ABSTRACT
The formation of a dense fibrous capsule around the foreign body and its contracture is the most common complication of biomaterial implantation. The aim of our research is to find out how the surface of the implant influences the inflammatory and fibrotic reactions in the surrounding tissues. We made three types of implants with a remote surface topography formed of polylactide granules with different diameters: large (100-200 µm), medium (56-100 µm) and small (1-56 µm). We placed these implants in skin pockets in the ears of six chinchilla rabbits. We explanted the implants on the 7th, 14th, 30th and 60th days and performed optical coherence tomography, and histological, immunohistochemical and morphometric studies. We examined 72 samples and compared the composition of immune cell infiltration, vascularization, the thickness of the peri-implant tissues, the severity of fibrotic processes and α-SMA expression in myofibroblasts. We analyzed the scattering coefficient of tissue layers on OCT scans. We found that implants made from large granules induced a milder inflammatory process and slower formation of a connective tissue capsule around the foreign body. Our results prove the importance of assessing the surface texture in order to avoid the formation of capsular contracture after implantation.
ABSTRACT
Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA0) and PLA0 with an equivalent single-dose PF injection performed on POD0 (PLA0+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in PLA@PF and PLA0+injPF groups vs. PLA0. On POD60, PIF was significantly reduced in PLA@PF group. The peri-implant tissue thickness decreased (532 ± 98 µm vs. >1100 µm in control groups) approaching the intact derma thickness value (302 ± 15 µm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS.
ABSTRACT
Mature hypertrophic scars (HSs) remain a challenging clinical problem, particularly due to the absence of biologically relevant experimental models as a standard rabbit ear HS model only reflects an early stage of scarring. The current study aims to adapt this animal model for simulation of mature HS by validating the time of the scar stabilization using qualitative and quantitative criteria. The full-thickness skin and perichondrium excision wounds were created on the ventral side of the rabbit ears. The tissue samples were studied on post-operation days (PODs) 30, 60, 90 and 120. The histopathological examination and morphometry were applied in parallel with biochemical analysis of protein and glycosaminoglycans (GAGs) content and amino acid composition. The supramolecular organization of collagen was explored by differential scanning calorimetry. Four stages of the rabbit ear HS maturation were delineated and attributed with the histolomorphometrical and physicochemical parameters of the tissue. The experimental scars formed in 30 days but stabilized structurally and biochemically only on POD 90-120. This evidence-based model can be used for the studies and testing of new treatments of the mature HSs.