The effect of combination therapy on critical-size bone defects using non-activated platelet-rich plasma and adipose-derived stem cells



Non-activated platelet-rich plasma (nPRP) slowly releases growth factors that induce bone regeneration. Adipose tissue-derived stem cells (ASCs) are also known to induce osteoblast differentiation. In this study, we investigated the combined effect of nPRP and ASC treatment compared with single therapy on bone regeneration.


Thirty New Zealand white rabbits with 15 × 15 mm2 calvarial defects were randomly divided into four treatment groups: control, nPRP, ASC, or nPRP + ASC groups. For treatment, rabbits received a collagen sponge (Gelfoam®) saturated with 1 ml normal saline (controls), 1 ml non-activated PRP (nPRP group), 2 × 106 ASCs (ASCs group), or 2 × 106 ASCs plus l ml nPRP (nPRP + ASCs group). After 16 weeks, bone volume and new bone surface area were measured, using three-dimensional computed tomography and digital photography. Bone regeneration was also histologically analyzed.


Bone surface area in the nPRP group was significantly higher than both the control and ASC groups (p < 0.001 and p < 0.01, respectively). The percentage of regenerated bone surface area in the nPRP + ASC group was also significantly higher than the corresponding ratios in the control group (p < 0.001). The volume of new bone in the nPRP group was increased compared to the controls (p < 0.05).


Our results demonstrate that slow-releasing growth factors from nPRP did not influence ASC activation in this model of bone healing. PRP activation is important for the success of combination therapy using nPRP and ASCs.

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This study was funded by the National Research Foundation of Korea (NRF) funded by the Korean government (No. NRF-2018R1D1A1B07042537).

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Correspondence to In Sik Yun.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Yonsei University Animal Care and Experiment Committee (2013–0408).

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The authors declare that they have no conflict of interest.

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Jeong, W., Kim, Y.S., Roh, T.S. et al. The effect of combination therapy on critical-size bone defects using non-activated platelet-rich plasma and adipose-derived stem cells. Childs Nerv Syst 36, 145–151 (2020).

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  • Mesenchymal stem cells
  • Platelet-rich plasma
  • Osteogenesis
  • Skull