期刊论文详细信息
Journal of Biological Engineering
TGF-β1 conjugated chitosan collagen hydrogels induce chondrogenic differentiation of human synovium-derived stem cells
Min Lee1  Denis Evseenko2  Bogyu Choi3  Soyon Kim1  Brian Lin3  Jinku Kim4 
[1] Department of Bioengineering, University of California, Los Angeles CA 90095, USA;Department of Orthopaedic Surgery, University of California, Los Angeles CA 90095, USA;Division of Advanced Prosthodontics, University of California, Los Angeles CA 90095, USA;Department of Bio and Chemical Engineering, Hongik University, Sejong 339-701, South Korea
关键词: Chondrogenic differentiation;    Synovium-derived stem cells;    Transforming growth factor;    Type II collagen;    Chitosan hydrogels;   
Others  :  1133597
DOI  :  10.1186/1754-1611-9-1
 received in 2014-10-03, accepted in 2014-12-24,  发布年份 2015
【 摘 要 】

Background

Unlike bone tissue, articular cartilage regeneration has not been very successful and has many challenges ahead. We have previously developed injectable hydrogels using photopolymerizable chitosan (MeGC) that supported growth of chondrocytes. In this study, we demonstrate a biofunctional hydrogel for specific use in cartilage regeneration by conjugating transforming growth factor-β1 (TGF-β1), a well-documented chondrogenic factor, to MeGC hydrogels impregnating type II collagen (Col II), one of the major cartilaginous extracellular matrix (ECM) components.

Results

TGF-β1 was delivered from MeGC hydrogels in a controlled manner with reduced burst release by chemically conjugating the protein to MeGC. The hydrogel system did not compromise viability of encapsulated human synovium-derived mesenchymal stem cells (hSMSCs). Col II impregnation and TGF-β1 delivery significantly enhanced cellular aggregation and deposition of cartilaginous ECM by the encapsulated cells, compared with pure MeGC hydrogels.

Conclusions

This study demonstrates successful engineering of a biofunctional hydrogel with a specific microenvironment tailored to promote chondrogenesis. This hydrogel system can provide promising efficacious therapeutics in the treatment of cartilage defects.

【 授权许可】

   
2015 Kim et al.; licensee BioMed Central.

附件列表
Files Size Format View
Figure 8. 45KB Image download
Figure 7. 90KB Image download
Figure 6. 83KB Image download
Figure 5. 190KB Image download
Figure 4. 119KB Image download
Figure 3. 88KB Image download
Figure 2. 76KB Image download
Figure 1. 150KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】
  • [1]Mehrotra C, Remington PL, Naimi TS, Washington W, Miller R: Trends in total knee replacement surgeries and implications for public health, 1990–2000. Public Health Rep 2005, 120:278-82.
  • [2]Sasso RC, LeHuec JC, Shaffrey C, Grp SIR: Iliac crest bone graft donor site pain after anterior lumbar interbody fusion - A prospective patient satisfaction outcome assessment. J Spinal Disord Tech 2005, 18:S77-81.
  • [3]Sasso RC, LeHuec JC, Shaffrey CI: Iliac crest graft site pain after anterior lumbar interbody fusion: a prospective patient outcome assessment. Neurosurgery 2002, 51:581-–1.
  • [4]Benya PD, Padilla SR, Nimni ME: Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell 1978, 15:1313-21.
  • [5]Diaz-Romero J, Gaillard JP, Grogan SP, Nesic D, Trub T, Mainil-Varlet P: Immunophenotypic analysis of human articular chondrocytes: changes in surface markers associated with cell expansion in monolayer culture. J Cell Physiol 2005, 202:731-42.
  • [6]Ahmed TA, Hincke MT: Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev 2010, 16:305-29.
  • [7]Noth U, Rackwitz L, Heymer A, Weber M, Baumann B, Steinert A, et al.: Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels. J Biomed Mater Res A 2007, 83:626-35.
  • [8]Kim IL, Mauck RL, Burdick JA: Hydrogel design for cartilage tissue engineering: a case study with hyaluronic acid. Biomaterials 2011, 32:8771-82.
  • [9]Noth U, Rackwitz L, Steinert AF, Tuan RS: Cell delivery therapeutics for musculoskeletal regeneration. Adv Drug Deliver Rev 2010, 62:765-83.
  • [10]Hu J, Hou Y, Park H, Choi B, Hou S, Chung A, et al.: Visible light crosslinkable chitosan hydrogels for tissue engineering. Acta Biomater 2012, 8:1730-8.
  • [11]Park H, Choi B, Hu J, Lee M: Injectable chitosan hyaluronic acid hydrogels for cartilage tissue engineering. Acta Biomater 2013, 9:4779-86.
  • [12]Huey DJ, Hu JC, Athanasiou KA: Unlike bone, cartilage regeneration remains elusive. Science 2012, 338:917-21.
  • [13]Natoli RM, Revell CM, Athanasiou KA: Chondroitinase ABC treatment results in greater tensile properties of self-assembled tissue-engineered articular cartilage. Tissue Eng Part A 2009, 15:3119-28.
  • [14]Ha CW, Noh MJ, Choi KB, Lee KH: Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy 2012, 14:247-56.
  • [15]van Lent PL, Blom AB, van der Kraan P, Holthuysen AE, Vitters E, van Rooijen N, et al.: Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Arthritis Rheum 2004, 50:103-11.
  • [16]van Beuningen HM, Glansbeek HL, van der Kraan PM, van den Berg WB: Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage 1998, 6:306-17.
  • [17]McCaffrey TA, Falcone DJ, Vicente D, Du B, Consigli S, Borth W: Protection of transforming growth factor-beta 1 activity by heparin and fucoidan. J Cell Physiol 1994, 159:51-9.
  • [18]Lyon M, Rushton G, Gallagher JT: The interaction of the transforming growth factor-betas with heparin/heparan sulfate is isoform-specific. J Biol Chem 1997, 272:18000-6.
  • [19]McCaffrey TA, Falcone DJ, Borth W, Weksler BB: Alpha 2-macroglobulin/transforming growth factor-beta 1 interactions. Modulation by heparin-like molecules and effects on vascular smooth muscle cells. Ann N Y Acad Sci 1994, 737:368-82.
  • [20]McCaffrey TA, Falcone DJ, Du B: Transforming growth factor-beta 1 is a heparin-binding protein: identification of putative heparin-binding regions and isolation of heparins with varying affinity for TGF-beta 1. J Cell Physiol 1992, 152:430-40.
  • [21]Park JS, Woo DG, Yang HN, Lim HJ, Chung HM, Park KH: Heparin-bound transforming growth factor-beta3 enhances neocartilage formation by rabbit mesenchymal stem cells. Transplantation 2008, 85:589-96.
  • [22]Park JS, Woo DG, Yang HN, Na K, Park KH: Transforming growth factor beta-3 bound with sulfate polysaccharide in synthetic extracellular matrix enhanced the biological activities for neocartilage formation in vivo. J Biomed Mater Res A 2009, 91:408-15.
  • [23]Jung HH, Park K, Han DK: Preparation of TGF-beta1-conjugated biodegradable pluronic F127 hydrogel and its application with adipose-derived stem cells. J Control Release 2010, 147:84-91.
  • [24]Zhang Q, He QF, Zhang TH, Yu XL, Liu Q, Deng FL: Improvement in the delivery system of bone morphogenetic protein-2: a new approach to promote bone formation. Biomed Mater 2012, 7:045002.
  • [25]Bessa PC, Casal M, Reis RL: Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2008, 2:81-96.
  • [26]Zhang L, Yuan T, Guo L, Zhang X: An in vitro study of collagen hydrogel to induce the chondrogenic differentiation of mesenchymal stem cells. J Biomed Mater Res A 2012, 100:2717-25.
  • [27]Pabbruwe MB, Kafienah W, Tarlton JF, Mistry S, Fox DJ, Hollander AP: Repair of meniscal cartilage white zone tears using a stem cell/collagen-scaffold implant. Biomaterials 2010, 31:2583-91.
  • [28]Schneiderbauer MM, Dutton CM, Scully SP: Signaling "cross-talk" between TGF-beta1 and ECM signals in chondrocytic cells. Cell Signal 2004, 16:1133-40.
  • [29]Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T: Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis. Biotechnol Bioeng 2006, 93:1152-63.
  • [30]Warstat K, Meckbach D, Weis-Klemm M, Hack A, Klein G, de Zwart P, et al.: TGF-beta enhances the integrin alpha2beta1-mediated attachment of mesenchymal stem cells to type I collagen. Stem Cells Dev 2010, 19:645-56.
  • [31]Bieniarz C, Husain M, Barnes G, King CA, Welch CJ: Extended length heterobifunctional coupling agents for protein conjugations. Bioconjug Chem 1996, 7:88-95.
  • [32]Lim EH, Sardinha JP, Myers S, Stevens M: Latent transforming growth factor-beta1 functionalised electrospun scaffolds promote human cartilage differentiation: towards an engineered cartilage construct. Archives of plastic surgery 2013, 40:676-86.
  • [33]Zhang H, Migneco F, Lin CY, Hollister SJ: Chemically-conjugated bone morphogenetic protein-2 on three-dimensional polycaprolactone scaffolds stimulates osteogenic activity in bone marrow stromal cells. Tissue Eng Part A 2010, 16:3441-8.
  • [34]He QF, Zhao YN, Chen B, Xiao ZF, Zhang J, Chen L, et al.: Improved cellularization and angiogenesis using collagen scaffolds chemically conjugated with vascular endothelial growth factor. Acta Biomater 2011, 7:1084-93.
  • [35]Huang CYC, Reuben PM, D'Ippolito G, Schiller PC, Cheung HS: Chondrogenesis of human bone marrow-derived mesenchymal stem cells in agarose culture. Anat Rec Part A 2004, 278A:428-36.
  • [36]Bosnakovski D, Mizuno M, Kim G, Ishiguro T, Okumura M, Iwanaga T, et al.: Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells in pellet cultural system. Exp Hematol 2004, 32:502-9.
  • [37]Zhang LM, Su PQ, Xu CX, Yang JL, Yu WH, Huang DS: Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol Lett 2010, 32:1339-46.
  • [38]Cheng NC, Estes BT, Awad HA, Guilak F: Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Eng Part A 2009, 15:231-41.
  • [39]Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F: Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Pt A 2010, 16:523-33.
  • [40]Chung C, Burdick JA: Engineering cartilage tissue. Adv Drug Deliv Rev 2008, 60:243-62.
  • [41]Choi B, Kim S, Lin B, Wu BM, Lee M: Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering. ACS Appl Mater Interfaces 2014, 6:20110-21.
  • [42]Gharibjanian NA, Chua WC, Dhar S, Scholz T, Shibuya TY, Evans GR, et al.: Release kinetics of polymer-bound bone morphogenetic protein-2 and its effects on the osteogenic expression of MC3T3-E1 osteoprecursor cells. Plast Reconstr Surg 2009, 123:1169-77.
  • [43]Lee M, Chen TT, Iruela-Arispe ML, Wu BM, Dunn JC: Modulation of protein delivery from modular polymer scaffolds. Biomaterials 2007, 28:1862-70.
  • [44]Lutolf MP, Weber FE, Schmoekel HG, Schense JC, Kohler T, Muller R, et al.: Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 2003, 21:513-8.
  • [45]Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, et al.: Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 2011, 32:5241-51.
  • [46]Ibusuki S, Halbesma GJ, Randolph MA, Redmond RW, Kochevar IE, Gill TJ: Photochemically cross-linked collagen gels as three-dimensional scaffolds for tissue engineering. Tissue Eng 2007, 13:1995-2001.
  • [47]Amsden BG, Sukarto A, Knight DK, Shapka SN: Methacrylated glycol chitosan as a photopolymerizable biomaterial. Biomacromolecules 2007, 8:3758-66.
  • [48]Nuernberger S, Cyran N, Albrecht C, Redl H, Vecsei V, Marlovits S: The influence of scaffold architecture on chondrocyte distribution and behavior in matrix-associated chondrocyte transplantation grafts. Biomaterials 2011, 32:1032-40.
  • [49]Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F: Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 2004, 25:3211-22.
  • [50]Dehne T, Karlsson C, Ringe J, Sittinger M, Lindahl A: Chondrogenic differentiation potential of osteoarthritic chondrocytes and their possible use in matrix-associated autologous chondrocyte transplantation. Arthritis Res Ther 2009, 11:R133. BioMed Central Full Text
  • [51]Toh WS, Lee EH, Guo XM, Chan JKY, Yeow CH, Choo AB, et al.: Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials 2010, 31:6968-80.
  • [52]Hoffman AS: Hydrogels for biomedical applications. Adv Drug Deliver Rev 2002, 54:3-12.
  • [53]Hutmacher DW: Scaffolds in tissue engineering bone and cartilage. Biomaterials 2000, 21:2529-43.
  • [54]Cushing MC, Anseth KS: Materials science. Hydrogel cell cultures. Science 2007, 316:1133-4.
  • [55]DeLise AM, Fischer L, Tuan RS: Cellular interactions and signaling in cartilage development. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society 2000, 8:309-34.
  • [56]Tacchetti C, Tavella S, Dozin B, Quarto R, Robino G, Cancedda R: Cell condensation in chondrogenic differentiation. Exp Cell Res 1992, 200:26-33.
  • [57]Hall BK, Miyake T: All for one and one for all: condensations and the initiation of skeletal development. Bioessays 2000, 22:138-47.
  • [58]Lu ZF, Doulabi BZ, Wuisman PI, Bank RA, Helder MN: Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells. J Cell Mol Med 2008, 12:2812-22.
  • [59]Jurgens WJ, Lu Z, Zandieh-Doulabi B, Kuik DJ, Ritt MJ, Helder MN: Hyperosmolarity and hypoxia induce chondrogenesis of adipose-derived stem cells in a collagen type 2 hydrogel. J Tissue Eng Regen Med 2012, 6:570-8.
  • [60]Yu SM, Li Y, Kim D: Collagen mimetic peptides: progress towards functional applications. Soft Matter 2011, 7:7927-38.
  • [61]Chun JS, Oh H, Yang S, Park M: Wnt signaling in cartilage development and degeneration. BMB Rep 2008, 41:485-94.
  • [62]Yang G, Yang X: Roles of TGF-b superfamily in the genesis, development and maintenance of cartilage. Yi chuan = Hereditas/Zhongguo yi chuan xue hui bian ji 2008, 30:953-9.
  • [63]Schubert T, Anders S, Neumann E, Scholmerich J, Hofstadter F, Grifka J, et al.: Long-term effects of chondrospheres on cartilage lesions in an autologous chondrocyte implantation model as investigated in the SCID mouse model. Int J Mol Med 2009, 23:455-60.
  • [64]Lewis PB, McCarty LP 3rd, Yao JQ, Williams JM, Kang R, Cole BJ: Fixation of tissue-engineered human neocartilage constructs with human fibrin in a caprine model. J Knee Surg 2009, 22:196-204.
  • [65]Chung C, Burdick JA: Influence of three-dimensional hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis. Tissue Eng Part A 2009, 15:243-54.
  • [66]Fan JB, Park H, Tan S, Lee M: Enhanced osteogenesis of adipose derived stem cells with noggin suppression and delivery of BMP-2. Plos One 2013, 8:e72474.
  • [67]Liu SQ, Tian QA, Hedrick JL, Hui JHP, Ee PLR, Yang YY: Biomimetic hydrogels for chondrogenic differentiation of human mesenchymal stem cells to neocartilage. Biomaterials 2010, 31:7298-307.
  文献评价指标  
  下载次数:98次 浏览次数:21次