The effect of hypoxia on thermosensitive poly(N -vinylcaprolactam) hydrogels with tunable mechanical integrity for cartilage tissue engineering

Abstract

Cartilage repair presents a daunting challenge in tissue engineering applications due to the low oxygen conditions (hypoxia) affiliated in diseased states. Hence, the use of biomaterial scaffolds with unique variability is imperative to treat diseased or damaged cartilage. Thermosensitive hydrogels show promise as injectable materials that can be used as tissue scaffolds for cartilage tissue regeneration. However, uses in clinical applications are limited to due mechanical stability and therapeutic efficacy to treat diseased tissue. In this study, several composite hydrogels containing poly(N-vinylcaprolactam) (PVCL) and methacrylated hyaluronic acid (meHA) were prepared using free radical polymerization to produce PVCL-graft-HA (PVCL-g-HA) and characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy. Lower critical solution temperatures and gelation temperatures were confirmed in the range of 33-34°C and 41-45°C, respectively. Using dynamic sheer rheology, the temperature dependence of elastic (G') and viscous (G″) modulus between 25°C and 45°C, revealed that PVCL-g-HA hydrogels at 5% (w/v) concentration exhibited the moduli of 7 Pa (G') to 4 Pa (G″). After 10 days at 1% oxygen, collagen production on PVCL-g-HA hydrogels was 153 ± 25 μg/mg (20%) and 106 ± 18 μg/mg showing a 10-fold increase compared to meHA controls. These studies show promise in PVCL-g-HA hydrogels for the treatment of diseased or damaged articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1863-1873, 2017.

Injectable hydrogels and nanocomposite hydrogels for cartilage regeneration

“…Another studied synthetic‐natural hydrogel system was poly( N ‐vinylcaprolactam) (PVCL)‐ g ‐HA. PVCL was used as an alternative thermogel to p(NIPAAm) . Despite suitable LCST around 33°C, their mechanical properties (storage modulus: 7 Pa, loss modulus: 4 Pa) were much lower than moduli of native cartilage.…”

“…Based on the literature review, it can be stated, that mechanical properties are the biggest challenge in the application of hydrogels in cartilage repair. Studied thermogels have properties differing by several orders of magnitude, for example (PVCL)‐ g ‐HA—storage modulus 7 Pa, carboxymethyl chitin: 250 Pa, PEG‐polyalanine: 844 Pa, polyalanine–poloxamer–polyalanine, about 1500 Pa, but still much lower in comparison to native cartilage (human cartilage storage modulus: 32/43 MPa) …”

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 ].…”

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…Polymer molecular weight can affect LCST. Because of its biocompatibility and low cytotoxicity, PVCL is considered an ideal thermoresponsive polymer for biomedical applications [ 97 , 98 , 99 ], particularly when compared to PNIPAM [ 100 , 101 , 102 ]. PVCL conjugation with hydrophilic units such as PEG or derivatives of PEG enables the synthesis of temperature-responsive block copolymers.…”