In this study, by implanting DDM combined with PDRN into the subcutaneous soft tissue of nude mice, we could confirm that bone-forming cells were supplemented and differentiated into osteoblast around graft materials, and then new bone was formed. In other words, we could confirm osteoinduction which induced bone formation. As for the substances showing such osteoinduction, there are bone morphogenetic proteins (BMPs), platelet-derived growth factors (PDGF), insulin-like growth factors (IGF), fibroblast growth factors (FGF), epidermal growth factors (EGF), transforming growth factor or tumor growth factor (TGF), retinoic acid, etc. . Of these, BMP in particular is widely known to induce bone-forming cells when it is implanted into the subcutaneous areas without the bone or under muscles, and its excellent effect in experiments and clinical settings has already been proved in oral and maxillofacial field .
Meanwhile, the PDRN used in this study was an activation component which was included in the materials used for healing of cuts and skin regeneration and was composed of parts of low molecular DNA. As purine and pyrimidine nucleotides are formed as a polymer of deoxyribonucleotides which are composed of 50~2000 bases with a combined form via phosphodiester combination, they supply purine and pyrimidine as well as deoxyribonucleotides and deoxyribonucleosides . It is reported that as for PDRN, nucleotides and ne growth of various shapes of cells, synthesis of nucleic acid and healing of cuts [12, 13], salvage pathways to create nucleic acid with low energy consumption [14, 15], and activate A2 purinergic receptors . Also, other reports state that it has an effect on chronic cuts and burns [17, 18].
With many recent studies highlighting the importance of extracellular nucleotides and nucleosides which newly stimulate cell growth, Guizzardi et al.  reported that PDRN stimulated fibroblast and collagen by stimulating the aforementioned purinergic receptor system. They evaluated the effect of PDRN in human osteoblast cultured in an experiment and confirmed that PDRN promoted cell growth through the result that a high increase of growth of osteoblast in a PDRN-administered group compared to a control group was seen in their experiment focusing on cell division and alkaline phosphatase activity. In particular, although PDRN-treated cells showed low phosphate activity in the result of the sixth day compared to the control group, alkaline phosphatase activity was shown to gradually increase from the experiment starting day to the 10th day overall, and from these data, PDRN was proved to work as an osteoblast growth stimulant. Sini et al.  investigated the effect of Oligo-composite and PDRN on growth and protein secretion of cultured human skin fibroblast and reported that both PDRN and DNAse-treated PDRN promoted the growth of cultured human fibroblast. Also, the cells cultured with PDRN were shown to promote the synthesis and secretion of protein. Thellung et al.  confirmed that PDRN and adenosine increased the growth rate of human skin fibroblast in primary culture and reported that PDRN worked as a pro-drug which provided a sufficient amount of mitogenic deoxyribonucleotides, deoxyribonucleosides, and base to cultured cells.
According to these study results, we could confirm that activation of the A2 receptor subtype purinergic receptor through the agency of PDRN promoted propagation of cells and tissue restoration, and it is considered that the function of PDRN as tissue regeneration and medicine is very positive and it can also be applied to the bone defects in the oral and maxillofacial surgical field.
The PDRN used in this study was a material which had been approved and used as a local treatment agent and parenteral medicine in Italy and is known to be effective for leg ulcers, burns, and depressed scars . However, PDRN is liquid phase, and this study needed a scaffold where cells could be attached, grow, and differentiate in the cell differentiation of PDRN to investigate bone-forming capacity, a hard tissue, while previous studies focused on wound healing and regeneration of soft tissue. Therefore, the author, et al., used DDM as a scaffold. As DDM was already proved to have osteoinduction in itself, has little foreign body reaction, and can emit growth factors in a sustained-release (SR) manner due to its porous microstructure. In addition, as it can maintain the shape of an implant site and play the role of structurally reinforcing defects to prevent the twist of neighboring tissue, it can be regarded as an ideal scaffold [2, 3].
The author, et al., could observe bone-forming cells and the expression of new bone through a histological observation of PDRN and DDM implanted into the soft issue of nude mice and looked into the osteoinduction of PDRN and the possibility of DDM as an ideal carrier in a histological and histomorphometric way. In particular, taking a short period, 4 weeks after graft and implant into soft tissue, not hard tissue, into consideration, the hardness of new bone was observed to have advanced considerably. In addition, as the new growing blood vessels entered, absorption of DDM particles were observed, and so it can be considered that DDM plays the role of an ideal scaffold as DDM is slowly absorbed, maintaining the space, and replaced by new bone.
However, the limitations present in this study include failures to verify statistical significance due to a lack of samples in the histomorphometric analysis and to set control group as carrier.