^{Thermosensitive Poly(N-vinylcaprolactam) Injectable Hydrogels for Cartilage Tissue Engineering}

Abstract

Injectable hydrogels have gained prominence in the field of tissue engineering for minimally invasive delivery of cells for tissue repair and in the filling of irregular defects. However, many injectable hydrogels exhibit long gelation times or are not stable for long periods after injection. To address these concerns, we used thermosensitive poly(N-vinylcaprolactam) (PNVCL) hydrogels due to their cytocompatibility and fast response to temperature stimuli. Changes in the PNVCL molecular weight and concentration enabled the development of hydrogels with tunable mechanical properties and fast gelation times (<60 s when the temperature was raised from room temperature to physiologic temperature). Chondrocytes (CHs) and mesenchymal stem cells were encapsulated in PNVCL hydrogels and exhibited high viability (∼90%), as monitored by Live/Dead staining and Alamar Blue assays. Three-dimensional constructs of CH-laden PNVCL hydrogels supported cartilage-specific extracellular matrix production both in vitro and after subcutaneous injection in nude rats for up to 8 weeks. Moreover, biochemical analyses of constructs demonstrated a time-dependent increase in glycosaminoglycans (GAGs) and collagen, which were significantly augmented in the implants cultured in vivo. Histological analyses also demonstrated regular distribution of synthesized cartilage components, including abundant GAGs and type II collagen. The findings from this study demonstrate thermosensitive PNVCL as a candidate injectable biomaterial to deliver cells for cartilage tissue engineering.

Advanced hydrogels for the repair of cartilage defects and regeneration

“…Apart from mechanical properties, synthetic polymers can have versatile functions. Poly(N-vinylcaprolactam) (PVCL) is a cytocompatible thermosensitive polymer that can be used to fabricate injectable hydrogels for cartilage tissue engineering [ 42 , 43 ]. Sala et al showed chondrocytes and MSCs exhibited high viability in PVCL hydrogels [ 42 ].…”

“…Poly(N-vinylcaprolactam) (PVCL) is a cytocompatible thermosensitive polymer that can be used to fabricate injectable hydrogels for cartilage tissue engineering [ 42 , 43 ]. Sala et al showed chondrocytes and MSCs exhibited high viability in PVCL hydrogels [ 42 ]. Both in vitro and in vivo tests showed that cartilage-specific extracellular matrix (ECM) was produced in a chondrocytes-laden PVCL hydrogel.…”

Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis

“…The biorthogonal dPGS-PEG hydrogel demonstrated an elastic modulus varying from 1 to 5 kPa by varying the dPGS content and maintained higher cell viability with tissue formation [ 108 ]. PNVCL hydrogels were investigated because of their thermoresponsive in situ gelling properties, showing a LCST value similar to the physiological temperature [ 109 ]. Furthermore, to take advantage of the elastic and biodegradable properties of PEU, hydrogel scaffolds with different pore sizes of 200, 400, and 600 µm and Young’s moduli of 16 ± 3, 7 ± 1, 5.6 ± 0.5 MPa were developed [ 110 ].…”

Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue Regeneration

“…These macromers are particularly promising for cell encapsulation applications, as they facilitate biointegration and degradation via hydrolysis of the phosphate ester bonds of MAEP. [128] Similar to pNIPAm, are the elastin-like polypeptides (ELPs) with a sol-gel transition at 34 °C, first reported by Urry et al [129] Different cell encapsulation systems using ELPs have been recently described elsewhere. Hydrogels that readily undergo enzymatic degradation have demonstrated improved bone growth and infiltration.…”