Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing

Abstract

In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing.

Time-dependent effects of cellulose and gelatin-based hemostats on cellular processes of wound healing

“…*p < 0.05 vs. control; **p < 0.05 vs. control and GELA; ***p < 0.05 vs. control, GELA and ORC. Two-way ANOVA with 2-stage step-up method of Benjamini, Krieger and Yekutieli was applied (q = 0.05, n = 5-7/experimental group) to the absence of buffer-acting serum components [26,27]. Consistent with previous findings, this study found that ONRC caused the strongest decline of pH values during degradation, as frayed and less condensed fibers form a larger surface area, leading to more rapid release of acidic groups [27].…”

“…Two-way ANOVA with 2-stage step-up method of Benjamini, Krieger and Yekutieli was applied (q = 0.05, n = 5-7/experimental group) to the absence of buffer-acting serum components [26,27]. Consistent with previous findings, this study found that ONRC caused the strongest decline of pH values during degradation, as frayed and less condensed fibers form a larger surface area, leading to more rapid release of acidic groups [27]. In contrast, GELA proved to be pH neutral and maintained prolonged structural integrity over 24 h. Our findings seem plausible, since reported time frames for complete degradation in vivo vary from 14 days up to 5 weeks for CBH, while the same process may take as long as 4-6 weeks for GBH and may be accelerated und standardized in in vitro conditions [28][29][30].…”

Impact of Source and Manufacturing of Collagen Matrices on Fibroblast Cell Growth and Platelet Aggregation

“…This effect can be attributed to the ORC fraction of the product Promogran. A drop in pH level was described for oxidized cellulose hemostatic agents, although some authors describe differences between investigated media types [ 40 , 41 ]. The shift to a more acidic value might on the one hand occur by degradation, as the depolymerization leads to the release of acidic groups [ 42 ].…”

Bleeding in Dental Surgery

“…Despite the beneficial effect of these local hemostatic agents in preventing bleeding in dental surgery, available data comparing their effectiveness and efficiency is still scarce and inconclusive. Methodological heterogeneities, such as the lack of a standard therapy and comparable treatment regimens, are noticeable among studies, as well as the reduced number of randomized controlled trials [2,[56][57][58][59][60][61][62][63][64][65][66][67][68][69][70].…”