## 1 Introduction  
Periodontitis is a pathological condition characterized by inflammation arising from the intricate interaction between the bacterial microbiota and the human immune response, which is frequently influenced by behavioral variables [1]. The aim of periodontal therapy is to control periodontal tissue inflammation, while the ideal goal is to regenerate the periodontal tissue that has been lost as a consequence of destruction caused by periodontitis or traumatic injury [2]. The biological concept of potentially regenerating various tissue components as a part of the healing process following periodontal surgery was introduced early in the 1980s [3]. Clinical application of guided periodontal tissue regeneration is based on the principle of using a physical barrier membrane to shield the affected area from undesirable tissue ingrowth, while guiding the repopulation of periodontal and bone cells [2; 4]. Not all regenerative procedures are associated with the same level of clinical efficacy. Several factors, including patient and surgical factors, influence clinical outcomes [2]. At least 20% of etiological factors for periodontal tissue destruction can be attributed to tobacco use [5]. Therefore, smoking is recognized as a risk factor in the periodontitis grading system [6; 7]. The direct suppression of normal fibroblast function may be responsible for a variety of underlying effects of tobacco products on periodontal tissues [8]. On the other hand, the surgical factor with a critical effect on the outcome of the tissue regeneration procedure involves the proper selection of the barrier membrane [9]. Bioabsorbable membranes comprising type I bovine or porcine collagen or poly(hydroxy acids), such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and their co-polymers, are predominantly utilized in periodontal regeneration [10]. Biocompatibility with periodontal cells (particularly gingival fibroblasts) plays an important role if the membrane is exposed to the oral environment, which presents many challenges during the regeneration process [11]. BioMend(r), made from glutaraldehyde-crosslinked bovine type I collagen, is one of the most commonly used collagen membranes [12]. Another commonly used, but non-crosslinked, bioabsorbable membrane is CopiOs(r) Pericardium, which is composed of pericardium-derived collagen types I and III. Different strategies to promote regeneration of periodontal defects have been developed. Expanding the functions of these membranes as not only barriers but also delivery devices for various agents, such as anti-oxidants, is a recently introduced approach [13]. The role of antioxidants in overall health, and particularly in the health of oral hard and soft tissues, is well established in the literature [14], and there is evidence that antioxidant supplements are necessary for the successful prevention and treatment of disease, including gingival and periodontal diseases [15; 16; 17]. Vitamin C, as a water-soluble and potent reducing agent, is an effective antioxidant that has been shown to regulate the procollagen gene's expression, which impacts both collagen synthesis and fibroblast transformation [18]. It has been demonstrated that vitamin C alters the epigenetic/gene expression profile and extracellular matrix (microenvironment) of human cells [15]. In addition, this vitamin stimulates the osteoblasts' growth, metabolism, differentiation, and morphogenesis [19]. Vitamin C has been suggested as a supplement capable of reducing the negative effects of toxic compounds in tobacco smoke, as it protects the aqueous components of cells (particularly the cytoplasm) against oxidative reactions and free radicals [20]. Vitamin C, when administered systemically, locally, or both, reverses the negative effects of nicotine and cotinine on human gingival fibroblasts [20; 21; 22].