Influence of Polycaprolactone and Basic Fibroblast Growth Factor on Gingival Fibroblasts

Guided tissue regeneration (GTR) to regenerate periodontal tissue involves placement of a cell-occlusive barrier membrane functionally excluding the gingiva and associated oral epithelium from the periodontal defect. Gingival connective tissue (CT) contains a rich vascular plexus and is a source of progenitor cells which could contribute to periodontal regeneration. We propose the use of a novel biodegradable and bioactive electrospun fibrous polycaprolactone (PCL) scaffold loaded with microspheres releasing basic fibroblast growth factor (bFGF) to promote gingival CT growth while maintaining a barrier to the oral epithelium. Scaffolds supported human gingival fibroblast proliferation and mesenchymal cell infiltration in a bFGF dose dependent manner. Oral epithelial cells were excluded from the interior of the scaffolds. Scaffold treatment during early healing of rat gingival wounds showed good biocompatibility. This study suggests that PCL electrospun scaffolds loaded with bFGF microspheres represent a promising alternative to the current generation of GTR barrier membranes

Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in intact human gingival connective tissue ex vivo

Drug-induced gingival enlargement (DIGE) is a fibrotic condition that can be caused by the antihypertensive drug nifedipine and the anti-seizure drug phenytoin, but the molecular etiology of this type of fibrosis is not well understood and the role of confounding factors such as inflammation remains to be fully investigated. The aim of this study was to develop an ex vivo gingival explant system to allow investigation of the effects of nifedipine and phenytoin alone on human gingival tissue. Comparisons were made to the histology of human DIGE tissue retrieved from individuals with DIGE. Increased collagen, fibronectin, and proliferating fibroblasts were evident, but myofibroblasts were not detected in DIGE samples caused by nifedipine and phenytoin. In healthy gingiva cultured in nifedipine or phenytoin-containing media, the number of cells positive for p-SMAD2/3 increased, concomitant with increased CCN2 and periostin immunoreactivity compared to untreated explants. Collagen content assessed through hydroxyproline assays was significantly higher in tissues cultured with either drug compared to control tissues, which was confirmed histologically. Matrix fibronectin levels were also qualitatively greater in tissues treated with either drug. No significant differences in proliferating cells were observed between any of the conditions. Our study demonstrates that nifedipine and phenytoin activate canonical transforming growth factor-beta signaling, CCN2 and periostin expression, as well as increase collagen density, but do not influence cell proliferation or induce myofibroblast differentiation. We conclude that in the absence of confounding variables, nifedipine and phenytoin alter matrix homeostasis in gingival tissue explants ex vivo, and drug administration is a significant factor influencing ECM accumulation in gingival enlargement

Periostin and CCN2 Scaffolds Promote the Wound Healing Response in the Skin of Diabetic Mice

© 2019, Mary Ann Liebert, Inc., publishers 2019. Impaired skin wounds represent a significant and growing complication associated with type II diabetes and effective clinical strategies to reproducibly induce wound resolution do not exist. As a class of secreted nonstructural matrix proteins that modulate many cellular aspects of skin healing, matricellular proteins could represent a novel mechanism to promote skin healing. Based on their role in the regulation of the proliferative phase of healing, we hypothesized that local delivery of periostin and CCN2 could suppress inflammation and progress wounds into the proliferative and remodeling phases of repair. Using electrospinning, scaffolds composed of collagen type I and periostin or CCN2 were fabricated. Delivery of periostin/collagen and CCN2/collagen electrospun scaffolds increased excisional wound closure rates in a murine db/db diabetic model compared with collagen alone or untreated wounds. Reduced neutrophil infiltration was evident in the presence of periostin/collagen and CCN2/collagen scaffolds, concomitant with an increase in mesenchymal cell infiltration versus empty and collagen scaffolds alone at day 7. Microarray analysis demonstrated scaffold-dependent upregulation of gene clusters associated with wound contraction, cell differentiation, and suppression of PPARγsignaling at day 7; however, no changes in mRNA levels of extracellular matrix genes were observed compared with controls. At day 11, significantly increased vascularization of the wound bed was evident. Local delivery of periostin- and CCN2-based biomaterials may represent a novel strategy to induce the proliferative phase of repair and correction of the healing process in impaired skin wounds. Nonhealing skin wounds remain a significant burden on health care systems, with diabetic patients 20 times as likely to undergo a lower extremity amputation due to impaired healing. Novel treatments that suppress the proinflammatory signature and induce the proliferative and remodeling phases are needed clinically. We demonstrate that the addition of periostin and CCN2 in a scaffold form increases closure rates of full-thickness skin wounds in diabetic mice, concomitant with enhanced angiogenesis. Our results demonstrate the efficacy of periostin- and CCN2-containing biomaterials to stimulate wound closure, which could represent a novel method for the treatment of diabetic skin wounds