci Eng 2015, 1:166-174.
79. Tangpasuthadol V., Pongchaisirikul N., Hoven V.P. Surface modification of chitosan films. Effects of hydrophobicity on protein adsorption. Carbohydr Res 2003, 338:937-942.
80. Wang K., Zhou C., Hong Y., Zhang X. Areview of protein adsorption on bioceramics. Interface Focus 2012, 2:259-277.
81. Rokstad A.M., Lacík I., de Vos P., Strand B.L. Advances in biocompatibility and physico-chemical characterization of microspheres for cell encapsulation. Adv Drug Deliv Rev 2014, 67-68:111-130. 10.1016/j.addr.2013.07.010.
82. Kao W. Evaluation of protein-modulated macrophage behavior on biomaterials: designing biomimetic materials for cellular engineering. Biomaterials 1999, 20:2213-2221. 10.1016/S0142-9612(99)00152-0.
83. Kao W.J., Hubbell J.A., Anderson J.M. Protein-mediated macrophage adhesion and activation on biomaterials: a model for modulating cell behavior. JMater Sci Mater Med 1999, 10:601-605.
84. Bacakova L., Filova E., Parizek M., Ruml T., Svorcik V. Modulation of cell adhesion, proliferation and differentiation on materials designed for body implants. Biotechnol Adv 2011, 29:739-767. 10.1016/j.biotechadv.2011.06.004.
85. McBane J.E., Ebadi D., Sharifpoor S., Labow R.S., Santerre J.P. Differentiation of monocytes on a degradable, polar, hydrophobic, ionic polyurethane: two-dimensional films vs. three-dimensional scaffolds. Acta Biomater 2011, 7:115-122. 10.1016/j.actbio.2010.08.014.
86. McBane J.E., Sharifpoor S., Cai K., Labow R.S., Santerre J.P. Biodegradation and invivo biocompatibility of a degradable, polar/hydrophobic/ionic polyurethane for tissue engineering applications. Biomaterials 2011, 32:6034-6044. 10.1016/j.biomaterials.2011.04.048.
87. Hollinger J.O. An introduction to biomaterials 2011, 2nd ed.
88. Beningo K.A., Wang Y. Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. JCell Sci 2002, 115:849-856.
89. Van Oss C.J. Phagocytosis as a surface phenomenon. Annu Rev Microbiol 1978, 32:19-39.
90. De Vos P., de Haan B.J., Kamps J.A.A.M., Faas M.M., Kitano T. Zeta-potentials of alginate-PLL capsules: a predictive measure for biocompatibility?. JBiomed Mater Res Part A 2006, 813-819. 10.1002/jbm.a.
91. De Vos P., Spasojevic M., de Haan B.J., Faas M.M. The association between invivo physicochemical changes and inflammatory responses against alginate based microcapsules. Biomaterials 2012, 33:5552-5559. 10.1016/j.biomaterials.2012.04.039.