A novel composition for in vitro and in vivo regeneration of skin and connective tissues

Abstract

The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses.

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A2A Receptor Involvement

“…As observed in Figures and , the 20 skin regeneration studies were: (1) six in vitro studies on skin fibroblasts (FBs) or biopsies (Muratore et al, ; Sini et al, ; Thellung et al, ; Belletti et al, ; Pleshkanyova et al, ; Avantaggiato et al, ); (2) six in vivo studies in animal models of thermal injuries (Bitto et al, ), back skin or ischemic flap (Polito et al, ; Chung et al, ; Lee et al, ), and back full‐thickness incisions (Galeano et al, ; Altavilla et al, ) in diabetic or healthy animals; (3) in healthy or diabetic patients affected by ulcers (Kim et al, ; Squadrito et al, ; De Caridi et al, ), benign cervical lesions (Perino et al, ) or subjected to autologous skin grafts (Rubegni et al, ; De Aloe et al, ; Valdatta et al, ) (seven clinical studies). In addition, one study included in vitro and an in vivo parts regarding the effects of PDRNs in biopsies from foot ulcers of diabetic patients and back full‐thickness wounds of diabetic mice (Gennero et al, ).…”

“…The same conclusions were also reached in two other in vivo studies, conducted in genetically diabetic mice with incisions of the dorsum, where PDRN amount and way of administration were the same as the four previous ones (Galeano et al, ; Altavilla et al, ). One study, performed both in vitro, in biopsies of ulcers of diabetic patients, and in vivo in diabetic mice with back incisions, observed that the application of a cream or the infusion of PDRNs combined with l ‐carnitine, Ca ions, proteolytic enzymes and antioxidant agents increased cell viability, ECM protein production, healing, re‐epithelialization rate, and reduced MMP production (Gennero et al, ).…”

“…In vitro studies, conducted with FBs or skin biopsies, demonstrated a trophic and anti‐inflammatory effect of PDRNs, observing an improvement in FB growth, ECM protein production (FBN and collagens), and DNA damage repair with a concomitant reduction in MMP expression and cell apoptosis. Even if different PDRN dosages were evaluated, the authors agreed a dose‐response effect of PDRNs up to 100 μg/ml (Muratore et al, ; Sini et al, ; Thellung et al, ; Belletti et al, ; Pleshkanyova et al, ; Gennero et al, ; Avantaggiato et al, ). In all in vivo studies, the amount and the way of administration were the same, 8 mg/kg in 100 μl of vehicle solution by intraperitoneal injection (Bitto et al, ; Galeano et al, ; Altavilla et al, ; Polito et al, ; Chung et al, ; Lee et al, ) and only one study employed PDRNs in the form of cream (Gennero et al, ).…”

Localization of Human Mesenchymal Stem Cells from Umbilical Cord Blood and Their Role in Repair of Diabetic Foot Ulcers in Rats

“…The highest expression of CK19 is in fetal basal epidermal cells and the lowest, almost negative, expression is in adults 33. CK19 is expressed in epidermal stem cells, but as the epidermal cells differentiate, the expression of CK19 is reduced and replaced by other CKs.…”

Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration

“…Ideally, in the remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis (Gennero et al 2011). However, pathological remodeling, such as scar formation, is often observed in various skin wounds.…”