Vật liệu sinh học từ Alginate cho ứng dụng trong y học tái sinh

Materials - Tập 6 Số 4 - Trang 1285-1309
Jinchen Sun1, Huaping Tan2
1School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. [email protected].
2School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. [email protected].

Tóm tắt

Alginate là một polyme polysaccharide tự nhiên thể hiện tính tương thích sinh học và khả năng phân huỷ sinh học xuất sắc, có nhiều ứng dụng khác nhau trong lĩnh vực y sinh học. Alginate có thể được chế biến dễ dàng thành các vật liệu giá thể ba chiều có thể áp dụng như hydrogel, vi cầu, vi nang, bọt biển, bọt xốp và sợi. Vật liệu sinh học dựa trên alginate có thể được sử dụng làm hệ thống dẫn truyền thuốc và là phương tiện mang tế bào trong kỹ thuật mô. Alginate có thể dễ dàng biến đổi thông qua các phản ứng hoá học và vật lý để thu được các dẫn xuất có cấu trúc, tính chất, chức năng và ứng dụng khác nhau. Việc điều chỉnh cấu trúc và tính chất như khả năng phân hủy sinh học, độ bền cơ học, tính chất gel hóa và ái lực tế bào có thể đạt được thông qua kết hợp với các vật liệu sinh học khác, cố định hóa các ligand cụ thể như peptide và phân tử đường, và liên kết chéo vật lý hoặc hoá học. Bài tổng quan này tập trung vào những tiến bộ gần đây trong việc sử dụng alginate và các dẫn xuất của nó trong lĩnh vực ứng dụng y học, bao gồm chữa lành vết thương, phục hồi sụn, tái tạo xương và dẫn truyền thuốc, những điều này có tiềm năng trong ứng dụng tái tạo mô.

Từ khóa

#alginate #vật liệu sinh học #y học tái sinh #chữa lành vết thương #sửa chữa sụn #tái tạo xương #dẫn truyền thuốc #công nghệ mô.

Tài liệu tham khảo

Lee, 2012, Alginate: Properties and biomedical applications, Prog. Polym. Sci., 37, 106, 10.1016/j.progpolymsci.2011.06.003

Lee, 2007, Polymeric protein delivery systems, Progr. Polym. Sci., 32, 669, 10.1016/j.progpolymsci.2007.04.001

Pawar, 2012, Alginate derivatization: a review of chemistry, properties and applications, Biomaterials, 33, 3279, 10.1016/j.biomaterials.2012.01.007

Tan, 2007, Gelatin/chitosan/hyaluronan ternary complex scaffold containing basic fibroblast growth factor for cartilage tissue engineering, J. Mater. Sci. Mater. Med., 18, 1961, 10.1007/s10856-007-3095-5

Senni, 2011, Marine polysaccharides: A source of bioactive molecules for cell therapy and tissue engineering, Mar. Drugs, 9, 1664, 10.3390/md9091664

Wu, 2009, Covalently immobilized gelatin gradients within three-dimensional porous scaffolds, Chin. Sci. Bull., 54, 3174, 10.1007/s11434-009-0215-2

Narayanan, 2012, Photodegradable iron(III) cross-linked alginate gels, Biomacromolecules, 13, 2465, 10.1021/bm300707a

Grasdalen, 1989, Inhomogeneous polysaccharide ionic gels, Carbohydr. Polym., 10, 31, 10.1016/0144-8617(89)90030-1

Stevens, 2004, A rapid-curing alginate gel system: Utility in periosteum-derived cartilage tissue engineering, Biomaterials, 25, 887, 10.1016/j.biomaterials.2003.07.002

Kuo, 2001, Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties, Biomaterials, 22, 511, 10.1016/S0142-9612(00)00201-5

Bouhadir, 2001, Degradation of partially oxidized alginate and its potential application for tissue engineering, Biotechnol. Prog., 17, 945, 10.1021/bp010070p

Kong, 2004, Controlling degradation of hydrogel via the size of cross-linked junctions, Adv. Mater., 16, 1917, 10.1002/adma.200400014

Balakrishnan, 2005, Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds, Biomaterials, 26, 3941, 10.1016/j.biomaterials.2004.10.005

Gaserod, 1998, Microcapsules of alginate-chitosan I: A quantitative study of the interaction between alginate and chitosan, Biomaterials, 19, 1815, 10.1016/S0142-9612(98)00073-8

Rowley, 1999, Alginate hydrogels as synthetic extracellular matrix materials, Biomaterials, 20, 45, 10.1016/S0142-9612(98)00107-0

Lee, 2001, Hydrogels for tissue engineering, Chem. Rev., 101, 1869, 10.1021/cr000108x

Tan, 2010, Injectable, biodegradable hydrogels for tissue engineering applications, Materials, 3, 1746, 10.3390/ma3031746

Tememoff, 2000, Injectable biodegradable materials for orthopedic tissue engineering, Biomaterials, 21, 2405, 10.1016/S0142-9612(00)00108-3

Hou, 2004, Injectable scaffolds for tissue regeneration, J. Mater. Chem., 14, 1915, 10.1039/b401791a

Drury, 2003, Hydrogels for tissue engineering: scaffold design variables and applications, Biomaterials, 24, 4337, 10.1016/S0142-9612(03)00340-5

Nuttelman, 2008, Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering, Prog. Polym. Sci., 33, 167, 10.1016/j.progpolymsci.2007.09.006

Brandl, 2007, Rational design of hydrogels for tissue engineering: Impact of physical factors on cell behavior, Biomaterials, 28, 134, 10.1016/j.biomaterials.2006.09.017

Rehfeldt, 2007, Cell responses to the mechanochemical microenvironment—Implications for regenerative medicine and drug delivery, Adv. Drug Deliv. Rev., 59, 1329, 10.1016/j.addr.2007.08.007

Nicodemus, 2008, Cell encapsulation in biodegradable hydrogels for tissue Engineering applications, Tissue Eng., 14, 149, 10.1089/ten.teb.2007.0332

Varghese, 2006, Hydrogels for musculoskeletal tissue engineering, Adv. Polym. Sci., 203, 95, 10.1007/12_072

Tan, 2009, Novel multi-arm PEG-based hydrogels for tissue engineering, J. Biomed. Mater. Res. A, 92, 979

Tan, 2012, Biological self-assembly of injectable hydrogel as cell scaffold via specific nucleobase pairing, Chem. Commun., 48, 10289, 10.1039/c2cc35449g

Tan, 2011, Direct synthesis of biodegradable polysaccharide derivative hydrogels through aqueous Diels-Alder chemistry, Macromol. Rapid Commun., 32, 905, 10.1002/marc.201100125

Donati, 2005, New hypothesis on the role of alternating sequences in calcium-alginate gels, Biomacromolecules, 6, 1031, 10.1021/bm049306e

Crow, 2006, Release of bovine serum albumin from a hydrogel-cored biodegradable polymer fiber, Biopolymers, 81, 419, 10.1002/bip.20442

Ruvinov, 2010, The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hind limb ischemia model, Biomaterials, 31, 4573, 10.1016/j.biomaterials.2010.02.026

Gan, 2009, In situ gelation of P(NIPAM-HEMA) microgel dispersion and its applications as injectable 3D cell scaffold, Biomacromolecules, 10, 1410, 10.1021/bm900022m

Kim, 2002, Rapid temperature/pH response of porous alginate-g-poly(N-isopropylacrylamide) hydrogels, Polymer, 43, 7549, 10.1016/S0032-3861(02)00675-4

Lee, 2004, Temperature/pH-sensitive comb-type graft hydrogels composed of chitosan and poly(N-isopropylacrylamide), J. Appl. Polym. Sci., 92, 2612, 10.1002/app.20265

Lee, 2004, Synthesis and characterization of thermosensitive chitosan copolymer as a novel biomaterial, J. Biomed. Mater. Res., 15, 1065

Wang, 2009, Cell adhesion and accelerated detachment on the surface of temperature-sensitive chitosan and poly(N-isopropylacrylamide) hydrogels, J. Mater. Sci. Mater. Med., 20, 583, 10.1007/s10856-008-3593-0

Chen, 2006, Thermo-responsive chitosan-graft-poly(N-isopropylacrylamide) injectable hydrogel for cultivation of chondrocytes and meniscus cells, Macromol. Biosci., 6, 1026, 10.1002/mabi.200600142

Cho, 2004, Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer, Biomaterials, 25, 5743, 10.1016/j.biomaterials.2004.01.051

Ha, 2006, Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors, Macromol. Res., 14, 87, 10.1007/BF03219073

Ibusuki, 2003, Tissue-engineered cartilage using an injectable and in situ gelable thermoresponsive gelatin: fabrication and in vitro performance, Tissue Eng., 9, 371, 10.1089/107632703764664846

Tan, 2009, Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering, Biomaterials, 30, 6844, 10.1016/j.biomaterials.2009.08.058

Abdi, 2012, In vitro study of a blended hydrogel composed of Pluronic F-127-alginate-hyaluronic acid for its cell injection application, J. Tissue Eng. Regen. Med., 9, 1, 10.1007/s13770-012-0001-0

Lee, 2003, Hydrogel formation via cell crosslinking, Adv. Mater., 15, 1828, 10.1002/adma.200305406

Lehenkari, 1999, Single integrin molecule adhesion forces in intact cells measured by atomic force microscopy, Biochem. Bio-phys. Res. Commun., 259, 645, 10.1006/bbrc.1999.0827

Koo, 2002, Coregulation of cell adhesion by nanoscale RGD organization and mechanical stimulus, J. Cell Sci., 115, 1423, 10.1242/jcs.115.7.1423

Schmedlen, 2002, Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering, Biomaterials, 23, 4325, 10.1016/S0142-9612(02)00177-1

Hu, 2008, Photoinitiating polymerization to prepare biocompatible chitosan hydrogels, J. Appl. Polym. Sci., 110, 1059, 10.1002/app.28704

Ifkovits, 2007, Review: photopolymerizable and degradable biomaterials for tissue engineering applications, Tissue Eng., 13, 2369, 10.1089/ten.2007.0093

Varghese, 2008, Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells, Matrix Biology, 27, 12, 10.1016/j.matbio.2007.07.002

Park, 2003, Photopolymerized hyaluronic acid-based hydrogels and interpenetrating networks, Biomaterials, 24, 893, 10.1016/S0142-9612(02)00420-9

DeLong, 2005, Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration, J. Control. Rel., 109, 139, 10.1016/j.jconrel.2005.09.020

Garagorri, 2008, Keratocyte behavior in three-dimensional photopolymerizable poly(ethylene glycol) hydrogels, Acta Biomater., 4, 1139, 10.1016/j.actbio.2008.05.007

Bryant, 2004, Crosslinking density influences the morphology of chondrocytes photoencapsulated in PEG hydrogels during the application of compressive strain, J. Orthop. Res., 22, 1143, 10.1016/j.orthres.2004.02.001

Rice, 2004, Encapsulating chondrocytes in copolymer gels: Bimodal degradation kinetics influence cell phenotype and extracellular matrix development, J. Biomed. Mater. Res., 70A, 560, 10.1002/jbm.a.30106

Bryant, 2004, Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: Engineering gel structural changes to facilitate cartilaginous tissue production, Biotechnol. Bioeng., 86, 747, 10.1002/bit.20160

Peter, 2000, Marrow stormal osteoblast function on a poly(propylene fumarate)/β-tricalcium phosphate biodegradable orthopaedic composite, Biomaterials, 21, 1207, 10.1016/S0142-9612(99)00254-9

He, 2000, Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate, Biomaterials, 21, 2389, 10.1016/S0142-9612(00)00106-X

Temenoff, 2004, In vitro osetogenic differentiation of marrow stromal cells encapsulated in biodegradable hydrogels, J. Biomed. Mater. Res., 70A, 235, 10.1002/jbm.a.30064

Cha, 2011, Integrative design of a poly(ethylene glycol)-poly(propylene glycol)-alginate hydrogel to control three dimensional biomineralization, Biomaterials, 32, 2695, 10.1016/j.biomaterials.2010.12.038

Balakrishnan, 2005, Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin, Biomaterials, 26, 6335, 10.1016/j.biomaterials.2005.04.012

Dahlmann, 2013, Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering, Biomaterials, 34, 940, 10.1016/j.biomaterials.2012.10.008

Boontheekul, 2005, Controlling alginate gels degradation utilizing partial oxidation and bimodal molecular weight distribution, Biomaterials, 26, 2455, 10.1016/j.biomaterials.2004.06.044

Tan, 2009, Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for cartilage tissue engineering, Biomaterials, 30, 2499, 10.1016/j.biomaterials.2008.12.080

Krause, 2012, Bioorthogonal metal-free click-ligation of cRGD-pentapeptide to alginate, Org. Biomol. Chem., 10, 5547, 10.1039/c2ob25604e

Tan, 2012, Injectable in situ forming glucose-responsive dextran-based hydrogels to deliver adipogenic factor for adipose tissue engineering, J. Appl. Polym. Sci., 126, E180, 10.1002/app.36737

Tan, 2011, Controlled gelation and degradation rates of injectable hyaluronic acid-based hydrogels through a double crosslinking strategy, J. Tissue Eng. Regen. Med., 5, 790, 10.1002/term.378

Tan, 2010, Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for adipose tissue regeneration, Organogenesis, 6, 173, 10.4161/org.6.3.12037

Springer, 2000, Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor, J. Gene Med., 2, 279, 10.1002/1521-2254(200007/08)2:4<279::AID-JGM114>3.0.CO;2-8

Tan, 2009, RGD modified PLGA/gelatin microspheres as microcarriers for chondrocyte delivery, J. Biomed. Mater. Res., 91B, 228, 10.1002/jbm.b.31394

Patil, 2008, Mucoadhesive microspheres: a promising tool in drug delivery, Curr. Drug Deliv., 5, 312, 10.2174/156720108785914970

Basmanav, 2008, Sequential growth factor delivery from complexed microspheres for bone tissue engineering, Biomaterials, 29, 4195, 10.1016/j.biomaterials.2008.07.017

Chang, 1998, Pharmaceutical and therapeutic applications of artificial cells including microencapsulation, Eur. J. Pharm. Biopharm., 45, 3, 10.1016/S0939-6411(97)00117-3

Serra, M., Correia, C., Malpique, R., Brito, C., Jensen, J., Bjorquist, P., Carrondo, M.J., and Alves, P.M. (2011). Microencapsulation technology: A powerful tool for integrating expansion and cryopreservation of human embryonic stem cells. PLoS One, 6.

Kong, 2003, Designing alginate hydrogels to maintain viability of immobilized cells, Biomaterials, 24, 4023, 10.1016/S0142-9612(03)00295-3

Man, 2012, Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived stem cell laden alginate microspheres, Biomaterials, 33, 8802, 10.1016/j.biomaterials.2012.08.054

Yu, 2010, The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat, Biomaterials, 31, 7012, 10.1016/j.biomaterials.2010.05.078

Freiberg, 2004, Polymer microspheres for controlled drug release, Int. J. Pharm., 282, 1, 10.1016/j.ijpharm.2004.04.013

Chen, 2006, Alginate—Whey protein granular microspheres as oral delivery vehicles for bioactive compounds, Biomaterials, 27, 4646, 10.1016/j.biomaterials.2006.04.037

Liu, 2012, Fast-degradable microbeads encapsulating human umbilical cord stem cells in alginate for muscle tissue engineering, Tissue Eng. Part A, 18, 2303, 10.1089/ten.tea.2011.0658

Huang, 2012, Microenvironment of alginate-based microcapsules for cell culture and tissue engineering, J. Biosci. Bioeng., 114, 1, 10.1016/j.jbiosc.2012.02.024

Yao, R., Zhang, R., Luan, J., and Lin, F. (2012). Alginate and alginate/gelatin microspheres for human adipose-derived stem cell encapsulation and differentiation. Biofabrication, 4.

Xie, 2012, Viscoelastic properties of mineralized alginate hydrogel beads, J. Mater. Sci. Mater. Med., 23, 1619, 10.1007/s10856-012-4655-x

Zheng, H., Tian, W., Yan, H., Yue, L., Zhang, Y., Han, F., Chen, X., and Li, Y. (2012). Rotary culture promotes the proliferation of MCF-7 cells encapsulated in three-dimensional collagen-alginate hydrogels via activation of the ERK1/2-MAPK pathway. Biomed. Mater., 7.

Wang, 2011, A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology, Biomaterials, 32, 7118, 10.1016/j.biomaterials.2011.06.018

Tan, 2010, The design of biodegradable microcarriers for induced cell aggregation, Macromol. Biosci., 10, 156, 10.1002/mabi.200900160

Bian, 2011, Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vitro, Biomaterials, 32, 6425, 10.1016/j.biomaterials.2011.05.033

Soran, 2012, Chitosan scaffolds with BMP-6 loaded alginate microspheres for periodontal tissue engineering, J. Microencapsul., 29, 770, 10.3109/02652048.2012.686531

Tan, 2009, Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering, Acta Biomater., 5, 328, 10.1016/j.actbio.2008.07.030

Tan, 2012, Heparin interacting protein mediated assembly of nano-fibrous hydrogel scaffolds for guided stem cell differentiation, Macromol. Biosci., 12, 621, 10.1002/mabi.201100502

Petite, 2000, Tissue-engineered bone regeneration, Nat. Biotechnol., 18, 959, 10.1038/79449

Kuo, 2012, TATVHL peptide-grafted alginate/poly(γ-glutamic acid) scaffolds with inverted colloidal crystal topology for neuronal differentiation of iPS cells, Biomaterials, 33, 8955, 10.1016/j.biomaterials.2012.08.073

Yang, 2001, The design of scaffolds for use in tissue engineering. Part I: Traditional factors, Tissue Eng., 7, 679, 10.1089/107632701753337645

Becker, 2001, Calcium alginate gel: A biocompatible and mechanically stable polymer for endovascular embolization, J. Biomed. Mater. Res., 54, 76, 10.1002/1097-4636(200101)54:1<76::AID-JBM9>3.0.CO;2-V

Wu, 2010, Preparation of aligned porous gelatin scaffolds by unidirectional freeze-drying method, Acta Biomater., 6, 1167, 10.1016/j.actbio.2009.08.041

Bhardwaj, 2010, Electrospinning: A fascinating fiber fabrication technique, Biotechnol. Adv., 28, 325, 10.1016/j.biotechadv.2010.01.004

George, 2010, Hierarchical scaffolds via combined macro- and micro-phase separation, Biomaterials, 31, 641, 10.1016/j.biomaterials.2009.09.094

Salerno, 2009, Design of porous polymeric scaffolds by gas foaming of heterogeneous blends, J. Mater. Sci. Mater. Med., 20, 2043, 10.1007/s10856-009-3767-4

Sapir, 2011, Integration of multiple cell-matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration, Biomaterials, 32, 1838, 10.1016/j.biomaterials.2010.11.008

Florczyk, 2011, Influence of processing parameters on pore structure of 3D porous chitosan-alginate polyelectrolyte complex scaffolds, J. Biomed. Mater. Res. A, 98, 614, 10.1002/jbm.a.33153

Shachar, 2011, The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue engineering, Acta. Biomater., 7, 152, 10.1016/j.actbio.2010.07.034

Kang, 2012, Microfluidic spinning of flat alginate fibers with grooves for cell-aligning scaffolds, Adv. Mater., 24, 4271, 10.1002/adma.201201232

Bonino, 2012, Three-dimensional electrospun alginate nanofiber mats via tailored charge repulsions, Small, 8, 1928, 10.1002/smll.201101791

McCanless, 2012, Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery, J. Mater. Sci. Mater. Med., 23, 1971, 10.1007/s10856-012-4672-9

Spasojevic, 2012, The association between in vitro physicochemical changes and inflammatory responses against alginate based microcapsules, Biomaterials, 33, 5552, 10.1016/j.biomaterials.2012.04.039

Vanacker, 2012, Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells, Biomaterials, 33, 6079, 10.1016/j.biomaterials.2012.05.015

Xu, 2007, Chitosan-hyaluronic acid hybrid film as a novel wound dressing: in vitro and in vitro studies, Polym. Adv. Technol., 18, 869, 10.1002/pat.906

Li, 2012, In situ injectable nano-composite hydrogel composed of curcumin, N,O-carboxymethyl chitosan and oxidized alginate for wound healing application, Int. J. Pharm., 437, 110, 10.1016/j.ijpharm.2012.08.001

Hooper, 2012, The visualisation and speed of kill of wound isolates on a silver alginate dressing, Int. Wound J., 9, 633, 10.1111/j.1742-481X.2012.00927.x

Tan, 2008, Microscale control over collagen gradient on poly(L-lactide) membrane surface for manipulating chondrocyte distribution, Colloids Surf. B Biointerfaces, 67, 210, 10.1016/j.colsurfb.2008.08.019

Tan, 2008, Biomimetic modification of chitosan with covalently grafted lactose and blended heparin for improvement of in vitro cellular interaction, Polym. Adv. Technol., 19, 15, 10.1002/pat.962

Ferretti, 2006, Controlled in vitro degradation of genipin crosslinked poly(ethylene glycol) hydrogels within osteochondral defects, Tissue Eng., 12, 2657, 10.1089/ten.2006.12.2657

Cooper, 2000, Risk factors for the incidence and progression of radiographic knee osteoarthritis, Arthritis Rheum., 43, 995, 10.1002/1529-0131(200005)43:5<995::AID-ANR6>3.0.CO;2-1

Awad, 2004, Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds, Biomaterials, 25, 3211, 10.1016/j.biomaterials.2003.10.045

Paige, 1996, De novo cartilage generation using calcium alginate-chondrocyte constructs, Plast. Reconstr. Surg., 97, 168, 10.1097/00006534-199601000-00027

Lubiatowski, 2006, Articular cartilage repair by means of biodegradable scaffolds, Transplant Proc., 38, 320, 10.1016/j.transproceed.2005.12.012

Chen, 2006, The use of poly(l-lactide) and RGD modified microspheres as cell carriers in a flow intermittency bioreactor for tissue engineering cartilage, Biomaterials, 27, 4453, 10.1016/j.biomaterials.2006.04.011

Henrionnet, 2012, Effect of dynamic loading on MSCs chondrogenic differentiation in3-D alginate culture, Biomed. Mater. Eng., 22, 209

Ma, 2012, Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels, Acta Biomater., 8, 3754, 10.1016/j.actbio.2012.06.028

Coates, 2012, Matrix molecule influence on chondrocyte phenotype and proteoglycan 4 expression by alginate-embedded zonal chondrocytes and mesenchymal stem cells, J. Orthop. Res., 30, 1886, 10.1002/jor.22166

Ghahramanpoor, 2011, A hydrophobically-modified alginate gel system: utility in the repair of articular cartilage defects, J. Mater. Sci. Mater. Med., 22, 2365, 10.1007/s10856-011-4396-2

Reem, 2010, The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFβ1-induced chondrogenesis of human mesenchymal stem cells, Biomaterials, 31, 6746, 10.1016/j.biomaterials.2010.05.025

Wang, 2012, Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold, Biomaterials, 33, 120, 10.1016/j.biomaterials.2011.09.042

Alsberg, 2001, Cell-interactive alginate hydrogels for bone tissue engineering, J. Dent. Res., 80, 2025, 10.1177/00220345010800111501

Abbah, 2006, In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use as injectable bone graft substitute, Biochem. Biophys. Res. Commun., 347, 185, 10.1016/j.bbrc.2006.06.072

Durrieu, 2004, Grafting RGD containing peptides onto hydroxyapatite to promote osteoblastic cells adhesion, J. Mater. Sci. Mater. Med., 15, 779, 10.1023/B:JMSM.0000032818.09569.d9

Grellier, 2009, The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect, Biomaterials, 30, 3271, 10.1016/j.biomaterials.2009.02.033

Jin, 2012, In vitro evaluation of porous hydroxyapatite/chitosan-alginate composite scaffolds for bone tissue engineering, Int. J. Biol. Macromol., 51, 1079, 10.1016/j.ijbiomac.2012.08.027

Rubert, M., Monjo, M., Lyngstadaas, S.P., and Ramis, J.M. (2012). Effect of alginate hydrogel containing polyproline-rich peptides on osteoblast differentiation. Biomed. Mater., 7.

Florczyk, 2012, Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor, J. Biomed. Mater. Res. A, 100, 3408, 10.1002/jbm.a.34288

Tang, 2012, Human embryonic stem cell encapsulation in alginate microbeads in macroporous calcium phosphate cement for bone tissue engineering, Acta Biomater., 8, 3436, 10.1016/j.actbio.2012.05.016

Chen, 2012, Umbilical cord stem cells released from alginate-fibrin microbeads inside macroporous and biofunctionalized calcium phosphate cement for bone regeneration, Acta Biomater., 8, 2297, 10.1016/j.actbio.2012.02.021

Xia, 2012, Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold, J. Biomed. Mater. Res. A, 100, 1044, 10.1002/jbm.a.33232

Brun, 2011, Automated quantitative characterization of alginate/hydroxyapatite bone tissue engineering scaffolds by means of micro-CT image analysis, J. Mater. Sci. Mater. Med., 22, 2617, 10.1007/s10856-011-4447-8

Kolambkar, 2011, An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects, Biomaterials, 32, 65, 10.1016/j.biomaterials.2010.08.074

Nguyen, 2012, Fabrication of oxidized alginate-gelatin-BCP hydrogels and evaluation of the microstructure, material properties and biocompatibility for bone tissue regeneration, J. Biomater. Appl., 27, 311, 10.1177/0885328211404265

Tan, 2012, Injectable nano-hybrid scaffold for biopharmaceuticals delivery and soft tissue engineering, Macromol. Rapid Commun., 33, 2015, 10.1002/marc.201200360

Cao, 2005, pH-Induced self-assembly and capsules of sodium alginate, Biomacromolecules, 6, 2189, 10.1021/bm0501510

Mi, 2003, Chitin/PLGA blend microspheres as a biodegradable drug delivery system: A new delivery system for protein, Biomaterials, 24, 5023, 10.1016/S0142-9612(03)00413-7

Abbah, 2012, In vitro bioactivity of rhBMP-2 delivered with novel polyelectrolyte complexation shells assembled on an alginate microbead core template, J. Control. Rel., 162, 364, 10.1016/j.jconrel.2012.07.027

Zhao, 2006, Assembly of multilayer microcapsules on CaCO3 particles from biocompatible polysaccharides, J. Biomater. Sci. Polym. Ed., 17, 997, 10.1163/156856206778366031

Wong, 2011, Degradation of PEG and non-PEG alginate-chitosan microcapsules in different pH environments, Polym. Degrad. Stabil., 96, 2189, 10.1016/j.polymdegradstab.2011.09.009

Huang, 2011, Light-addressable electrodeposition of cell-encapsulated alginate hydrogels for a cellular microarray using adigital micromirror device, Biomicrofluidics, 5, 34109:1, 10.1063/1.3620420

Li, 2011, Hydrogel droplet microarrays with trapped antibody-functionalized beads for multiplexed protein analysis, Lab Chip., 11, 528, 10.1039/C0LC00291G

Meli, 2012, Influence of a three-dimensional, microarray environment on human Cell culture in drug screening systems, Biomaterials, 33, 9087, 10.1016/j.biomaterials.2012.08.065

Sugaya, 2012, Micropatterning of hydrogels on locally hydrophilized regions on PDMS by stepwise solution dipping and in situ gelation, Langmuir, 28, 14073, 10.1021/la3014706

Liu, 2011, Chitosan-based biomaterials for tissue repair and regeneration, Adv. Polym. Sci., 244, 81, 10.1007/12_2011_118