PDF
Abstract
Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.
Biomaterials: Dual-layered hydrogel aids bone and cartilage repair
A dual-layered polymer hydrogel could help to treat injuries to cartilage and bone. Yunfeng Lin and colleagues from Sichuan University in Chengdu, China, developed a relatively simple recipe for synthesizing a biphasic hydrogel with an upper layer that mirrors the properties of articular cartilage and a lower one that resembles subchondral bone. In cell culture, the upper and lower layers maintained the viability of cartilage cells and bone-forming osteoblast cells, respectively. The hydrogel broke down with minimal inflammation when implanted inside rats, demonstrating its biodegradability and biocompatibility. Experiments in rabbits with leg injuries showed that the hydrogel served as a temporary scaffold to enhance regeneration before being replaced by native tissue. The researchers suggest that this or similar dual-layered hydrogels could be used in the future application of bone and cartilage tissue engineering to people.
Cite this article
Download citation ▾
Jinfeng Liao, Taoran Tian, Sirong Shi, Xueping Xie, Quanquan Ma, Guo Li, Yunfeng Lin.
The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair.
Bone Research, 2017, 5(1): 17018 DOI:10.1038/boneres.2017.18
| [1] |
Huang BJ, Hu JC, Athanasiou KA. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials, 2016, 98: 1-22
|
| [2] |
Armstrong JPK, Shakur R, Horne JP et al. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue. Nat Commun, 2015, 6: 7405
|
| [3] |
Huey DJ, Hu JC, Athanasiou KA. Unlike bone, cartilage regeneration remains elusive. Science, 2012, 338: 917-921
|
| [4] |
Levingstone TJ, Ramesh A, Brady RT et al. Cell-free multi-layered collagen-based scaffolds demonstrate layer specific regeneration of functional osteochondral tissue in caprine joints. Biomaterials, 2016, 87: 69-81
|
| [5] |
Lee P, Tran K, Zhou G et al. Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds. Soft Matter, 2015, 11: 7648-7655
|
| [6] |
Nonoyama T, Wada S, Kiyama R et al. Double-network hydrogels strongly bondable to bones by spontaneous osteogenesis penetration. Adv Mater, 2016, 28: 6740-6745
|
| [7] |
Gong T, Jing X, Liao J et al. Nanomaterials and bone regeneration. Bone Res, 2015, 3: 15029
|
| [8] |
Meng Q, Man Z, Dai L et al. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration. Sci Rep, 2015, 5: 17802
|
| [9] |
Choi B, Kim S, Lin B et al. Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering. ACS Appl Mater Interfaces, 2014, 6: 20110-20121
|
| [10] |
Huebsch N, Arany PR, Mao AS et al. Harnessing traction-mediated manipulation of the cell-matrix interface to control stem cell fate. Nat Mater, 2010, 9: 518-526
|
| [11] |
Zouani OF, Kalisky J, Ibarboure E et al. Effect of BMP-2 from matrices of different stiffnesses for the modulation of stem cell fate. Biomaterials, 2013, 34: 2157-2166
|
| [12] |
Wang L-S, Du C, Toh WS et al. Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties. Biomaterials, 2014, 35: 2207-2217
|
| [13] |
Camarero-Espinosa S, Rothen-Rutishauser B, Weder CE et al. Directed cell growth in multi-zonal scaffolds for cartilage tissue engineering. Biomaterials, 2016, 74: 42-52
|
| [14] |
Jia S, Zhang T, Xiong Z et al. In vivo evaluation of a novel oriented scaffold-BMSC construct for enhancing full-thickness articular cartilage repair in a rabbit model. PLoS ONE, 2015, 10: e0145667
|
| [15] |
Oh SH, An DB, Kim TH et al. Wide-range stiffness gradient PVA/HA hydrogel to investigate stem cell differentiation behavior. Acta Biomater, 2016, 35: 23-31
|
| [16] |
Nguyen LH, Kudva AK, Saxena NS et al. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials, 2011, 32: 6946-6952
|
| [17] |
Oliveira JM, Rodrigues MT, Silva SS et al. Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials, 2006, 27: 6123-6137
|
| [18] |
Zhang W, Chen J, Tao J et al. The promotion of osteochondral repair by combined intra-articular injection of parathyroid hormone-related protein and implantation of a bi-layer collagen-silk scaffold. Biomaterials, 2013, 34: 6046-6057
|
| [19] |
Zhang S, Chen L, Jiang Y et al. Bi-layer collagen/microporous electrospun nanofiber scaffold improves the osteochondral regeneration. Acta Biomater, 2013, 9: 7236-7247
|
| [20] |
Steele JAM, McCullen SD, Callanan A et al. Combinatorial scaffold morphologies for zonal articular cartilage engineering. Acta Biomater, 2014, 10: 2065-2075
|
| [21] |
Yan LP, Silva-Correia J, Oliveira MB et al. Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater, 2015, 12: 227-241
|
| [22] |
Chen J, Chen H, Li P et al. Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by as patially controlled gene delivery system in bilayered integrated scaffolds. Biomaterials, 2011, 32: 4793-4805
|
| [23] |
Levingstone TJ, Matsiko A, Dickson GR et al. A biomimetic multi-layered collagen-based scaffold for osteochondral repair. Acta Biomater, 2014, 10: 1996-2004
|
| [24] |
Sukarto A, Yu C, Flynn LE et al. Co-delivery of adipose-derived stem cells and growth factor-loaded microspheres in RGD-grafted N-methacrylate glycol chitosan gels for focal chondral repair. Biomacromolecules, 2012, 13: 2490-2502
|
| [25] |
Lam J, Clark EC, Fong ELS et al. Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering. Biomaterials, 2016, 83: 332-346
|
| [26] |
Wang DA, Varghese S, Sharma B et al. Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. Nat Mater, 2007, 6: 385-392
|
| [27] |
Liao J, Qu Y, Chu B et al. Biodegradable CSMA/PECA/grapheme porous hybrid scaffold for cartilage tissue engineering. Sci Rep, 2015, 5: 09879
|
| [28] |
Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26: 5474-5491
|
| [29] |
Visser J, Melchels FPW, Jeon JE et al. Reinforcement of hydrogels using three-dimensionally printed microfibers. Nat Commun, 2015, 6: 6933
|
| [30] |
Shao XX, Hutmacher DW, Ho ST et al. Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits. Biomaterials, 2006, 27: 1071-1080
|
| [31] |
Huang H, Zhang X, Hu X et al. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration. Biomaterials, 2014, 35: 9608-9619
|
| [32] |
Yan S, Wang T, Feng L et al. Injectable in situ self-cross-linking hydrogels based on poly(L-glutamic acid) and alginate for cartilage tissue engineering. Biomacromolecules, 2014, 15: 4495-4508
|
| [33] |
Fu N, Liao J, Lin S et al. PCL-PEG-PCL film promotes cartilage regeneration in vivo. Cell Prolif, 2016, 49: 729-739
|
| [34] |
Lin Y, Tian W, Chen X et al. Expression of exogenous or endogenous green fluorescent protein in adipose tissue-derived stromal cells during chondrogenic differentiation. Mol Cell Biochem, 2005, 277: 181-190
|
| [35] |
Griffith M, Osborne R, Munger R et al. Functional human corneal equivalents constructed from cell lines. Science, 1999, 286: 2169-2172
|
| [36] |
Soletti L, Hong Y, Guan J et al. A bilayered elastomeric scaffold for tissue engineering of small diameter vascular grafts. Acta Biomater, 2010, 6: 110-122
|
| [37] |
Zhang T, Xie J, Sun K et al. Physiological Oxygen Tension Modulates the Soluble Growth Factor Profile after Crosstalk between Chondrocytes and Osteoblasts. Cell Prolif, 2016, 49: 122-133
|
| [38] |
Shi S, Xie J, Zhong J et al. Effects of low oxygen tension on gene profile of soluble growth factors in co-cultured adipose-derived stromal cells and chondrocytes. Cell Prolif, 2016, 49: 341-351
|