Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model

Abstract

Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel for cartilage repair obtained by covalently grafting poly(N-isopropylacrylamide) to hyaluronan, to give a brush co-polymer HpN. The gel is fluid at room temperature and becomes gel at body temperature. In this pilot study HpN safety and repair response were evaluated in an osteochondral defect model in rabbit. Follow-up was of 1 week and 12 weeks and the empty defect served as a control, for a total of four experimental groups. At 12 weeks the defect sites were evaluated macroscopically and histologically. Local lymph nodes, spleen, liver, and kidneys were analyzed for histopathological evaluation. HpN could be easily injected and remained into the defect throughout the study. The macroscopic score was statistically superior for HpN versus empty. Histological score gave opposite trend but not statistically significant. A slight tissue reaction was observed around HpN, however, vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with fairly good continuity and lateral integration into the existing articular cartilage was observed in all cases. No signs of local or systemic acute or subacute toxicity were observed. In conclusion, HpN is easily injectable, remains into an osteochondral defect within a moving synovial joint, is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1469-1478, 2016.

Injectable hydrogels and nanocomposite hydrogels for cartilage regeneration

“…64,65 For REVIEW ARTICLE JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2018 VOL 00A, ISSUE 00 example, additional hydrophobic groups resulting from copolymerization lead to lowering of LCST. 65 The most commonly used thermogels in cartilage tissue engineering are PluronicsV R , 66 p(NIPAAm) 67 and chitosan/ glycerol phosphate 68 very often grafted or blended with gelatin, 69 hyaluronic acid, 70 and chitosan. 49 Based on the literature review, it can be seen that common approach is using thermoresponsive base, such as p(NIPAAm) or PluronicV R with addition of natural polymer, such as hyaluronic acid for improvement of cellular response.…”

“…The most commonly used thermogels in cartilage tissue engineering are Pluronics®, p(NIPAAm) and chitosan/glycerol phosphate very often grafted or blended with gelatin, hyaluronic acid, and chitosan . Based on the literature review, it can be seen that common approach is using thermoresponsive base, such as p(NIPAAm) or Pluronic® with addition of natural polymer, such as hyaluronic acid for improvement of cellular response.…”

Bone and cartilage differentiation of a single stem cell population driven by material interface

“…In the study by D’Este et al, 37 biocompatibility and ease of use were confirmed, as the gel was injected into the site of the defect. Gel shearing from the nanotopographical surface could present a potential limitation of this construct upon scaling-up.…”

“…37 The addition of cells to the hydrogel led to a decrease of storage modulus after the transition. This is to be expected because the gelation mechanism is based on non-covalent interactions prone to disruption by the presence of MSC, especially at such a high concentration.…”

“…However, the 2016 study validated retention of the gel in a partially weight-bearing osteochondral defect within a moving synovial joint for up to 12 weeks; it was also noted here that the implanted gels had lost their reversibility upon long-term harvesting. 37 …”