Functional Biomolecule Delivery Systems and Bioengineering in Cartilage Regeneration

Author(s): Marta A. Szychlinska, Ugo D'Amora, Silvia Ravalli, Luigi Ambrosio, Michelino Di Rosa, Giuseppe Musumeci*.

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Osteoarthritis (OA) is a common degenerative disease which involves articular cartilage, and leads to total joint disability in the advanced stages. Due to its avascular and aneural nature, damaged cartilage cannot regenerate itself. Stem cell therapy and tissue engineering represent a promising route in OA therapy, in which cooperation of mesenchymal stem cells (MSCs) and three-dimensional (3D) scaffolds contribute to cartilage regeneration. However, this approach still presents some limits such as poor mechanical properties of the engineered cartilage. The natural dynamic environment of the tissue repair process involves a collaboration of several signals expressed in the biological system in response to injury. For this reason, tissue engineering involving exogenous “influencers” such as mechanostimulation and functional biomolecule delivery systems (BDS), represent a promising innovative approach to improve the regeneration process. BDS provide a controlled release of biomolecules able to interact between them and with the injured tissue. Nano-dimensional BDS is the future hope for the design of personalized scaffolds, able to overcome the delivery problems. MSC-derived extracellular vesicles (EVs) represent an attractive alternative to BDS, due to their innate targeting abilities, immunomodulatory potential and biocompatibility. Future advances in cartilage regeneration should focus on multidisciplinary strategies such as modular assembly strategies, EVs, nanotechnology, 3D biomaterials, BDS, mechanobiology aimed at constructing the functional scaffolds for actively targeted biomolecule delivery. The aim of this review is to run through the different approaches adopted for cartilage regeneration, with a special focus on biomaterials, BDS and EVs explored in terms of their delivery potential, healing capabilities and mechanical features.

Keywords: Osteoarthritis, cartilage regeneration, MSCs, mechanical stimulation, biomaterials, biomolecule delivery systems, nanotechnology, extracellular vesicles.

Szychlinska, M.A.; Leonardi, R.; Al-Qahtani, M.; Mobasheri, A.; Musumeci, G. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches. Ann. Phys. Rehabil. Med., 2016, 59(3), 149-156.
Loeser, R.F.; Goldring, S.R.; Scanzello, C.R.; Goldring, M.B. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheum., 2012, 64(6), 1697-1707.
Giunta, S.; Castorina, A.; Marzagalli, R.; Szychlinska, M.A.; Pichler, K.; Mobasheri, A.; Musumeci, G. Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis. Int. J. Mol. Sci., 2015, 16(3), 5922-5944.
Musumeci, G.; Loreto, C.; Castorina, S.; Imbesi, R.; Leonardi, R.; Castrogiovanni, P. New perspectives in the treatment of cartilage damage. Poly(ethylene glycol) diacrylate (PEGDA) scaffold. A review. Ital. J. Anat. Embryol., 2013, 118(2), 204-210.
Szychlinska, M.A.; Stoddart, M.J.; D’Amora, U.; Ambrosio, L.; Alini, M.; Musumeci, G. Mesenchymal stem cell-based cartilage regeneration approach and cell senescence: Can we manipulate cell aging and function? Tissue Eng. Part B Rev., 2017, 23(6), 29-539.
Mollon, B.; Kandel, R.; Chahal, J.; Theodoropoulos, J. The clinical status of cartilage tissue regeneration in humans. Osteoarthritis Cartilage, 2013, 21, 1824-1833.
Ding, C.; Garnero, P.; Cicuttini, F.; Scott, F.; Cooley, H.; Jones, G. Knee cartilage defects: Association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown. Osteoarthritis Cartilage, 2005, 13(3), 198-205.
Musumeci, G.; Castrogiovanni, P.; Mazzone, V.; Szychlinska, M.A.; Castorina, S.; Loreto, C. Histochemistry as a unique approach for investigating normal and osteoarthritic cartilage. Eur. J. Histochem., 2014, 58(2), 107-111.
Alford, J.W.; Cole, B.J. Cartilage restoration, part 1: Basic science, historical perspective, patient evaluation, and treatment options. Am. J. Sports Med., 2005, 33, 295-306.
Jackson, D.W.; Lalor, P.A.; Aberman, H.M.; Simon, T.M. Spontaneous repair of full-thickness defects of articular cartilage in a goat model-A preliminary study. J. Bone Jt. Surg. - Ser. A, 2001, 83(1), 53-64.
Kock, L.; Van Donkelaar, C.C.; Ito, K. Tissue engineering of functional articular cartilage: the current status. Cell Tissue Res., 2012, 347, 613-627.
Pittenger, M.F.; Mackay, A.M.; Beck, S.C.; Jaiswal, R.K.; Douglas, R.; Mosca, J.D.; Moorman, M.A.; Simonetti, D.W.; Craig, S.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411), 143-147.
Savkovic, V.; Li, H.; Seon, J.K.; Hacker, M.; Franz, S.S.J. Mesenchymal stem cells in cartilage regeneration. Curr. Stem Cell Res. Ther., 2014, 9(6), 469-488.
Friedenstein, A.J.; Piatetzky-Shapiro, I.I.; Petrakova, K.V. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol., 1966, 16, 381-390.
Crisan, M.; Yap, S.; Casteilla, L.; Chen, C.W.; Corselli, M.; Park, T.S.; Andriolo, G.; Sun, B.; Zheng, B.; Zhang, L.; Norotte, C.; Teng, P.N.; Traas, J.; Schugar, R.; Deasy, B.M.; Badylak, S.; Buhring, H.J.; Giacobino, J.P.; Lazzari, L.; Huard, J.; Péault, B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 2008, 3(3), 301-313.
Kristjansson, B.; Limthongkul, W.; Yingsakmongkol, W.; Thantiworasit, P.; Jirathanathornnukul, N.; Honsawek, S. Isolation and characterization of human mesenchymal stem cells from facet joints and interspinous ligaments. Spine (Phila. Pa. 1976), 2016, 41(1), E1-E7.
Chen, Y.T.; Wei, J.D.; Wang, J.P.; Lee, H.H.; Chiang, E.R.; Lai, H.C.; Chen, L.L.; Lee, Y.T.; Tsai, C.C.; Liu, C.L.; Hung, S.C. Isolation of mesenchymal stem cells from human ligamentum flavum: implicating etiology of ligamentum flavum hypertrophy. Spine (Phila. Pa. 1976), 2011, 36(18), E1193-E1200.
Calabrese, G.; Giuffrida, R.; Forte, S.; Fabbi, C.; Figallo, E.; Salvatorelli, L.; Memeo, L.; Parenti, R.; Gulisano, M.; Gulino, R. Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse. Sci. Rep., 2017, 7(1), 7110.
Szychlinska, M.A.; Castrogiovanni, P.; Nsir, H.; Di Rosa, M.; Guglielmino, C.; Parenti, R.; Calabrese, G.; Pricoco, E.; Salvatorelli, L.; Magro, G.; Imbesi, R.; Mobasheri, A.; Musumeci, G. Engineered cartilage regeneration from adipose tissue derived-mesenchymal stem cells: A morphomolecular study on osteoblast, chondrocyte and apoptosis evaluation. Exp. Cell Res., 2017, 357(2), 222-235.
Abumaree, M.; Al Jumah, M.; Pace, R.A.; Kalionis, B. Immunosuppressive properties of mesenchymal stem cells. Stem Cell Rev., 2012, 8, 375-392.
Mahmoudifar, N.; Doran, P.M. Chondrogenesis and cartilage tissue engineering: The longer road to technology development. Trends Biotechnol., 2012, 30, 166-176.
Grassel, S. Influence of cellular microenvironment and paracrine signals on chondrogenic differentiation. Front. Biosci., 2007, 12(12), 4946.
Bonyadi Rad, E.; Musumeci, G.; Pichler, K.; Heidary, M.; Szychlinska, M.A.; Castrogiovanni, P.; Marth, E.; Böhm, C.; Srinivasaiah, S.; Krönke, G.; Weinberg, A.; Schäfer, U. Runx2 mediated Induction of novel targets ST2 and Runx3 leads to cooperative regulation of hypertrophic differentiation in ATDC5 chondrocytes. Sci. Rep., 2017, 7(1), 17947.
Jiang, X.; Huang, X.; Jiang, T.; Zheng, L.; Zhao, J.; Zhang, X. The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs). Biomater. Sci., 2018, 6(6), 1556-1568.
Almalki, S.G.; Agrawal, D.K. Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation, 2016, 92(1-2), 41-51.
López-Ruiz, E.; Jiménez, G.; Kwiatkowski, W.; Montañez, E.; Arrebola, F.; Carrillo, E.; Choe, S.; Marchal, J.A.; Perán, M. Impact of TGF-β family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients. Eur. Cell. Mater., 2018, 35, 209-224.
Lu, Y.T.; Wei, L.S.; Wang, Z.Y.; Li, W.; Duan, Y.W.; Gao, M.; Liu, J.; Zhao, Y.H.; Li, S.L. TGF-β3 improves bone mesenchymal stem cells toward chondrogenic differentiation under hypoxia environment. Zhonghua Yi Xue Za Zhi, 2018, 98(27), 2198-2202.
Sekiya, I.; Larson, B.L.; Vuoristo, J.T.; Reger, R.L.; Prockop, D.J. Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma. Cell Tissue Res., 2005, 320(2), 269-276.
Vater, C.; Kasten, P.; Stiehler, M. Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater., 2011, 7(2), 463-477.
Schmidt, M.B.; Chen, E.H.; Lynch, S.E. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis cartilage. Osteoarthritis Cartilage, 2006, 14(5), 403-412.
Gugjoo, M.B. Amarpal; Abdelbaset-Ismail, A.; Aithal, H.P.; Kinjavdekar, P.; Pawde, A.M.; Kumar, G.S.; Sharma, G.T. Mesenchymal stem cells with IGF-1 and TGF- β1 in laminin gel for osteochondral defects in rabbits. Biomed. Pharmacother., 2017, 93, 1165-1174.
Ellman, M.B.; An, H.S.; Muddasani, P.; Im, H.J. Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene, 2008, 420(1), 82-89.
Bae, H.C.; Park, H.J.; Wang, S.Y.; Yang, H.R.; Lee, M.C.; Han, H.S. Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem cells. Biomater. Res., 2018, 26, 22-28.
Jeng, L.; Olsen, B.R.; Spector, M. Engineering endostatin-producing cartilaginous constructs for cartilage repair using nonviral transfection of chondrocyte-seeded and mesenchymal-stem-cell-seeded collagen scaffolds. Tissue Eng. Part A, 2010, 16(10), 3011-3021.
Emans, P.J.; van Rhijn, L.W.; Welting, T.J.M.; Cremers, A.; Wijnands, N.; Spaapen, F.; Voncken, J.W.; Shastri, V.P. Autologous engineering of cartilage. Proc. Natl. Acad. Sci., 2010, 107(8), 3418-3423.
Matsumoto, T.; Cooper, G.M.; Gharaibeh, B.; Meszaros, L.B.; Li, G.; Usas, A.; Fu, F.H.; Huard, J. Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum., 2009, 60(5), 1390-1405.
Nagai, T.; Sato, M.; Kutsuna, T.; Kokubo, M.; Ebihara, G.; Ohta, N.; Mochida, J. Intravenous administration of anti-vascular endothelial growth factor humanized monoclonal antibody bevacizumab improves articular cartilage repair. Arthritis Res. Ther., 2010, 12(5), R178.
Zhang, F.; Leong, W.; Su, K.; Fang, Y.; Wang, D-A. A transduced living hyaline cartilage graft releasing transgenic stromal cell-derived factor-1 inducing endogenous stem cell homing in vivo. In Vivo. Tissue Eng. Part A, 2013, 19(9-10), 1091-1099.
Chen, P.; Tao, J.; Zhu, S.; Cai, Y.; Mao, Q.; Yu, D.; Dai, J.; Ouyang, H.W. Radially oriented collagen scaffold with SDF-1 promotes osteochondral repair by facilitating cell homing. Biomaterials, 2015, 39, 114-123.
Orth, P.; Cucchiarini, M.; Zurakowski, D.; Menger, M.D.; Kohn, D.M.; Madry, H. Parathyroid hormone improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo. Osteoarthritis Cartilage, 2013, 21(4), 614-624.
Zhang, W.; Chen, J.; Tao, J.; Hu, C.; Chen, L.; Zhao, H.; Xu, G.; Heng, B.C.; Ouyang, H.W. The promotion of osteochondral repair by combined intra-articular injection of parathyroid hormone-related protein and implantation of a bi-layer collagen-silk scaffold. Scaffold Biomat., 2013, 34(25), 6046-6057.
Dang, A.C.; Warren, A.P.; Kim, H.T. Beneficial effects of intra-articular caspase inhibition therapy following osteochondral injury. Osteoarthritis Cartilage, 2006, 14(6), 526-532.
Gilbert, S.J.; Singhrao, S.K.; Khan, I.M.; Gonzalez, L.G.; Thomson, B.M.; Burdon, D.; Duance, V.C.; Archer, C.W. Enhanced tissue integration during cartilage repair in vitro can be achieved by inhibiting chondrocyte death at the wound edge. Tissue Eng. Part A, 2009, 15(7), 1739-1749.
Yamamoto, A.; Warren, A.P.; Kim, H.T. Minocycline reduces articular cartilage damage following osteochondral injury. Knee, 2012, 19(5), 680-683.
Chen, P.; Zhu, S.; Wang, Y.; Mu, Q.; Wu, Y.; Xia, Q.; Zhang, X.; Sun, H.; Tao, J.; Hu, H.; Lu, P.; Ouyang, H. The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel. Biomaterials, 2014, 35(9), 2827-2836.
Lenas, P.; Luyten, F.P.; Doblare, M.; Nicodemou-Lena, E.; Lanzara, A.E. Modularity in developmental biology and artificial organs: a missing concept in tissue engineering. Artif. Organs, 2011, 35(6), 656-662.
Schon, B.S.; Hooper, G.J.; Woodfield, T.B.F. Modular tissue assembly strategies for biofabrication of engineered cartilage. Ann. Biomed. Eng., 2017, 45(1), 100-114.
Welter, J.F.; Solchaga, L.A.; Penick, K.J. Simplification of aggregate culture of human mesenchymal stem cells as a chondrogenic screening assay. Biotechniques, 2007, 42(6), 732-737.
Im, G-I.; Jung, N-H.; Tae, S-K. Chondrogenic differentiation of mesenchymal stem cells isolated from patients in late adulthood: The optimal conditions of growth factors. Tissue Eng., 2006, 12(3), 527-536.
Kafienah, W.; Mistry, S.; Dickinson, S.C.; Sims, T.J.; Learmonth, I.; Hollander, A.P. Three-dimensional cartilage tissue engineering using adult stem cells from osteoarthritis patients. Arthritis Rheum., 2007, 56(1), 177-187.
Musumeci, G.; Mobasheri, A.; Trovato, F.M.; Szychlinska, M.A.; Graziano, A.C.E.; Lo Furno, D.; Avola, R.; Mangano, S.; Giuffrida, R.; Cardile, V. Biosynthesis of collagen I, II, RUNX2 and lubricin at different time points of chondrogenic differentiation in a 3D in vitro model of human mesenchymal stem cells derived from adipose tissue. Acta Histochem., 2014, 116(8), 1407-1417.
Steinert, A.F.; Ghivizzani, S.C.; Rethwilm, A.; Tuan, R.S.; Evans, C.H.; Nöth, U. Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res. Ther., 2007, 9, 213.
Weiss, S.; Hennig, T.; Bock, R.; Steck, E.; Richter, W. Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J. Cell. Physiol., 2010, 223(1), 84-93.
Endo, K.; Fujita, N.; Nakagawa, T.; Nishimura, R. Effect of fibroblast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis. Tissue Eng. Part A, 2018.
Fan, Y.; Jianying, F.; Chenyan, L.; Pan, W.; Zhe, S.; Changjing, S. Influence on Indian hedgehog-parathyroid hormone-like related protein pathway induced by altered masticatory loading in the condylar cartilage of growing rabbits. Hua Xi Kou Qiang Yi Xue Za Zhi, 2017, 35(2), 127-132.
Schlegel, W.; Raimann, A.; Halbauer, D.; Scharmer, D.; Sagmeister, S.; Wessner, B.; Helmreich, M.; Haeusler, G.; Egerbacher, M. Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate. PLoS One, 2013, 8(10)
Luo, Z.; Jiang, L.; Xu, Y.; Li, H.; Xu, W.; Wu, S.; Wang, Y.; Tang, Z.; Lv, Y.; Yang, L. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model. Biomaterials, 2015, 52(1), 463-475.
Bouffi, C.; Thomas, O.; Bony, C.; Giteau, A.; Venier-Julienne, M.C.; Jorgensen, C.; Montero-Menei, C.; Noël, D. The role of pharmacologically active microcarriers releasing TGF-beta3 in cartilage formation in vivo by mesenchymal stem cells. Biomaterials, 2010, 31(25), 6485-6493.
Kim, D.K. In Kim, J.; Sim, B.R.; Khang, G. Bioengineered porous composite curcumin/silk scaffolds for cartilage regeneration. Mater. Sci. Eng. C, 2017, 78, 571-578.
Focaroli, S.; Teti, G.; Salvatore, V.; Orienti, I.; Falconi, M. Calcium/ Cobalt alginate beads as functional scaffolds for cartilage tissue engineering. Stem Cells Int, 2016, 2016
Zhu, W.; Castro, N.J.; Cheng, X.; Keidar, M.; Zhang, L.G. Cold atmospheric plasma modified electrospun scaffolds with embedded microspheres for improved cartilage regeneration. PLoS One, 2015, 10(7)
Kim, C.; Jeon, O.H.; Kim, D.H.; Chae, J.J.; Shores, L.; Bernstein, N.; Bhattacharya, R.; Coburn, J.M.; Yarema, K.J.; Elisseeff, J.H. Local delivery of a carbohydrate analog for reducing arthritic inflammation and rebuilding cartilage. Biomaterials, 2016, 83, 93-101.
Zhou, F.; Zhang, X.; Cai, D.; Li, J.; Mu, Q.; Zhang, W.; Zhu, S.; Jiang, Y.; Shen, W.; Zhang, S.; Ouyang, H.W. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair. Acta Biomater., 2017, 63, 64-75.
Wang, W.; Sun, L.; Zhang, P.; Song, J.; Liu, W. An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits. Acta Biomater., 2014, 10(12), 4983-4995.
Bedouet, L.; Moine, L.; Pascale, F.; Nguyen, V.N.; Labarre, D.; Laurent, A. Synthesis of hydrophilic intra-articular microspheres conjugated to ibuprofen and evaluation of anti-inflammatory activity on articular explants. Int. J. Pharm., 2014, 459, 51-61.
Ko, J.Y.; Choi, Y.J.; Jeong, G.J.; Im, G.I. Sulforaphane-PLGA microspheres for the intra-articular treatment of osteoarthritis. Biomaterials, 2013, 34, 5359-5368.
Whitmire, R.E.; Wilson, D.S.; Singh, A.; Levenston, M.E.; Murthy, N.; Garcia, A.J. Self-assembling nanoparticles for intra-articular delivery of anti-inflammatory proteins. Biomaterials, 2012, 33, 7665-7675.
Sundman, E.A.; Cole, B.J.; Karas, V.; Della Valle, C.; Tetreault, M.W.; Mohammed, H.O.; Fortier, L.A. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am. J. Sports Med., 2014, 42, 35-41.
Smyth, N.A.; Haleem, A.M.; Murawski, C.D.; Do, H.T.; Deland, J.T.; Kennedy, J.G. The effect of platelet-rich plasma on autologous osteochondral transplantation: An in vivo rabbit model. J. Bone Joint Surg. Am., 2013, 95, 2185-2193.
Moutos, F.T.; Freed, L.E.; Guilak, F. A biomimetic threedimensional woven composite scaffold for functional tissue engineering of cartilage. Nat. Mater., 2007, 6(2), 162-167.
Zhao, H.; Ma, L.; Gong, Y.; Gao, C.; Shen, J. A pol\lactLde/fibrLn gel composite scaffold for cartilage tissue engineering: Fabrication and an in vitro evaluation. J. Mater. Sci. Mater. Med., 2009, 20, 135-143.
Tanaka, Y.; Yamaoka, H.; Nishizawa, S.; Nagata, S.; Ogasawara, T.; Asawa, Y.; Fujihara, Y.; Takato, T.; Hoshi, K. The optimization of porous polymeric scaffolds for chondrocyte/ atelocollagen based tissue-engineered cartilage. Biomaterials, 2010, 31(16), 4506-4516.
Uematsu, K.; Hattori, K.; Ishimoto, Y.; Yamauchi, J.; Habata, T.; Takakura, Y.; Ohgushi, H.; Fukuchi, T.; Sato, M. Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lacticglycolic acid (PLGA) scaffold. Biomaterials, 2005, 26(20), 4273-4279.
Park, G.E.; Pattison, M.A.; Park, K.; Webster, T.J. Accelerated chondrocyte functions on NaOH-treated PLGA scaffolds. Biomaterials, 2005, 26(16), 3075-3082.
Fan, H.; Hu, Y.; Zhang, C.; Li, X.; Lv, R.; Qin, L.; Zhu, R. Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials, 2006, 27(26), 4573-4580.
Park, K.; Cho, K.J.; Kim, J.J.; Kim, I.H.; Han, D.K. Functional PLGA scaffolds for chondrogenesis of bone-marrow-derived mesenchymal stem cells. Macromol. Biosci., 2009, 9, 221-229.
Chiari, C.; Koller, U.; Dorotka, R.; Eder, C.; Plasenzotti, R.; Lang, S.; Ambrosio, L.; Tognana, E.; Kon, E.; Salter, D.; Nehrer, S. A tissue engineering approach to meniscus regeneration in a sheep model. Osteoarthritis Cartilage, 2006, 14(10), 1056-1065.
Morille, M.; Toupet, K.; Montero-Menei, C.N.; Jorgensen, C. Noël, PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis. Biomaterials, 2016, 88, 60-69.
Thiem, A.; Bagheri, M.; Große-Siestrup, C.; Zehbe, R. Gelatin-poly(lactic-co-glycolic acid) scaffolds with oriented pore channel architecture - From in vitro to in vivo testing. Mater. Sci. Eng. C, 2016, 62, 585-595.
Siclari, A.; Mascaro, G.; Gentili, C.; Cancedda, R.; Boux, E. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clin. Orthop. Relat. Res., 2012, 470(3), 910-919.
Siclari, A.; Mascaro, G.; Kaps, C.; Boux, E. A 5-year follow-up after cartilage repair in the knee using a platelet-rich plasma-immersed polymer-based implant. Open Orthop. J., 2014, 8, 346-354.
Siclari, A.; Mascaro, G.; Gentili, C.; Kaps, C.; Cancedda, R.; Boux, E. Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant. Knee Surg. Sports Traumatol. Arthrosc., 2014, 22(6), 1225-1234.
Enea, D.; Cecconi, S.; Calcagno, S.; Busilacchi, A.; Manzotti, S.; Kaps, C.; Gigante, A. Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate. Knee, 2013, 20(6), 562-569.
DeLee, J.; Drez, D.; Miller, M.D. Delee & Drez’s Orthopaedic Sports Medicine Principles and Practice, 3rd ed; Saunders/Elsevier: Philadelphia, PA, USA, 2010.
Elisseeff, J.; Anseth, K.; Sims, D.; McIntosh, W.; Randolph, M.; Langer, R. Transdermal photopolymerization for minimally invasive implantation. Proc. Natl. Acad. Sci., 1999, 96(6), 3104-3107.
Hwang, N.S.; Varghese, S.; Li, H.; Elisseeff, J. Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels. Cell Tissue Res., 2011, 344, 499-509.
Nguyen, L.H.; Kudva, A.K.; Saxena, N.S.; Roy, K. 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(29), 6946-6952.
Zhu, J. Bioactive modification of poly(ethyleneglycol) hydrogels for tissue engineering. Biomaterials, 2010, 31, 4639-4656.
Musumeci, G.; Carnazza, M.L.; Loreto, C.; Leonardi, R.; Loreto, C. β-defensin-4 (HBD-4) is expressed in chondrocytes derived from normal and osteoarthritic cartilage encapsulated in PEGDA scaffold. Acta Histochem., 2012, 114(8), 805-812.
Musumeci, G.; Loreto, C.; Carnazza, M.L.; Coppolino, F.; Cardile, V.; Leonardi, R. Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly(ethylene glycol) diacrylate (PEGDA) scaffold. Eur. J. Histochem., 2011, 55(3), 31.
Musumeci, G.; Loreto, C.; Carnazza, M.L.; Strehin, I.; Elisseeff, J. OA cartilage derived chondrocytes encapsulated in poly(ethylene glycol) diacrylate (PEGDA) for the evaluation of cartilage restoration and apoptosis in an in vitro model. Histol. Histopathol., 2011, 26(10), 1265-1278.
Chen, Z.; Zhao, M.; Liu, K.; Wan, Y.; Li, X.; Feng, G. Novel chitosan hydrogel formed by ethylene glycol chitosan, 1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold: In vitro and in vivo evaluation. J. Mater. Sci. Mater. Med., 2014, 25(8), 1903-1913.
Scholz, B.; Kinzelmann, C.; Benz, K.; Mollenhauer, J.; Wurst, H.; Schlosshauer, B. Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration. Eur. Cell. Mater., 2010, 20, 24-37.
Neumann, A.J.; Quinn, T.; Bryant, S.J. Nondestructive evaluation of a new hydrolytically degradable and photo-clickable PEG hydrogel for cartilage tissue engineering. Acta Biomater., 2016, 39, 1-11.
Wang, J.; Zhang, F.; Tsang, W.P.; Wan, C.; Wu, C. Fabrication of injectable high strength hydrogel based on 4-arm star PEG for cartilage tissue engineering. Biomaterials, 2017, 120, 11-21.
Kon, E.; Chiari, C.; Marcacci, M.; Delcogliano, M.; Salter, D.M.; Martin, I.; Ambrosio, L.; Fini, M.; Tschon, M.; Tognana, E.; Plasenzotti, R.; Nehrer, S. Tissue engineering for total meniscal substitution: Animal study in sheep model. Tissue Eng. Part A, 2008, 14, 1067-1080.
Sung, M.L.; Sung, H.J.; Se, H.O.; Soon, H.Y.; Gun, I.I.; Jin, H.L. Dual-growth-factor-releasing PCL scaffolds for chondrogenesis of adipose-tissue-derived mesenchymal stem cells. Adv. Eng. Mater., 2010, 12, 1-2.
Jeong, C.G.; Zhang, H.; Hollister, S.J. Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification. J. Biomed. Mater. Res. - Part A, 2012, 100, A(8), 2088-2096.
Esposito, A.R.; Moda, M.; Cattani, S.M. de M.; de Santana, G.M.; Barbieri, J.A.; Munhoz, M.M.; Cardoso, T.P.; Barbo, M.L.P.; Russo, T.; D’Amora, U.; Gloria, A.; Ambrosio, L.; Duek, E.A. PLDLA/PCL-T Scaffold for meniscus tissue engineering. Biores. Open Access, 2013, 2(2), 138-147.
Russo, L.; Russo, T.; Battocchio, C.; Taraballi, F.; Gloria, A.; D’Amora, U.; De Santis, R.; Polzonetti, G.; Nicotra, F.; Ambrosio, L.; Cipolla, L. Galactose grafting on poly (ε-caprolactone) substrates for tissue engineering: a preliminary study. Carbohydr. Res., 2015, 405, 39-46.
Russo, L.; Gloria, A.; Russo, T.; D’Amora, U.; Taraballi, F.; De Santis, R.; Ambrosio, L.; Nicotra, F.; Cipolla, L. Glucosamine grafting on poly (ε-caprolactone): A novel glycated polyester as a substrate for tissue engineering. RSC Advances, 2013, 3(18), 6286-6289.
D’Amora, U.; D’Este, M.; Eglin, D.; Safari, F.; Sprecher, C.M.; Gloria, A.; De Santis, R.; Alini, M.; Ambrosio, L. Collagen density gradient on three-dimensional printed poly(ε-caprolactone) scaffolds for interface tissue engineering. J. Tissue Eng. Regen. Med., 2018, 12(2), 321-329.
Tuli, R.; Li, W.J.; Tuan, R.S. Current state of cartilage tissue engineering. Arthritis Res. Ther., 2003, 5(5), 235-238.
Wang, C.C.; Yang, K.C.; Lin, K.H.; Liu, Y.L.; Liu, H.C.; Lin, F.H. Cartilage regeneration in scid mice using a highly organized three-dimensional alginate scaffold. Biomaterials, 2012, 33(1), 120-127.
Hao, T.; Wen, N.; Cao, J.K.; Wang, H.B.; Lu, S.H.; Liu, T.; Lin, Q.X.; Duan, C.M.; Wang, C.Y. The support of matrix accumulation and the promotion of sheep articular cartilage defects repair in vivo by chitosan hydrogels. Osteoarthritis Cartilage, 2010, 18, 257-265.
Filová, E.; Jakubcová, B.; Danilová, I.; Kuželová Košťáková, E.; Jarošíková, T.; Chernyavskiy, O.; Hejda, J.; Handl, M.; Beznoska, J.; Nečas, A.; Rosina, J.; Amler, E. Polycaprolactone foam functionalized with chitosan microparticles - a suitable scaffold for cartilage regeneration. Physiol. Res., 2016, 65(1), 121-131.
Park, K.M.; Lee, S.Y.; Joung, Y.K.; Na, J.S.; Lee, M.C.; Park, K.D. Thermosensitive chitosan-pluronic hydrogel as an injectable cell delivery carrier for cartilage regeneration. Acta Biomater., 2009, 5(6), 1956-1965.
Chenite, A.; Chaput, C.; Wang, D.; Combes, C.; Buschmann, M.D.; Hoemann, C.D.; Leroux, J.C.; Atkinson, B.L.; Binette, F.; Selmani, A. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials, 2000, 21(21), 2155-2161.
Dumitriu, S.; Popa, V.I. Polymeric biomaterials; CRC Press: Boca Raton, FL, USA, 2013, pp. 318-324.
Gohil, S.V. 7-Chitosan-Based Scaffolds For Growth Factor Delivery. In: Chitosan Based Biomaterials; Bumgardner, J.D., Ed.; Woodhead Publishing, 2016; Vol. 2, pp. 175-207.
Nettles, D.L.; Vail, T.P.; Morgan, M.T.; Grinstaff, M.W.; Setton, L.A. Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair. Ann. Biomed. Eng., 2004, 32(3), 391-397.
Liao, E.; Yaszemski, M.; Krebsbach, P.; Hollister, S. Tissue-engineered cartilage constructs using composite hyaluronic acid/collagen i hydrogels and designed poly(propylene fumarate) scaffolds. Tissue Eng., 2007, 13(3), 537-550.
Rampichová, M.; Filová, E.; Varga, F.; Lytvynets, A.; Prosecká, E.; Koláčná, L.; Motlík, J.; Nečas, A.; Vajner, L.; Uhlík, J.; Amler, E. Fibrin/hyaluronic acid composite hydrogels as appropriate scaffolds for in vivo artificial cartilage implantation. ASAIO J., 2010, 56(6), 563-568.
Johnstone, B.; Alini, M.; Cucchiarini, M.; Dodge, G.R.; Eglin, D.; Guilak, F.; Madry, H.; Mata, A.; Mauck, R.L.; Semino, C.E.; Stoddart, M.J. Tissue engineering for articular cartilage repair - the state of the art. Eur. Cell. Mater., 2012, 25, 248-267.
Mortisen, D.; Peroglio, M.; Alini, M.; Eglin, D. Tailoring thermoreversible hyaluronan hydrogels by “click” chemistry and raft polymerization for cell and drug therapy. Biomacromolecules, 2010, 11(5), 1261-1272.
D’Amora, U.; Ronca, A.; Raucci, M.G.; Lin, H.; Soriente, A.; Fan, Y.; Zhang, X.; Ambrosio, L. Bioactive composites based on double network approach with tailored mechanical, physico-chemical, and biological features. J. Biomed. Mat. Res. - Part A, 2018, 106, 3079-3089.
Ronca, A.; D’Amora, U.; Raucci, M.G.; Lin, H.; Fan, Y.; Zhang, X.; Ambrosio, L. A combined approach of double network hydrogel and nanocomposites based on hyaluronic acid and poly(ethylene glycol) diacrylate blend. Materials, 2018, 11(12), 2454.
Pascual-Garrido, C.; Rodeo, S.A. Biology of Cartilage regeneration, in hip joint restoration; Springer, 2017, pp. 657-663.
Yuan, T.; Li, K.; Guo, L.; Fan, H.; Zhang, X. Modulation of immunological properties of allogeneic mesenchymal stem cells by collagen scaffolds in cartilage tissue engineering. J. Biomed. Mat. Res. - Part A, 2011, 98A(3), 332-341.
Stoddart, M.J.; Grad, S.; Eglin, D.; Alini, M. Cells and biomaterials in cartilage tissue engineering. Regen. Med., 2009, 4, 81-98.
Chen, W.C.; Yao, C.L.; Wei, Y.H.; Chu, I.M. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology, 2011, 63(1), 13-23.
Almeida, H.V.; Eswaramoorthy, R.; Cunniffe, G.M.; Buckley, C.T.; O’Brien, F.J.; Kelly, D.J. Fibrin hydrogels functionalized with cartilage extracellular matrix and incorporating freshly isolated stromal cells as an injectable for cartilage regeneration. Acta Biomater., 2016, 36, 55-62.
Jeuken, R.; Roth, A.; Peters, R.; van Donkelaar, C.C.; Thies, J.C.; van Rhijn, L.W.; Emans, P.J. Polymers in cartilage defect repair of the knee: Current status and future prospects. Polymers, 2016, 8(6), 219.
Campoccia, D.; Doherty, P.; Radice, M.; Brun, P.; Abatangelo, G.; Williams, D.F. Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials, 1998, 19, 2101-2127.
Barbucci, R.; Magnani, A.; Rappuoli, R.; Lamponi, S.; Consumi, M. Immobilisation of sulphated hyaluronan for improved biocompatibility. J. Inorg. Biochem., 2000, 79(1-4), 119-125.
Filardo, G.; Kon, E.; Di Martino, A.; Iacono, F.; Marcacci, M. Arthroscopic second-generation autologous chondrocyte implantation: A prospective 7-year follow-up study. Am. J. Sports Med., 2011, 39(10), 2153-2160.
Kon, E.; Gobbi, A.; Filardo, G.; Delcogliano, M.; Zaffagnini, S.; Marcacci, M. Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: prospective nonrandomized study at 5 years. Am. J. Sports Med., 2009, 37(1), 33-41.
Mironov, V.; Trusk, T.; Kasyanov, V.; Little, S.; Swaja, R.; Markwald, R. Biofabrication: A 21st century manufacturing paradigm. Biofabrication, 2009, 1(2)
Wallace, G.; Cornock, R.; O’Connel, C.; Beirne, S.; Gilbert, F.; Dodds, S.; Bjorklund, M. 3D Bioprinting: Printing Parts for Bodies; ARC Centre of Excellence for Electromaterials Science, 2014.
Jung, J.W.; Kang, H.W.; Kang, T.Y.; Park, J.H.; Park, J.; Cho, D.W. Projection image-generation algorithm for fabrication of a complex structure using projection-based microstereolithography. Int. J. Precis. Eng. Manuf., 2012, 13(3), 445-449.
Lee, J.W.; Kang, K.S.; Lee, S.H.; Kim, J.Y.; Lee, B.K.; Cho, D.W. Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)/diethyl fumarate photopolymer 3d scaffold incorporating bmp-2 loaded PLGA microspheres. Biomaterials, 2011, 32(3), 744-752.
Chung, J.H.Y.; Naficy, S.; Yue, Z.; Kapsa, R.; Quigley, A.; Moulton, S.E.; Wallace, G.G. Bio-ink properties and printability for extrusion printing living cells. Biomater. Sci., 2013, 1(7), 763-773.
Nakamura, M.; Kobayashi, A.; Takagi, F.; Watanabe, A.; Hiruma, Y.; Ohuchi, K.; Iwasaki, Y.; Horie, M.; Morita, I.; Takatani, S. Biocompatible inkjet printing technique for designed seeding of individual living cells. Tissue Eng., 2005, 11(11-12), 1658-1666.
Ferris, C.J.; Gilmore, K.G.; Wallace, G.G.; Panhuis, M. Biofabrication: An overview of the approaches used for printing of living cells. Appl. Microbiol. Biotechnol., 2013, 97(10), 4243s-4258s.
Simpson, R.L.; Wiria, F.E.; Amis, A.A.; Chua, C.K.; Leong, K.F.; Hansen, U.N.; Chandrasekaran, M.; Lee, M.W. Development of a 95/5 poly(l-lactide-co-glycolide)/hydroxylapatite and β-tricalcium phosphate scaffold as bone replacement material via selective laser sintering. J. Biomed. Mat. Res. - Part A Appl. Biomater., 2008, 84(1), 17-25.
Iulian, A.; Dan, L.; Camelia, T.; Claudia, M.; Sebastian, G. Synthetic materials for osteochondral tissue engineering. Adv. Exp. Med. Biol., 2018, (1058), 31-52.
Tibbits, S. 4D Printing: Multi-material shape change. Archit. Des., 2014, 84(1), 116-121.
Kundu, J.; Shim, J.H.; Jang, J.; Kim, S.W.; Cho, D.W. An additive manufacturing-based pcl-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering. J. Tissue Eng. Regen. Med., 2015, 9(11), 1286-1297.
Xao, T.; Binder, K.W.; Albanna, M.Z.; Dice, D.; Zhao, W.; Yoo, J.J.; Atala, A. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication, 2013, 5(1)
Cui, X.; Breitenkamp, K.; Finn, M.G.; Lotz, M.; D’Lima, D.D. Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng. Part A, 2012, 18(11-12), 1304-1312.
Levato, R.; Visser, J.; Planell, J.A.; Engel, E.; Malda, J.; Mateos-Timoneda, M.A. Biofabrication of tissue constructs by 3d bioprinting of cell-laden microcarriers. Biofabrication, 2014, 6(3)
Hung, K.C.; Tseng, C.S.; Dai, L.G.; Hsu, S. Hui water-based polyurethane 3d printed scaffolds with controlled release function for customized cartilage tissue engineering. Biomaterials, 2016, 83, 156-168.
Kesti, M.; Müller, M.; Becher, J.; Schnabelrauch, M.; D’Este, M.; Eglin, D.; Zenobi-Wong, M. A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation. Acta Biomater., 2015, 11(1), 162-172.
Oliveira, I.; Vieira, S.; Oliveira, J.M.; Reis, R.L. Nanoparticles-based systems for osteochondral tissue engineering. Adv. Exp. Med. Biol., 2018, (1059), 209-217.
Mukherjee, B. Editorial (Thematic Issue: “Nanosize Drug Delivery System”). Curr. Pharm. Biotechnol., 2014, 14(15), 1221-1221.
Vasita, R.; Katti, D.S. Nanofibers and their applications in tissue engineering. Int. J. Nanomedicine, 2006, 1(1), 15-30.
D’Antimo, C.; Biggi, F.; Borean, A.; Di Fabio, S.; Pirola, I. Combining a novel leucocyte-platelet-concentrated membrane and an injectable collagen scaffold in a single-step amic procedure to treat chondral lesions of the knee: A preliminary retrospective study. Eur. J. Orthop. Surg. Traumatol., 2017, 27(5), 673-681.
Da Silva Meirelles, L.; Fontes, A.M.; Covas, D.T.; Caplan, A.I. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev., 2009, 20, 419-427.
Murphy, M.B.; Moncivais, K.; Caplan, A.I. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Experiment. Mol. Med, 2013, 45, 54.
Lee, M.J.; Kim, J.; Kim, M.Y.; Bae, Y.S.; Ryu, S.H.; Lee, T.G.; Kim, J.H. Proteomic analysis of tumor necrosis factor-α-induced secretome of human adipose tissue-derived mesenchymal stem cells. J. Proteome Res., 2010, 9(4), 1754-1762.
Von Bahr, L.; Batsis, I.; Moll, G.; Hägg, M.; Szakos, A.; Sundberg, B.; Uzunel, M.; Ringden, O.; Le Blanc, K. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells, 2012, 30(7), 1575-1578.
Gnecchi, M.; Zhang, Z.; Ni, A.; Dzau, V.J. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res., 2008, 1416, 123-146.
Kordelas, L.; Rebmann, V.; Ludwig, A-K.; Radtke, S.; Ruesing, J.; Doeppner, T.R.; Epple, M.; Horn, P.A.; Beelen, D.W.; Giebel, B. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia, 2014, 28, 970-973.
Lai, R.C.; Arslan, F.; Lee, M.M.; Sze, N.S.K.; Choo, A.; Chen, T.S.; Salto-Tellez, M.; Timmers, L.; Lee, C.N.; El Oakley, R.M.; Pasterkamp, G.; de Kleijn, D.P.; Lim, S.K. Exosome secreted by msc reduces myocardial ischemia/reperfusion injury. Stem Cell Res., 2010, 4(3), 214-222.
Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; Xu, W. HucMSc-Exosome mediated-wnt4 signaling is required for cutaneous wound healing. Stem Cells, 2015, 33(7), 2158-2168.
Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9, 654-659.
Hood, J.L.; San Roman, S.; Wickline, S.A. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res., 2011, 71(11), 3792-3801.
Altevogt, P.; Bretz, N.P.; Ridinger, J.; Utikal, J.; Umansky, V. Novel insights into exosome-induced, tumor-associated inflammation and immunomodulation. Semin. Cancer Biol., 2014, 28, 51-57.
Robbins, P.D.; Morelli, A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol., 2014, 14, 195-208.
Vonk, L.A.; van Dooremalen, S.F.J.; Liv, N.; Klumperman, J.; Coffer, P.J.; Saris, D.B.F.; Lorenowicz, M.J. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics, 2018, 8(4), 906-920.
Zhang, S.; Chu, W.C.; Lai, R.C.; Lim, S.K.; Hui, J.H.P.; Toh, W.S. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage, 2016, 24(12), 2135-2140.
Toh, W.S.; Lai, R.C.; Hui, J.H.P.; Lim, S.K. MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Semin. Cell Dev. Biol., 2017, 67, 56-64.
Malda, J.; Boere, J.; Van De Lest, C.H.A.; Van Weeren, P.R.; Wauben, M.H.M. Extracellular vesicles - new tool for joint repair and regeneration. Nat. Rev. Rheumatol., 2016, 12(4), 243-249.
Liu, X.; Yang, Y.; Li, Y.; Niu, X.; Zhao, B.; Wang, Y.; Bao, C.; Xie, Z.; Lin, Q.; Zhu, L. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale, 2017, 9(13), 4430-4438.
Gardner, O.F.W.; Musumeci, G.; Neumann, A.J.; Eglin, D.; Archer, C.W.; Alini, M.; Stoddart, M.J. Asymmetrical seeding of mscs into fibrin-poly(ester-urethane) scaffolds and its effect on mechanically induced chondrogenesis. J. Tissue Eng. Regen. Med., 2017, 11(10), 2912-2921.
Li, Z.; Yao, S.J.; Alini, M.; Stoddart, M. Chondrogenesis of human bone marrow mesenchymal stem cells is modulated by frequency and amplitude of dynamic compression and shear stress. Eur. Cell. Mater., 2009, 18(Suppl. 1), 51.
Musumeci, G. The effect of mechanical loading on articular cartilage. J. Funct. Morphol. Kinesiol., 2016, 1, 154-161.
Musumeci, G.; Castrogiovanni, P.; Trovato, F.M.; Imbesi, R.; Giunta, S.; Szychlinska, M.A.; Loreto, C.; Castorina, S.; Mobasheri, A. Physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression. Scand. J. Med. Sci. Sports, 2015, 25(2), e222-e230.
Musumeci, G.; Trovato, F.M.; Pichler, K.; Weinberg, A.M.; Loreto, C.; Castrogiovanni, P. Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: An in vivo and in vitro study on lubricin expression. J. Nutr. Biochem., 2013, 24(12), 2064-2075.
Szychlinska, M.A.; Castrogiovanni, P.; Trovato, F.M.; Nsir, H.; Zarrouk, M.; Lo Furno, D.; Di Rosa, M.; Imbesi, R.; Musumeci, G. Physical activity and mediterranean diet based on olive tree phenolic compounds from two different geographical areas have protective effects on early osteoarthritis, muscle atrophy and hepatic steatosis. Eur. J. Nutr., 2018.
Omata, S.; Sonokawa, S.; Sawae, Y.; Murakami, T. Effects of both vitamin c and mechanical stimulation on improving the mechanical characteristics of regenerated cartilage. Biochem. Biophys. Res. Commun., 2012, 424(4), 724-729.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [32 - 46]
Pages: 15
DOI: 10.2174/1389201020666190206202048
Price: $58

Article Metrics

PDF: 23
PRC: 2