Establishment and verification of a mouse model of nasal wound healing

Abstract

Objectives Poor wound healing as reflected by the development of synechia and osteitis after endoscopic sinus surgery may trigger disease recurrence. Animal models provide insights into the pathogenesis of poor wound healing and may aid in the development of new therapeutics. Here, we established a mouse model of nasal wound healing and confirmed its utility. Study Design Animal study. Methods Unilateral intranasal wounds were induced using a small interdental brush in 6‐week‐old C57BL/6 mice. Forty‐five mice were divided into three groups (each n = 15): one control and two experimental groups (intranasal vs. intraperitoneal dexamethasone). Mice were sacrificed on days 2, 14, and 28 after injury (each n = 5). Serial changes in nasal wound histopathology were described, and intergroup differences were analyzed. Results On day 2, mucosal detachment, hemorrhage, and exudate were observed. On day 14, synechiae featuring neo‐osteogenesis (bone lacunae, osteoblasts, and multinucleated osteoclasts) between the septum and the maxilloturbinate were prominent, followed by wound maturation on day 28: fewer lacunae and smaller osteoblasts. Macrophages were evident only on day 2, and lymphocytes were predominant on day 28. The amount of exudate on day 2 and the synechial area on day 28 were significantly reduced in mice that received dexamethasone systemically compared with control mice, with similar trends in those treated intranasally. Conclusion Our mouse model of nasal wound healing was characterized by the development of bony synechia and neo‐osteogenesis, not soft‐tissue synechia. The model may be useful in the assessment of novel therapeutics to prevent those wounds. Level of Evidence NALaryngoscope, 129:E266–E271, 2019

The Impact of Spray Cryotherapy on Lesion-Induced Osteitis in a New Murine Experimental Model

“…To investigate the specific role of sino-nasal inflammation in bone remodeling associated with rhinosinusitis and the relationship between mucosal denudation and subsequent subjacent osteitis, we conducted our experimental models following the model proposed by Joo et al, 2019 [ 26 ]. Joo et al describe the first experimental model on wound healing of small animals featuring exposed bone and neo-osteogenesis.…”

Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity

“…and enhances overall wound healing process [20], there is only limited information about the most effective concentration and duration of the treatment. Since release kinetics are highly dependent on the ratio between lactic acid and glycolic acid in PLGA as well as the pH conditions [33], we could finely tune the release profile considering the preferred maintenance of the Dex concentration in the nasal inflammatory environment.…”

“…We selected Dex as a model corticoid drug because it was reported to repress the expression of many inflammatory cytokines and has a therapeutic effect on the wound healing process after the surgical procedure [ 6 , 14 , 20 ]. To encapsulate Dex into the PLGA microparticles, we used a single oil-in-water emulsion/evaporation method [ 16 , 22 ].…”

“…As for the materials, the Dex release kinetics should be further optimized for better efficacy for the treatment of postoperative osteitis. Although it is known that topical steroid administration gives significant effects in the early postoperative period, as it can minimize the mucosa inflammation, synechia and other complications, and enhances overall wound healing process [ 20 ], there is only limited information about the most effective concentration and duration of the treatment. Since release kinetics are highly dependent on the ratio between lactic acid and glycolic acid in PLGA as well as the pH conditions [ 33 ], we could finely tune the release profile considering the preferred maintenance of the Dex concentration in the nasal inflammatory environment.…”

“…PBMP contains both phosphomonoester groups for calcium binding and butyl groups for hydrophobic PLGA binding, respectively, and can be coated on the hydrophobic surface of PLGA microparticles to introduce an adhesive property on calcium-rich tissues. We selected dexamethasone (Dex) as a model corticoid drug, which can reduce the inflammatory sinonasal mucosa [ 19 ] and promote wound repair following the surgical procedure [ 20 ]. We intended to maintain the Dex concentration for a longer duration only near the exposed bones after the surgery through sustained Dex release from the PLGA/PBMP particles, which have a specific binding affinity to the calcium-rich tissues ( Figure 1 ).…”