Neutrophils exhibit distinct phenotypes toward chitosans with different degrees of deacetylation: implications for cartilage repair

Abstract

Introduction Osteoarthritis is characterized by the progressive destruction of cartilage in the articular joints. Novel therapies that promote resurfacing of exposed bone in focal areas are of interest in osteoarthritis because they may delay the progression of this disabling disease in patients who develop focal lesions. Recently, the addition of 80% deacetylated chitosan to cartilage microfractures was shown to promote the regeneration of hyaline cartilage. The molecular mechanisms by which chitosan promotes cartilage regeneration remain unknown. Because neutrophils are transiently recruited to the microfracture site, the effect of 80% deacetylated chitosan on the function of neutrophils was investigated. Most studies on neutrophils use preparations of chitosan with an uncertain degree of deacetylation. For therapeutic purposes, it is of interest to determine whether the degree of deacetylation influences the response of neutrophils to chitosan. The effect of 95% deacetylated chitosan on the function of neutrophils was therefore also investigated and compared with that of 80% deacetylated chitosan.

Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

“…Biodegradable chitosan is known to elicit neutrophils via a leukotriene B4-sensitive pathway, while promoting an anti-inflammatory phenotype as chitosan-stimulated neutrophils release neither superoxide nor myeloperoxidase [25]. Previous chitosan-induced cartilage repair studies in rabbits have documented neutrophil chemotaxis at 21 days that is associated with a delay in matrix deposition, as observed in the current study [9,26].…”

Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein

“…The in vivo tissue response to chitosan depends on several factors such as the degree of deacetylation, cross-linking chemistry and the molecular weight [18,24]. A significant difference in the in vivo behavior of 95 % deacetylated and 80 % de-acetylated chitosan was observed wherein, the 80 % showed phospholipase-A2-derived bioactive lipid mediated chemotactic activity towards neutrophils [25]. The present study investigated the in vivo local tissue response to thermogels developed from *75 % deacetylated chitosan and its efficacy to retain the bioactivity of encapsulated rhBMP2.…”

“…Azab et al [18] using glutaraldehyde cross-linked chitosan showed a very mild tissue response, with the absence of neutrophils after 1 week of implantation. On the other hand, several studies have demonstrated the persistent presence of neutrophils in chitosan scaffolds [24,25,29]. Since neutrophilic enzymes such as lyzozymes are involved in the degradation of chitosan, it is presumed that neutrophil infiltration will significantly increase the degradation of the matrix [30].…”

“…Since neutrophilic enzymes such as lyzozymes are involved in the degradation of chitosan, it is presumed that neutrophil infiltration will significantly increase the degradation of the matrix [30]. Simard et al [25] has demonstrated that neutrophils exhibit different phenotypes towards chitosans of different degree of deacetylation, which might have implications on chitosan degradation as well as promoting wound repair. The efficacy of chitosan (74-78 % deacetylated)-AHP thermogels in modulating the immune cell functions are currently under investigation.…”

Chitosan as a starting material for wound healing applications

“…It was shown that chitosan is involved in all stages of wound healing. During the initial healing phases, chitosan shows its unique hemostatic properties and promotes infiltration and migration of neutrophils and macrophages (Park et al, 2009;Simard et al, 2009). Thereby wounds are cleaned from foreign agents and granulation tissue is formed allowing fibrous tissue formation and re-epithelialization.…”