3.4 Application of Injectable Smart Materials for Tissue Repair and Regeneration
3.4.2 Cartilage
as an avascular and aneural tissue, articular cartilage shows limited self-healing capabilities.67 in the case of a large-area cartilage defect, there are no effective approaches currently to completely restore injured articular cartilage in terms of morphological, biochemical, and biomechanical char- acteristics.68 Currently, a strategy based on tissue engineering offers prom- ise for cartilage repair and regeneration, in which chondrogenic cells are transplanted into a defect site through encapsulating them into an inject- able hydrogel (table 3.1).3
injectable hydrogels also show particular advantages for the treatment of degenerative disc disease, because they could fill a degenerate area perfectly,
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00067
Chapter 376 Table 3.1 examples of injectable smart hydrogels used in cartilage tissue engineering.
Materials Stimuli Cell type application references
Chitosan/β-glycerophosphate/
hydroxyethyl cellulose thermal Mesenchymal stem cells
(MSCs) the Ch–gp–heC hydrogel provided suitable condi- tions for chondrogenic differentiation in vivo 82 glycopolypeptide enzyme rabbit chondrocytes Cells maintained chondrocyte phenotype and
produced the cartilaginous specific matrix in a subcutaneous model of nude mice
83
Chitosan/gelatin/hyaluronic acid (ha)/β-tricalcium phosphate
thermal Cell-free In vivo formed hydrogel induced minimal invasion of
inflammatory cells 84
Copolymer of pnipaam and
peg thermal Cell-free it is possible to restore angular stiffness to a cyclically fatigued spinal segment using an injectable hydro- gel as a nucleus replacement
85
poly(N-isopropylacrylamide)- g-methylcellulose
(pnipaam-g-MC)
thermal atDC5 cells (murine
chondrogenic cell line) pnipaam-g-MC did not affect the cell viability and proliferation, and synthesis of glycosoaminogly- cans was increased
86
Chitosan–pluronic (Cp) thermal Bovine chondrocytes the proliferation of cells and the amount of synthe- sized glycosaminoglycan increased for 28 days 9 pluronic F-127 thermal autologous porcine
auricular chondrocytes injection of autologous porcine auricular chondro- cytes suspended in hydrogel resulted in the forma- tion of cartilage tissue in the approximate size and shape of a human ear helix
87
poly(N-isopropylacrylamide)- g-chondroitinsulfate (pnipaam-g-CS)
thermal Cell-free the mechanical properties, bioadhesive strength, and cytocompatibility satisfy for nucleus pulposus (np) regeneration
76
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00067
77Applications of Injectable Smart Materials in Tissue Engineering Chitosan/β-glycerol
phosphate (gp) thermal primary calfarticular
chondrocytes hydrogel can support in vitro and in vivo accumula- tion of cartilage matrix by primary chondrocytes, while persisting in osteochondral defects in vivo
88
Chitosan/β-
gp/ hydroxyethylcellulose (heC)
thermal — Chitosan-gp/heC is suitable for clinical orthopedic applications involving single use treatments that guide acute cartilage repair processes
89
Chitosan/β-gp/
hydroxyethylcellulose (heC)
thermal Sheep chondrocytes the hydrogel could support the matrix accumulation of chondrocytes cultured in vitro and could repair sheep cartilage defects in 24 weeks
90
Chitosan/gelatin/β-gp thermal nucleus pulposus (np)
cells gelatin added into β-gp hydrogel significantly short- ened the gelation time and improved gel strength without influencing the biocompatibility
91
Chitosan-graft-poly(N-
isopropylacrylamide) thermal Chondrocytes and
meniscus cells the hydrogel preserved the viability and phenotypic morphology of the entrapped cells, and stimulated the initial cell–cell interactions
92
pnipaam-g-CS (chondroitin
sulfate) thermal — the encapsulation of alginate microparticles within
pnipaam-g-CS gels exhibited increased adhe- sive strength with tissue, and did not induce cytotoxicity
93
hyaluronic acid (ha)/pluronic
F127 thermal Mesenchymal stromal
cells (MSCs) In vivo chondrogenic potential of MSCs could be affected by dexamethasone (Dex) released from microspheres encapsulated in the hydrogel
94
poly(N-substituted
α/β-asparagine) thermal rabbit chondrocytes the polymers demonstrated a concentration-depen- dent inhibitory effect on the chondrocytes' sur- vival. over 70% of the chondrocytes could survive through the physical and/or chemical stress
95
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00067
and thus minimize surgical defects. in addition, hydrogels can reduce the risk of implant migration and subsequent loss of height of the intervertebral disc.69,70 the load-bearing biomechanical function of the intervertebral disc is determined by the composition and organization of the extracellular matrix (eCM) components, collagen and aggrecan. the major role of aggrecan is to maintain tissue hydration, and hence maintain disc height under the high loads imposed by body weight and muscle activity.71 Due to this important role, glycosaminoglycan from native eCM, including hyaluronic acid (ha)72 and chondroitin sulfate (CS), has been utilized for the construction of hydro- gel systems for nucleus pulposus (np) regeneration (table 3.1).73–81
in addition to polymers, peptide-based supramolecular hydrogels have also been utilized for cartilage regeneration. an injectable hydrogel based on self-assembling peptide (KLD) was evaluated for its ability to stimulate regeneration of the cartilage in a rabbit model of a full-thickness, critical- ly-sized, cartilage defect. addition of chondrogenic factors and bone marrow stromal cells remarkably reduced the quality of repair and enhanced osteo- phyte formation compared to a KLD control after 12 weeks.96
Matsuda and ito reported a novel shear-sensitive hydrogel, which formed by supramolecular self-assembly between pDZ domain-containing fusion pro- tein, and a pDZ domain-recognizable peptide, which was covalently linked to the terminal groups of four-armed poly(ethylene glycol). it demonstrated shear stress-dependent reversible-phase transformation. a spontaneous viscoelastic hydrogel was formed at low shear stress, but it was transformed into a sol at high shear stress. this shear-sensitive hydrogel shows potential for use as an injectable cell delivery system for cartilage repair and regeneration.97
Ma et al. developed a supramolecular hydrogel with shear-thinning and self-integrating properties, and evaluated the potential for cartilage–bone tissue regeneration in a subcutaneous implantation model of nude mice (Figure 3.5).
the regeneration of the cartilage–bone tissue complex was successfully realized by using the self-integrating hydrogel with selected cells and biomolecules.98