PRP for Hair Growth

Normal Hair Follicle Anatomy and Life Cycle

Normal hair follicles contain a bulb structure on the inferior portion below the shaft (Figure 1). Within the bulb, a follicular matrix surrounds the dermal papilla, the structure that’s perfused by capillaries and small blood vessels that deliver essential nutrients to the follicle[1]. Blood perfusion to the papilla is required for the hair shaft to grow, maintain its thickness and density (Figure 2). The three phases of a hair follicle are summarized[2]:

  1. Anagen Phase: proliferation phase marked by growth of the hair shaft.
  2. Catagen Phase: marked by regression of the bulb and dermal papilla.
  3. Telogen Phase: resting phase marked by separation of the papilla from the follicle shedding of club hairs.

Figure 1: Left is a normal hair follicle with the bulb resting in the epidermis measuring 3-4mm from the dermal papilla to the surface of the skin. Right depicts miniaturization of the hair follicle and loss of perfusion to the papilla, resulting in a much smaller bulb that resides that measures 1-2mm from papilla to the surface.

Figure 2: Depicts the 3 phases of the hair follicle growth cycle – Anagen, Catagen and Telogen. 

Androgenic Alopecia

About one-half of Caucasian men develop androgenetic alopecia (male-pattern baldness) by the time they turn 50 years old[3], while about 40% of postmenopausal woman experience it at the same age[4,5]. American Hair Loss Association reports AGA is responsible for 95% of hair loss in men[6].

AGA is a genetic condition characterized by higher levels of dihydrotestosterone (DHT) and/or changes to the androgen receptor gene. Activation of the androgen receptor shortens anagen phase and moves the follicle into catagen phase. In turn, follicles shrink (miniaturize), and the papilla begins to pull away from connecting capillaries[7,8,9]. This results in thinner and shorter hair follicles that begin to shed off the surface of the scalp.

A lack of blood supply and nutrients prevent follicle nourishment, but regression of the dermal papilla further prevents communication between papillae and their neighboring stem and matrix cells, which is essential to continued health and growth of the hair cell.

How Does PRP Work?

After preparing and administering PRP into the scalp, platelets become activated by collagen and thrombin fragments throughout the soft tissue. Activated platelets then release their granules, which contain numerous growth factors and signaling molecules that stimulate hair growth[10,11,12]. The growth factors and signaling molecules cause a myriad of downstream effects that cause:

  • Follicles to enter Anagen Phase

  • Increases in follicle blood flow via angiogenesis

  • Hair cell proliferation and survival

  • Delayed apoptosis and Catagen Phase entry

More detailed biomolecular mechanisms of how PRP accomplishes these effects can be found below.

PRP Mechanism of Action

Platelet dense- and α-granules contain several growth factors and cytokines beneficial to hair growth. Although many of the cytokines involved in hair restoration are inflammatory cytokines that help remove atherosclerotic plaques and debris stunting growth, the growth factors that bind to dermal papilla cells offer more profound growth potential[10,11,12]. Vascular Endothelial growth factor (VEGF), Epidermal growth factor (EGF) and Platelet-derived growth factor (PDGF) stimulate neovascularization and capillary vessels to grow into the papilla (anagen-associated angiogenesis)[13,14]. PDGF, EGF and VEGF bind to papilla receptors and inhibit glycogen synthase kinase 3-β, promote protein kinase B/AKT signaling, prevent β-catenin degradation, and inhibit Bcl-2-associated apoptosis (Figure 2). In turn, these pathways promote downstream effects on hair follicles:

  • Follicle entry and prolongation of anagen phase
  • Increased blood flow to follicles via angiogenesis
  • Cell proliferation and survival
  • Prevent apoptosis and entry into catagen phase

Figure 3. Growth factors foster survival, proliferation, and differentiation signals in dermal papilla cells. Dickkoft-1 inhibits the canonical wingless (Wnt)/b-catenin pathway leading to an inhibition of the production of cytokines and growth factors that signal differentiation to the epithelial cells as well as prevents vascularization and proliferation. Wnt/b-catenin inhibition is also regulated by glycogen synthase kinase (GSK)-3b, which targets b-catenin for degradation through phosphorylation. Binding of platelet rich plasma growth factors to their respective receptors (GFR) stimulates protein kinase B (Akt) and extracellular regulated kinase signaling which results in cell survival, proliferation and angiogenesis. Akt prevents apoptosis and promotes cytoplasmic b-catenin accumulation through phosphorylative inhibition of Bcl-2-associated death and GSK-3b, respectively. Subsequently, b-catenin enters the nucleus and acts as a coactivator of transcription in combination with members of the T-cell factor/ lymphoid enhancer-binding factor (TCF/LEF) family to induce differential gene expression.

From Gentile, Pietro et al. “Platelet-Rich Plasma and Micrografts Enriched with Autologous Human Follicle Mesenchymal Stem Cells Improve Hair Re-Growth in Androgenetic Alopecia. Biomolecular Pathway Analysis and Clinical Evaluation.” Biomedicines vol. 7,2 27. 8 Apr. 2019, doi:10.3390/biomedicines7020027

Other growth factors nurture and prolong anagen phase by promoting proliferation and survival, decreasing inflammation, preventing early entry to catagen phase and enhancing surrounding muscle and fat cells[10-12]. A more complete list of PRP growth factors and cytokines and their effect on hair can be seen in Table 1 below.

Other Considerations

Exogenous Platelet Activators

Adding platelet activators like calcium chloride or thrombin have shown to activate platelets, but in obstructive ways[14]. Several studies suggest these aggregation inducers may not necessarily result in better hair restoration outcomes as significant change in the concentration of some growth factors does not always occur[15,16]. Moreover, in vivo studies suggest delivery of non-activated PRP enables thromboxane A2 (TXA2) production by platelets, which activate additional platelets and amplify platelet aggregation (Table 2)[17].

Table 2. Differences in hair density between activated and non-activated PRP. The clinical evaluation used calcium gluconate as an exogenous activator prior to PRP injections into the scalp.

Cervelli V, Garcovich S, Bielli A, et al. The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation. BioMed Res Int. 2014; 2014:760709
[16] Singhal P, Agarwal S, Dhot PS, Sayal SK. Efficacy of platelet-rich plasma in treatment of androgenic alopecia. Asian J Transfus Sci. 2015; 9(2):159–162

Frequency & Time Between Procedures

PRP studies on AGA have shown promising improvements in hair density, hair count, hair thickness, and other microscopic evaluations[18-20]. Studies suggest that optimum results for hair are achieved when PRP is performed once a month for 3-4 months and then continuing treatment maintenance every 4-6 months. The most effective platelet solution for hair is a platelet concentrate 4-7 times greater than whole blood levels[13] (See Platelet-rich Plasma: Understanding Mechanisms and Parameters that Determine PRP Efficacy to learn how to best obtain this concentration). In many cases, patients begin noticing results after 60 days of the first injection. It is also important to set expectations: the procedure does not work for everyone. Hair that’s been dormant for a longer period of time does not respond as well. Since AGA is a chronic progressive disorder, it often demands long-term maintenance with PRP for success.

Citations

[1] Buffoli B, Rinaldi F, Labanca M, Sorbellini E, Trink A, Guanziroli E, Rezzani R, Rodella LF. The human hair: from anatomy to physiology. Int J Dermatol. 2014 Mar;53(3):331-41. doi: 10.1111/ijd.12362. Epub 2013 Dec 30. PMID: 24372228.

[2] Martel JL, Miao JH, Badri T. Anatomy, Hair Follicle. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470321/

[3] (1) Ho CH, Sood T, Zito PM. Androgenetic Alopecia. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430924/.

[4] Piraccini, B.M.; Alessandrini, A. Androgenetic alopecia. G Ital. Dermatol. E Venereol. 2014, 149, 15–24.

[5] Shannon, F.; Christa, S.; Lewei, D.; Carolyn, G. Demographics of women with female pattern hair loss and the effectiveness of
spironolactone therapy. J. Am. Acad. Dermatol. 2015, 73, 705–706.

[6] American Hair Loss Association: https://www.americanhairloss.org/men_hair_loss/introduction.html

[7] Gupta AK, Carviel J. A mechanistic model of platelet-rich plasma treatment for androgenetic alopecia. Dermatol Surg. 2016; 42(12):1335–1339

[8] Sawaya ME, Price VH. Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol. 1997; 109(3):296–300

[9] Schweikert HU, Wilson JD. Regulation of human hair growth by steroid hormones. II. Androstenedione metabolism in isolated hairs. J Clin Endocrinol Metab. 1974; 39(6):1012–1019

[10] Gupta AK, Versteeg SG, Rapaport J, Hausauer AK, Shear NH, Piguet V. The Efficacy of Platelet-Rich Plasma in the Field of Hair Restoration and Facial Aesthetics-A Systematic Review and Meta-analysis. J Cutan Med Surg. 2019 Mar/Apr;23(2):185-203. doi: 10.1177/1203475418818073. Epub 2019 Jan 4. PMID: 30606055.

[11] Gentile P, Cole JP, Cole MA, et al. Evaluation of not activated and activated prp in hair loss treatment: role of growth factor and cytokine concentrations obtained by different collection systems. Int J Mol Sci. 2017; 18(2):E408

[12] Gentile P, Scioli MG, Bielli A, et al. Platelet-Rich Plasma and Micrografts Enriched with Autologous Human Follicle Mesenchymal Stem Cells Improve Hair Re-Growth in Androgenetic Alopecia. Biomolecular Pathway Analysis and Clinical Evaluation. Biomedicines. 2019;7(2):27. Published 2019 Apr 8. doi:10.3390/biomedicines7020027

[13] Li ZJ, Choi HI, Choi DK, et al. Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth. Dermatol Surg. 2012; 38(7 Pt 1):1040–1046

[14] Mecklenburg L, Tobin DJ, Müller-Röver S, et al. Active hair growth (anagen) is associated with angiogenesis. J Invest Dermatol. 2000; 114(5):909–916 Hausauer, Amelia K., and Derek Jones. PRP and Microneedling in Aesthetic Medicine. Thieme, 2019.

[15] Cervelli V, Garcovich S, Bielli A, et al. The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation. BioMed Res Int. 2014; 2014:760709

[16] Singhal P, Agarwal S, Dhot PS, Sayal SK. Efficacy of platelet-rich plasma in treatment of androgenic alopecia. Asian J Transfus Sci. 2015; 9(2):159–162

[17] Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994-8. doi: 10.1073/pnas.72.8.2994. PMID: 1059088; PMCID: PMC432905.

[18] Betsi EE, Germain E, Kalbermatten DF, Tremp M, Emmeneg ger V. Platelet-rich plasma injection is effective and safe for the treatment of alopecia. Eur J Plast Surg. 2013; 36(7): 407–412

[19] Gentile P, Garcovich S, Bielli A, Scioli MG, Orlandi A, Cervelli V. The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med. 2015; 4(11):1317–1323

[20] Khatu SS, More YE, Gokhale NR, Chavhan DC, Bendsure N. Platelet-rich plasma in androgenic alopecia: myth or an effective tool. J Cutan Aesthet Surg. 2014; 7(2):107–110