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Evidence-based medicine - Orthopaedics - Aesthetic medicine - Sports medicine
Photoactivated PRP (PA-PRP): mechanisms, evidence and practical aspects
A scientific overview of photobiomodulation, release kinetics and published studies
Abstract
In some protocols, PRP is treated with light of defined parameters after preparation. Differences in release kinetics have been described in vitro compared to chemical activation methods. Whether and to what extent these differences have a clinical effect is currently unclear due to the limited and heterogeneous study situation. Small clinical studies have reported indications of differences in individual endpoints (e.g. gonarthrosis, melasma); methodologically robust conclusions cannot be derived from this. In addition to activation protocols, the standardization of preparation and the selection of suitable PRP tubes are also relevant for practical classification. This article summarizes the current status of the mechanism, preparation aspects and published data.
Key Takeaways
- In some protocols, PRP is treated after preparation using light with defined parameters.
- In vitro, differences in release kinetics compared to chemical activation methods have been described; the clinical relevance of these differences has not yet been conclusively clarified.
- Small clinical studies report indications of possible differences in individual endpoints; reliable conclusions are only possible to a limited extent due to limited case numbers and heterogeneous protocols.
- The comparability of published data depends largely on standardized processing protocols - uniform, generally binding standards have not yet been established.
- For other fields of application (tendinopathies, neuroregeneration, chronic wounds), preclinical or methodologically heterogeneous data is available to date.
01Biological mechanism of action
1.1 Photobiomodulation and intracellular signaling cascade
When processed PRP is exposed to polychromatic light sources with defined emission ranges, platelet chromophores - including cytochrome c oxidase in the mitochondrial respiratory chain - absorb the photon energy. Polychromatic light sources with defined emission ranges have been described in published protocols. This initiates a cascade of intracellular events:
- Increased mitochondrial ATP synthesis
- Increased intracellular Ca²⁺ release from the dense tubular system
- Structural activation markers: lamellipodia expansion, pilopodia formation, platelet agglomeration
These activation markers are morphologically comparable with conventionally activated platelets. In vitro, differences in release kinetics compared to chemical activation methods have been described. A direct transfer to clinical conditions is only possible to a limited extent.
1.2 Growth factors described in PRP and their discussed biological functions
| Growth factor | Main source | Discussed biological function |
|---|---|---|
| PDGF (AA, AB, BB) | α-Granules | Proliferation of fibroblasts and smooth muscle cells; recruitment of tissue progenitor cells |
| TGF-β1/β2 | α-Granules | Collagen synthesis, scar remodeling; immune modulation through inhibition of pro-inflammatory cytokines |
| VEGF | α-Granules | Angiogenesis; crucial for vascularization of avascular structures (tendons, menisci) |
| EGF | α-Granules | Epithelial proliferation and migration; relevant for wound closure and dermal regeneration |
| IGF-1 | α-Granules / Plasma | Myoblast proliferation; muscular regeneration after injury |
| HGF | α-Granules | Anti-apoptotic; promotes muscle cell regeneration |
Table 1: Growth factors described in PRP and their discussed biological functions (simplified). Concentrations vary depending on the preparation protocol and individual baseline values.
1.3 Leukocyte status: LR-PRP vs. LP-PRP
The leukocyte content of the preparation is a methodologically relevant parameter, the significance of which is discussed depending on the indication and target tissue:
- LR-PRP (leukocyte-rich): May be associated with a different cell and cytokine profile and more pronounced proinflammatory signals.
- LP-PRP (leukocyte-poor): Discussed in certain settings when a lower concomitant inflammatory profile is desired.
The clinical relevance depends on the indication, preparation, target tissue and endpoint.
Note on the data situation: There are currently no sufficient head-to-head comparisons between LR and LP preparation for PA-PRP. The available studies used specific commercial systems; transferability to other protocols is limited.
02Standardization of reprocessing: What role do PRP tubes play?
The reproducibility of PA-PRP preparation depends on several pre-analytical and procedural parameters. Relevant variables at a glance:
| Parameters | Protocol features described in the literature | Significance for reprocessing |
|---|---|---|
| Blood sample volume | 15-60 ml (depending on indication, varying in published studies) | Larger volumes may be associated with a higher platelet yield; the evaluation remains system- and protocol-dependent |
| Centrifugation | Two-stage centrifugation frequently described in published protocols (soft spin + hard spin) | Separation of erythrocytes and possibly leukocytes; exact g-values depend on the system |
| Platelet concentration | System-dependent; no generally binding threshold values established | Target concentration varies depending on system, indication and protocol |
| Photoactivation | Described in published protocols; system-specific | Concrete parameters (wavelength, irradiation time, distance) have not yet been uniformly standardized |
| Anticoagulant | ACD-A or citrate described in published protocols | EDTA is not usually used in PRP preparation protocols |
| Time of application | Prompt application after activation described in published protocols | Storage of activated preparations not provided for in published studies |
Table 2: Practically relevant preparation parameters for PA-PRP. Device-specific validations are required.
The importance of PRP tubes for standardization: PRP tubes are a relevant component of pre-analytical standardization, as the material, filling volume, anticoagulant, separating gel system and geometric properties can influence the cell profile and the reproducibility of the preparation. Therefore, not only the PRP procedure itself but also the tube system used must be taken into account when evaluating published data.
There is currently no binding European standardization of PRP production (including PA-PRP). Consensus recommendations from the ISBT and various professional associations are available, but do not have any binding regulatory force.
03Evidence situation: published study data at a glance
Individual small studies and a systematic review describe indications of differences compared to standard protocols or comparison groups for certain endpoints. The overall significance remains limited due to limited case numbers, heterogeneous protocols, partly missing control arms and inconsistent endpoints.
3.1 Gonarthrosis
Paterson et al (2016) compared intra-articularly injected PA-PRP with hyaluronic acid in a double-blind, randomized pilot study (n = 37). Differences were reported for individual pain and function scores in the PA-PRP group. The significance and transferability are considerably limited by the small number of cases, the specific commercial system and the short follow-up.
In a prospective cohort study (n = 232, 12 months), Mohiuddin et al. (2018) reported changes in the WOMAC score over the observation period. The lack of a control arm fundamentally limits the interpretability of the results.
A systematic review and a meta-analysis (Simental-Mendía et al., 2023; n = 1,292, 14 studies) examined activated versus non-activated PRP in general - a PA-PRP-specific subgroup analysis is not included. A direct extrapolation to PA-PRP is not methodologically permissible.
3.2 Dermatology: Melasma
Demir and Altun (2024) compared PA-PRP with conventional PRP in a randomized double-blind study (n = 38). Both groups showed changes in the MASI score; a statistically significant group difference was not demonstrated. The number of cases is not sufficient for reliable conclusions.
3.3 In vitro data on release kinetics
A laboratory study (Eur. J. Pharm. Biopharm., 2020) described differences in growth factor release under in vitro conditions over an observation period of 28 days after photoactivation. In vitro data are not directly transferable to in vivo conditions; tissue perfusion, enzymatic environment and binding proteins significantly modify the effective drug distribution.
3.4 Further indication fields
PRP data from heterogeneous studies are available for tendinopathies, androgenetic alopecia and chronic wounds; PA-PRP-specific controlled studies are largely lacking in these indications. Only preclinical data has been published in the field of neuroregeneration.
04Frequently asked questions about the classification of PA-PRP
Photoactivated PRP (PA-PRP) is a procedure in which platelet-rich plasma is exposed to light of defined parameters after preparation. This is a variant of PRP preparation; the methodological and clinical differences to other activation procedures are the subject of ongoing research.
In chemical activation, exogenous substances (e.g. CaCl₂ or bovine thrombin) are added to the prepared PRP. In photoactivation, this addition is omitted; instead, the preparation is exposed to light of certain parameters. Differences in release kinetics have been described in vitro. Whether these differences are clinically relevant cannot be conclusively assessed on the basis of the available studies.
The published data on PA-PRP is heterogeneous and methodologically limited. Existing studies mostly have small numbers of cases, use different protocols and sometimes lack a control arm. Reliable, indication-related conclusions cannot be derived from this. Larger, standardized RCTs are pending.
PRP tubes can influence the composition of the obtained preparation - for example through the anticoagulant, separating gel system, filling volume and process compatibility. For the comparability of protocols and the evaluation of published data, these parameters should be documented and systematically taken into account.
Different centrifugation protocols, tube systems, leukocyte contents and light parameters lead to preparations that are difficult to compare. As published studies often use different systems, the transferability of results is limited. Standardized protocols are a prerequisite for reliable statements on efficacy.
Key open questions include: the clinical relevance of in vitro described release differences; optimal light parameters and their standardization; indication-related efficacy in controlled studies with sufficient numbers of cases; long-term safety; and the transferability of results across different treatment systems.
05Classification of the data situation and need for research
Despite preclinical and mechanistic data, the available evidence on PA-PRP is limited for methodological reasons:
- Small samples: The largest PA-PRP-specific study to date (Mohiuddin et al., n=232) lacks a randomized control arm.
- Lack of standardization: Different preparation systems, leukocyte contents and light sources make comparability difficult.
- Short follow-up periods: Long-term safety data (>12 months) are largely lacking.
- Publication bias: Positive results are preferentially published; negative studies are underrepresented in the PRP literature.
For future research, large-scale, multi-centre RCTs with standardized treatment protocols, validated endpoints and long-term follow-up are required in order to be able to evaluate indication-related statements in a methodologically more robust manner.
Scientific references
- Paterson KL et al. Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: a double-blind, randomized controlled pilot study. BMC Musculoskelet Disord. 2016;17:67.
- Mohiuddin AKM et al. Clinical outcome of photoactivated platelet-rich plasma in the treatment of knee osteoarthritis. Regen Med Ther. 2018;4(1):2-4.
- Simental-Mendía M et al. Comparison of the clinical effectiveness of activated and non-activated platelet-rich plasma in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Clin Rheumatol. 2023;42(3):681-690.
- Demir FT, Altun E. Comparison of platelet-rich plasma efficacy with and without photoactivation in melasma: a randomized double-blind study. J Cosmet Dermatol. 2024. doi:10.1111/jocd.16540
- Sustained release of growth factors from photoactivated PRP. Eur J Pharm Biopharm. 2020;148:67-76.
- Cavallo C et al. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules. Biomed Res Int. 2016;2016:6591717.
- Photo-activated platelet-rich plasma based patient-specific bio-ink for cartilage tissue engineering. Biomed Mater. 2020;15(6).
Technical note This article scientifically classifies published data on photoactivated PRP. It is written for physicians and healthcare professionals. The presentation is intended to provide a professional classification of the published study situation and does not permit any general statements on clinical superiority or specific treatment results.