Platelet Concentrates for Bone Regeneration: Cellular Composition Decides the Therapeutic Outcome

Abstract

Dear Editor,

We read with great interest the article by Yang et al. (2024)¹ that explores the potential role of platelets in bone regeneration. The authors provide a comprehensive overview of the role of platelets in bone healing, emphasizing their contributions to hematoma formation, inflammatory responses, and angiogenesis. While the article also highlights the therapeutic potential of platelet-rich plasma (PRP) in bone regeneration, we would like to expand on the critical role of cellular composition in platelet concentrates and its influence on therapeutic outcomes that the authors missed.¹

Platelets are a rich source of growth factors, cytokines, and membrane proteins that play a pivotal role in tissue repair. However, the heterogeneity in clinical outcomes observed with PRP therapy can be attributed to the variability in the cellular composition of PRP preparations.² This can become an issue, especially when authors fail to report the composition of the PRP used in their study. Unlike growth factor-based therapies, where the concentration of growth factors can be precisely controlled, PRP releases growth factors in a burst manner upon activation, making it challenging to regulate their release kinetics.³ This uncontrolled release can lead to supraphysiological concentrations of growth factors, which may paradoxically inhibit bone regeneration rather than promote it. One of the key factors contributing to this variability is the presence of leukocytes in PRP (Fig. 1).^4,5 Leukocytes, while contributing to antimicrobial properties, can also release proinflammatory cytokines, which may exacerbate inflammation and impair bone healing.⁵ Studies have shown that leukocyte-rich PRP (LR-PRP) can induce a more pronounced inflammatory response than leukocyte-poor PRP (LP-PRP),⁵ potentially leading to delayed healing or fibrosis. Therefore, the leukocyte content in PRP preparations must be carefully considered when designing therapeutic strategies for bone regeneration.

FIG. 1.

Preparation of PRP with different cellular composition. A line was drawn 5 mm above the buffy coat in separated blood, dividing the upper layer into platelet-poor plasma (PPP) (upper) and PRP (lower). (A) The shaded target layer represents LP-PRP. (B) Aspirating above this layer yields purified PRP with low platelet concentration and no leukocytes. (C) Aspirating below increases platelet concentration but retains leukocytes, forming leukocyte-rich PRP. Reproduced from Kikuchi et al. (2019)⁴ under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). PRP, platelet-rich plasma; LP-PRP, leukocyte-poor platelet-rich plasma.

Another critical aspect is the activation method used to release growth factors from platelets.⁴ The burst release of growth factors following activation can be modulated using different activation agents, such as calcium chloride and thrombin. For instance, slow-release formulations or controlled activation techniques could help mitigate the adverse effects of high initial growth factor concentrations, thereby enhancing the therapeutic efficacy of PRP.

We propose that future research should also focus on standardizing PRP preparation protocols to control cellular composition, particularly leukocyte content, and optimize activation methods to achieve a more controlled release of growth factors. Such standardization could help reconcile the heterogeneity in clinical outcomes and improve the reproducibility of PRP-based therapies.² Therefore, while platelets hold immense potential for promoting bone regeneration, the cellular composition of PRP and the presence of leukocytes play a significant role in determining its biological activity.⁵ By addressing these factors and developing strategies to control the release of growth factors, we can harness the full therapeutic potential of PRP for bone healing. We commend the authors for their insightful review and hope that our comments contribute to the ongoing discourse on optimizing PRP-based therapies for bone regeneration.

Sincerely,

Dr. S. Amitha Banu, MVSc, PhD

Dr. Khan Sharun, MVSc, PhD

Footnotes

Authors’ Contributions

S.A.B.: Concept, writing—original draft, writing—review and editing. K.S.: Supervision, writing—original draft, writing—review and editing.

Data Availability

No data were used for the research described in the article.

Author Disclosure Statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding Information

The authors declare that no funds, grants, or other support were received during the preparation of this article.

References

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