Investigation of potential injectable polymeric biomaterials for bone regeneration

Journal of Biomedical Materials Research - Part A

Volumn 101 A, Issue 8, 2013, Pages 2436-2447

  Dreifke, Michael B ^a   Ebraheim, Nabil A ^a   Jayasuriya, Ambalangodage C ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

biocompatibility; biodegradation; bone regeneration; gel; injectable; microspheres; polymer; stem cells

Indexed keywords

BONE REGENERATION; BONE TISSUE REGENERATION; INJECTABLE; INJECTABLE BIOMATERIALS; MINIMALLY INVASIVE TREATMENTS; ORTHOPEDIC APPLICATIONS; POLY(PROPYLENE FUMARATE); POLYMERIC BIOMATERIALS;

BIOCOMPATIBILITY; BIODEGRADABLE POLYMERS; BIODEGRADATION; BIOLOGICAL MATERIALS; BONE; COPOLYMERS; CROSSLINKING; DEFECTS; ETHYLENE; GELS; HYDROGELS; MICROBIOLOGY; MICROSPHERES; POLYETHYLENE GLYCOLS; POLYETHYLENE OXIDES; POLYMERS; PROPYLENE; STEM CELLS;

SCAFFOLDS (BIOLOGY);

ALGINIC ACID; BIOMATERIAL; BONE MORPHOGENETIC PROTEIN 2; CHITOSAN; FUMARIC ACID DERIVATIVE; HYALURONIC ACID; HYDROXYAPATITE; MACROGOL; MICROSPHERE; POLY (PROPYLENE FUMARATE); POLYGLACTIN; POLYMER; PROPYLENE GLYCOL; UNCLASSIFIED DRUG;

BIOCOMPATIBILITY; BIODEGRADATION; BONE REGENERATION; BONE TISSUE; CELL ADHESION; CELL DIFFERENTIATION; CELL FUNCTION; CELL VIABILITY; CHEMICAL STRUCTURE; CROSS LINKING; EXTRACELLULAR MATRIX; GEL; HUMAN; HYDROGEL; HYDROPHILICITY; HYDROPHOBICITY; IN VITRO STUDY; IN VIVO STUDY; MICRO-COMPUTED TOMOGRAPHY; MOLECULAR WEIGHT; OSSIFICATION; OSTEOBLAST; POLYMERIZATION; POROSITY; REVIEW; STATIC ELECTRICITY; TISSUE ENGINEERING;

ANIMALS; BIOCOMPATIBLE MATERIALS; BONE REGENERATION; GELS; HUMANS; INJECTIONS; POLYMERS;

EID: 84879502681     PISSN: 15493296     EISSN: 15524965     Source Type: Journal    
DOI: 10.1002/jbm.a.34521     Document Type: Review

References (97)

1. Grabowski P,. Physiology of bone. Endocr Dev 2009; 16: 32-48.
2. Friedenstein AJ,. Sromal mechanocytes of bone marrow: cloning in vitro and retransplantation in vivo, In: Immunology of Bone Marrow Transplantation. Berlin: Springer-Verlag; 1980, p 19-29.
3. Rees DC, Haddad FS., Bone transplantation. Hosp Med 2003; 64: 205-209.
4. Conway JD,. Autograft and nonunions: morbidity with intramedullary bone graft versus iliac crest bone graft. Orthop Clin North Am 2010; 41: 75-84.
5. Nuss KM, von Rechenberg B,. Biocompatibility issues with modern implants in bone-a review for clinical orthopedics. Open Orthop J 2008; 25: 66-78.
6. Reddi AH,. Bone morphogenetic stromal proteins, bone marrow cells, and mesenchymal stem cells: Maureen Owen revisited. Clin Orthop 1995; 313: 115-119.
7. Kempen DH, Kruyt MC, Lu L, Wilson CE, Florschutz AV, Creemers LB, Yaszemski MJ, Dhert WJ,. Effect of autologous bone marrow stromal cell seeding and bone morphogenetic protein-2 delivery on ectopic bone formation in a microsphere/poly(propylene fumarate) composite. Tissue Eng Part A. 2009; 15: 587-594.
8. Hollinger J,. Strategies for regenerating bone of the craniofacial complex. Bone 1993; 14: 575-580.
9. Kim IY, Seo SJ, Moon HS, Yoo MK, Park IY, Kim BC,. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv 2008; 26: 1-21.
10. Martínez-Sanz E, Ossipov DA, Hilborn J, Larsson S, Jonsson KB, Varghese OP,. Bone reservoir: injectable hyaluronic acid hydrogel for minimal invasive bone augmentation. J Control Release 2011; 152: 232-240.
11. Dupont KM, Sharma K, Stevens HY, Boerckel JD, Garcia AJ, Guldberg RE,. Human stem cell delivery for treatment of large segmental bone defects. Proc Natl Acad Sci USA 2010; 107: 3305-3310.
12. Burguera EF, Xu HH, Sun L,. Injectable calcium phosphate cement: effects of powder-to-liquid ratio and needle size. J Biomed Mater Res B Appl Biomater 2008; 84: 493-502.
13. Hedberg EL, Shih CK, Lemoine JJ, Timmer MD, Liebschner MA, Jansen JA, Mikos AG., In vitro degradation of porous poly(propylene fumarate)/poly(DL -Lactic-co-glycolic acid) composite scaffolds. Biomaterials 2005; 26: 3215-3225.
14. Jiang T, Kumbar SG, Nair LS, Laurencin CT,. Biologically active chitosan systems for tissue engineering and regenerative medicine. Curr Top Med Chem 2008; 8: 354-364.
15. Augst AD, Kong HJ, Mooney DJ,. Alginate hydrogels as biomaterials. Macromol Biosci 2006; 6: 623-633.
16. Gutowska A, Jeong B, Jasionowski M,. Injectable gels for tissue engineering. Anat Record 2001; 263: 342-349.
17. Jayasuriya AC, Shah C,. Controlled release of insulin like growth factor-1 and bone marrow stromal cell function of bone-like mineral layers coated PLGA scaffolds. J Tissue Eng Regen Med 2008; 2: 43-49.
18. RuHé PQ, Hedberg EL, Padron NT, Spauwen PH, Jansen JA, Mikos AG,. Biocompatibility and degradation of poly(DL -lactic-co-glycolic acid)/calcium phosphate cement composites. J Biomed Mater Res A 2005; 74: 533-544.
19. Kang SW, Yang HS, Seo SW, Han DK, Kim BS,. Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering. J Biomed Mater Res A 2008; 85: 747-756.
20. Shi X, Wang Y, Ren L, Gong Y, Wang DA,. Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications. Pharm Res 2009; 26: 422-430.
21. Ji Y, Xu GP, Zhang ZP, Xia JJ, Yan JL, Pan SH. BMP-, 2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering. Ann Biomed Eng 2010; 38: 632-639.
22. Shi X, Wang Y, Varshney RR, Ren L, Gong Y, Wang D,. Microsphere-based drug releasing scaffolds for inducing osteogenesis of human mesenchymal stem cells in vitro. Euro J Pharm Sci 2010; 39: 59-67.
23. Yoon SJ, Kim SH, Ha HJ, Ko YK, So JW, Kim MS, Yang Y, Khang G, Rhee JM, Lee HB,. Reduction of inflammatory reaction of poly(DL -lactic-co-glycolic acid) using demineralized bone particles. Tissue Eng Part A 2008; 14: 539-547.
24. Liu H, Slamovich EB, Webster TJ,. Less harmful acidic degradation of poly(lacticoco-glycolic acid) bone tissue engineering scaffolds through titania nanoparticle addition. Int J Nanomed 2006; 1: 541-545.
25. Peter SJ, Yaszemski MJ, Suggs LJ, Payne RG, Langer R, Hayes WC, Unroe MR, Alemany LB, Engel PS, Mikos AG,. Characterization of partially saturated poly(propylene fumarate) for orthopaedic application. J Biomater Sci Polym Ed 1997; 8: 893-904.
26. Vehof JW, Fisher JP, Dean D, van der Waerden JP, Spauwen PH, Mikos AG, Jansen JA,. Bone formation in transforming growth factor beta-1 coated porous poly (propylene fumarate) scaffolds. J Biomed Mater Res 2002; 60: 241-251.
27. Kim CW, Talac R, Lu L, Moore MJ, Currier BL, Yaszemski MJ,. Characterization of porous injectable poly-(propylene fumarate)-based bone graft substitute. J Biomed Mater Res A 2008; 85: 1114-1119.
28. Kempen DH, Lu L, Zhu X, Kim C, Jabbari E, Dhert WJ, Currier BL, Yaszemski MJ,. Development of biodegradable poly(propylene fumarate)/poly(lactic-co- glycolic acid) blend microspheres: I. Preparation and characterization. J Biomed Mater Res A 2004; 70: 283-292.
29. Kempen DH, Lu L, Kim C, Zhu X, Dhert WJ, Currier BL, Yaszemski MJ,. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate). J Biomed Matr Res A 2006; 77: 103-111.
30. Wang Y, Wan C, Szöke G, Ryaby JT, Li G,. Local injection of thrombin-related peptide (TP508) in PPF/PLGA microparticles-enhanced bone formation during distraction osteogenesis. J Orthop Res 2008; 26: 539-546.
31. Mistry AS, Pham QP, Schouten C, Yeh T, Christenson EM, Mikos AG, Jansen JA,. In vivo bone biocompatibility and degradation of porous fumarate-based polymer/alumoxane nanocomposites for bone tissue engineering. J Biomed Mater Res A 2010; 92: 451-462.
32. Di Martino A, Sittinger M, Risbud MV,. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials 2005; 26: 5983-5990.
33. Ren D, Yi H, Wang W, Ma X,. The enzymatic degradation and swelling properties of chitosan matrices with different degrees of N-acetylation. Carbohydr Res 2005; 340: 2403-2410.
34. Chesnutt BM, Yuan Y, Buddington K, Haggard WO, Bumgardner JD,. Composite chitosan/nano-hydroxyapatite scaffolds induce osteocalcin production by osteoblasts in vitro and support bone formation in vivo. Tissue Eng Part A 2009; 15: 2571-2579.
35. Hou J, Wang J, Cao L, Qian X, Xing W, Lu J, Liu C,. Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres composite scaffold in a rabbit model. Biomed Mater 2012; 7: 035002.
36. Patil S, Babbar A, Mathur R, Mishra A, Sawant K,. Mucoadhesive chitosan microspheres of carvedilol for nasal administration. J Drug Target 2010; 18: 321-31.
37. Malaekeh-Nikouei B, Sajadi Tabassi SA, Jaafari MR,. Preparation, characterization, and mucoadhesive properties of chitosan-coated microspheres encapsulated with cyclosporine A. Drug Dev Ind Pharm 2008; 34: 492-498
38. Wang LY, Ma GH, Su ZG,. Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug. J Control Release 2005; 106: 62-75.
39. Freier T, Koh HS, Kazazian K, Shoichet MS,. Controlling cell adhesion and degradation of chitosan films by N-acetylation. Biomaterials 2005; 26: 5872-5878.
40. Lieder R, Darai M, Thor MB, Ng CH, Einarsson JM, Gudmundsson S, Helgason B, Gaware VS, Másson M, Gíslason J, Orlygsson G, Sigurjónsson OE., In vitro bioactivity of different degree of deacetylation chitosan, a potential coating material for titanium implants. J Biomed Mater Res A 2012 Jul 6. doi: 10.1002/jbm.a.34283. [Epub ahead of print]
41. Mao JS, Cui YL, Wang XH, Sun Y, Ying YJ, Zhao HM, De Yao K,. A preliminary study on chitosan and gelatin polyelectrolyte complex cytocompatability by cell cycle and apoptosis analysis. Biomaterials 2004; 25: 3973-3981.
42. Jayasuriya AC, Bhat A,. Optimization of scaled-up chitosan microparticles for bone regeneration. Biomed Mater 2009; 4: 055006.
43. Jayasuriya AC, Bhat A,. Fabrication and characterization of novel hybrid organic/inorganic microparticles to apply in bone regeneration. J Biomed Mater Res A 2010; 92: 1280-1288.
44. Jayasuriya AC, Bhat A,. Mesenchymal stem cell function on hybrid organic/inorganic microparticles in vitro. J Tissue Eng Regen Med 2010; 4: 340-348.
45. Jayasuriya AC, Mauch KJ, Ebraheim NA. Fabrication and characterization of injectable biomaterials for biomedical applications. Adv Mat Res 2012; 383: 4065-4069.
46. Bhat A, Dreifke M, Gomez C, Kandimalla Y, Ebraheim NA, Jayasuriya AC,. Evaluation of cross-linked chitosan microparticles for bone regeneration. J Tissue Eng Regen Med 2010; 4: 532-542.
47. Jayasuriya AC, Mauch KJ, In vitro degradation behavior of chitosan based hybrid microparticles. J Biomed Sci Eng 2011; 4: 383-390.
48. Cruz DM, Escobar Ivirico JL, Gomes MM, Gomez Ribelles JL, Salmeron Sanchez M, Reis RL, Mano JF,. Chitosan microparticles as injectable scaffolds for tissue engineering. J Tiss Eng Regen Med 2008; 2: 378-380.
49. Krebs MD, Salter E, Chen E, Sutter KA, Alsberg E,. Calcium phosphate-DNA nanoparticle gene delivery from alginate hydrogels induces in vivo osteogenesis. J Biomed Mater Res A 2010; 92: 1131-1138.
50. Hou T, Xu J, Li Q, Feng J, Zen L,. In vitro evaluation of a fibrin gel antibiotic delivery system containing mesenchymal stem cells and vancomycin alginate beads for treating bone infections and facilitating bone formation. Osteoarthritis Cartilage 2009; 17, 1377-1384.
51. Lee KY, Alsberg E, Mooney DJ,. Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering. J Biomed Mater Res 2001; 56: 228-233.
52. Smith AM, Harris JJ, Shelton RM, Perrie Y., 3D culture of bone-derived cells immobilised in alginate following light-triggered gelation. J Control Release 2007; 119: 94-101.
53. Barralet JE, Wang L, Lawson M, Triffitt JT, Cooper PR, Shelton RM,. Comparison of bone marrow cells growth on 2D and 3D alginate hydrogels. J Mater Sci Mater Med 2005; 16: 515-519.
54. Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, García AJ, Guldberg RE,. Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 2011; 32: 5241-5251.
55. Zhao L, Weir MD, Xu HH,. An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering. Biomaterials 2010; 31: 6502-6510.
56. Zhou H, Xu HH,. The fast release of stem cells from alginate-fibrin microbeads in injectable scaffolds for bone tissue engineering. Biomaterials 2011; 32: 7503-7513.
57. Place ES, Rojo L, Gentleman E, Sardinha JP, Stevens MM,. Strontium- and zinc-alginate hydrogels for bone tissue engineering. Tissue Eng Part A 2011; 17: 2713-2722.
58. Kim D, Monaco E, Maki A, de Lima AS, Kong HJ, Hurley WL, Wheeler MB,. Morphologic and transcriptomic comparison of adipose-and bone-marrow-derived porcine stem cells cultured in alginate hydrogels. Cell Tissue Res 2010; 341: 359-370.
59. Wang Z, Goh J, Das De S, Ge Z, Ouyang H, Chong JS, Low SL, Lee EH. Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in a rabbit model. Tissue Eng 2006; 12: 1753-1761.
60. Mo XT, Guo SC, Xie HQ, Deng L, Zhi W, Xiang Z, Li XQ, Yang ZM,. Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes regulate the expression of cartilaginous and osseous phenotype in alginate constructs. Bone 2009; 45: 42-51.
61. Tan R, She Z, Wang M, Yu X, Jin H, Feng Q,. Repair of rat calvarial bone defects by controlled release of rhBMP-2 from an injectable bone regeneration composite. J Tissue Eng Regen Med 2011. doi: 10.1002/term.463.
62. Vindigni V, Cortivo R, Icobellis L, Abatangelo G, Zavan B,. Hyaluronan benzyl ester as a scaffold for tissue engineering. Int J Mol Sci 2009; 10: 2972-2985.
63. Tenorio DM, Scaletta C, Jaccoud S, Hirt-Burri N, Pioletti DP, Jaques B, Applegate LA,. Human fetal bone cells in delivery systems for bone engineering. J Tissue Eng Regen Med 2011; 5: 806-814.
64. Kim J, Kim IS, Cho TH, Lee KB, Hwang SJ, Tae G, Noh I, Lee SH, Park Y, Sun K,. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 2007; 28: 1830-1837.
65. Radice M, Brun P, Cortivo R, Scapinelli R, Battaliard C, Abatangelo G,. Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res 2000; 50: 101-109.
66. Toole BP,. Hyaluronan in morphogenesis. Semin Cell Dev Biol 2001; 12: 79-87.
67. Docherty-Skogh AC, Bergman K, Waern MJ, Ekman S, Hultenby K, Ossipov D, Hilborn J, Bowden T, Engstrandt T,. Bone morphogenetic protein-2 delivered by hyaluronan-based hydrogel induces massive bone formation and healing of cranial defects in minipigs. Plast Reconstr Surg 2010; 125: 1383-1392.
68. Varghese OP, Sun W, Hilborn J, Ossipov DA,. In situ cross-linkable high molecular weight hyaluronan-bisphosphonate conjugate for localized delivery and cell-specific targeting: a hydrogel linked prodrug approach. J Am Chem Soc 2009; 131: 8781-8783.
69. Varghese OP, Kisiel M, Martínez-Sanz E, Ossipov DA, Hilborn J,. Synthesis of guanidinium-modified hyaluronic Acid hydrogel. Macromol Rapid Commun 2010; 31: 1175-1180.
70. Bergman K, Engstrand T, Hilborn J, Ossipov D, Piskounova S, Bowden T,. Injectable cell-free template for bone-tissue formation. J Biomed Mater Res A 2009; 91: 1111-1118.
71. Eckardt H, Christensen KS, Lind M, Hansen ES, Hall DW, Hvid I,. Recombinant human bone morphogenetic protein 2 enhances bone healing in an experimental model of fractures at risk of non-union. Injury 2005; 36: 489-494.
72. Matsuno H, Yudoh K, Hashimoto M, Himeda Y, Miyoshi T, Yoshida K, Kano S,. A new antibacterial carrier of hyaluronic acid gel. J Orthop Sci 2006; 11: 497-504.
73. Jang CH, Park H, Cho YB, Song CH,. Mastoid obliteration using a hyaluronic acid gel to deliver a mesenchymal stem cells-loaded demineralized bone matrix: an experimental study. Int J Pediatr Otorhinolaryngol 2008; 72: 1627-1632.
74. Gyawali D, Nair P, Zhang Y, Tran RT, Zhang Samchukov, CM, Makarov M, Kim HKW, Yang J., Citric acid-derived in situ crosslinkable biodegradable polymers for cell delivery. Biomaterials 2010; 31: 9092-9105.
75. Lynn AD, Kyriakides TR, Bryant SJ,. Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mat Res 2009; 93: 941-953.
76. Betz MW, Yeatts AB, Richbourg WJ, Caccamese JF, Coletti DP, Falco EE, Fisher JP,. Macroporous hydrogels upregulate osteogenic signal expression and promote bone regeneration. Biomacromolecules 2010; 11: 1160-1168.
77. Kaihara S, Matsumura S, Fisher JP,. Cellular responses to degradable cyclic acetal modified PEG hydrogels. J Biomed Mat Res 2008; 90: 863-873.
78. Briggs T, Treiser MD, Holmes PF, Kohn J, Moghe PV, Arinzeh TL,. Osteogenic differentiation of human mesenchymal stem cells on poly(ethylene glycol)-variant biomaterials. J Biomed Mater Res A 2009; 91: 975-984.
79. Killion JA, Geever LM, Devine DM, Kennedy JE, Higginbotham CL,. Mechanical properties and thermal behaviour of PEGDMA hydrogels for potential bone regeneration application. J Mech Behav Biomed Mater 2011; 4: 1219-1227.
80. Cai L, Wang K, Wang S,. Poly(ethylene glycol)-grafted poly(propylene fumarate) networks and parabolic dependence of MC3T3 cell behavior on the network composition. Biomaterials 2010; 31: 4457-4466.
81. Kaihara S, Matsumura S, Fisher JP,. Synthesis and characterization of cyclic acetal based degradable hydrogels. Euro J Pharm and Biopharm 2008; 68: 67-73.
82. Nicodemus GD, Villanueva I, Bryant SJ,. Mechanical stimulation of TMJ condylar chondrocytes encapsulated in PEG hydrogels. J Biomed Mat Res 2007; 83: 323-331.
83. Shin H, Jo S, Mikos AG,. Modulation of marrow stromal osteoblast adhesion on biomimetic oligo[poly(ethylene glycol) fumarate] hydrogels modified with Arg-Gly-Asp peptides and a poly(ethylene glycol) spacer. J Biomed Mater Res 2002; 61: 169-179.
84. Steinmetz NJ, Bryant SJ,. The effects of intermittent dynamic loading on chondrogenic and osteogenic differentiation of human marrow stromal cells encapsulated in RGD-modified poly(ethylene glycol) hydrogels. Acta Biomater 2011; 7: 3829-3840.
85. Kim J, Hefferan TE, Yaszemski MJ, Lu L,. Potential of hydrogels based on poly(ethylene glycol) and sebacic acid as orthopedic tissue engineering scaffolds. Tissue Eng Part A 2009; 15: 2299-2307.
86. Doroski DM, Levenston ME, Temenoff JS,. Cyclic tensile culture promotes fibroblastic differentiation of marrow stromal cells encapsulated in poly(ethylene glycol)-based hydrogels. Tissue Eng Part A 2010; 16: 3457-3466.
87. Huh KM, Cho YW, Park K,. PLGA-PEG block copolymers for drug formulations. Drug dev Deliv 2003; 3.
88. Lee PY, Cobain E, Huard J, Huang L,. Thermosensitive hydrogel PEG-PLGA-PEG enhances engraftment of muscle-derived stem cells and promotes healing in diabetic wound. Mol Ther 2007; 15: 1189-1194.
89. Chung YM, Simmons KL, Gutowska A, Jeong B,. Sol-gel transition temperature of PLGA-g-PEG aqueous solutions. Biomacromolecules 2002; 3: 511-516.
90. Tarasevich BJ, Gutowska A, Li XS, Jeong B-M,. The effect of polymer composition on the gelation behavior of PLGA-g-PEG biodegradable thermoreversible gels. J Biomed Mater Res 2009; 89: 248-254.
91. Yu L, Zhang Z, Ding J,. Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers. Biomacromolecules. 2011; 12: 1290-1297.
92. Jeong B, Han Bae Y, Kim, SW,. In situ gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions and degradation thereof. J Biomater Res 2000; 50: 171-177.
93. Ni PY, Fan M, Qian ZY, Luo JC, Gong CY, Fu SZ, Shi S, Luo F, Yang ZM,. Synthesis and characterization of injectable, thermosensitive, and biocompatible acellular bone matrix/poly(ethylene glycol)-poly (ε-caprolactone)- poly(ethylene glycol) hydrogel composite. J Biomed Mater Res A 2012; 100: 171-179.
94. Fu S, Guo G, Gong C, Zeng S, Liang H, Luo F, Zhang X, Zhao X, Wei Y, Qian Z,. Injectable biodegradable thermosensitive hydrogel composite for orthopedic tissue engineering, Part 1: preparation and characterization of n-hydroxyapatite/poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) hydrogel nanocomposites. J Phys Chem B 2009; 113: 16518-16525.
95. Fu S, Ni P, Wang B, Chu B, Zheng L, Luo F, Luo J, Qian Z,. Injectable PEG-PCL-PEG/collagen/HA thermosensitive hydrogel composite for guiding bone regeneration. Biomaterials 2012; 33: 4801-4809.
96. Gallet G, Carroccio S, Rizzarelli P, Karlsson S,. A phenomenological psychological study of decision and choice. Polymer 2002; 43: 1081-1094.
97. Bengt Erlandsson,. Stability-indicating changes in poloxamers: the degradation of ethylene oxide-propylene oxide block copolymers at 25 and 40 deg C. Polym Degrad Stab 2002; 78: 571-575.