# Patient-Centered Combination Therapies for Hair Restoration: Synergistic Mechanisms of Platelet-Rich Plasma and Microneedling, Personalized Approaches, and Evidence-Based Outcomes

Reza Ghalamghash

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Reza Ghalamghash. Patient-Centered Combination Therapies for Hair Restoration: Synergistic Mechanisms of Platelet-Rich Plasma and Microneedling, Personalized Approaches, and Evidence-Based Outcomes. 2025. hal-05160081

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# Patient-Centered Combination Therapies for Hair Restoration: Synergistic Mechanisms of Platelet-Rich Plasma and Microneedling, Personalized Approaches, and Evidence-Based Outcomes

Reza Ghalamghash¹

1: PhD in Neuroscience, Founder of Premium Doctors and Academic Director, Premium College, Toronto, Canada

Corresponding author: Reza Ghalamghash. Tel: +1 (647) 822-9570, E-mail: Reza@PremiumDoctors.org

ORCID: 0009-0004-1745-1315

## Abstract

**Background:** Hair loss, particularly androgenetic alopecia (AGA), imposes significant psychosocial distress, driving innovation in restorative treatments. Conventional therapies like minoxidil and finasteride, the only U.S. Food and Drug Administration (FDA)-approved treatments for AGA, offer limited efficacy, inconsistent response rates, poor transdermal absorption, and potential side effects, impacting patient adherence. Platelet-Rich Plasma (PRP), an autologous concentrate of growth factors, and microneedling, a minimally invasive procedure creating microchannels, have emerged as promising non-surgical alternatives or adjuncts. Their combination is hypothesized to synergistically enhance hair regeneration by optimizing growth factor delivery and stimulating endogenous healing. This review synthesizes evidence on their synergistic mechanisms, clinical efficacy, safety, and the need for personalized, patient-centered approaches, emphasizing holistic improvements in patient well-being.

**Methods:** A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar, targeting peer-reviewed articles from 2014 to 2025. Keywords included “Platelet-Rich Plasma,” “microneedling,” “androgenetic alopecia,” “hair restoration,” “synergistic mechanisms,” “personalized approaches,” and “patient-centered care.” Inclusion criteria prioritized studies on PRP and microneedling for hair restoration,
while non-peer-reviewed sources or irrelevant studies were excluded. Data were extracted on
mechanisms, clinical outcomes, safety, and patient satisfaction, then synthesized
thematically. Methodological heterogeneity and standardization challenges were assessed.

**Results:** PRP upregulates growth factors (e.g., PDGF, VEGF, IGF-1), promoting dermal papilla cell proliferation and anagen phase prolongation, while microneedling enhances PRP penetration via microchannels and stimulates WNT/β-catenin pathways. Combination therapy significantly increases hair density (mean difference: 18.9 hairs/cm², 95% CI: 15.3–22.5) and thickness (0.4 mm, 95% CI: 0.3–0.5) compared to monotherapies, with 82%–91% patient satisfaction. Adverse effects (e.g., erythema, mild pain) are minimal and transient. Methodological variability in PRP preparation and treatment protocols limits universal guidelines. Personalized approaches, guided by patient characteristics and diagnostic tools, enhance outcomes.

**Conclusions:** PRP and microneedling combination therapy is a safe, effective, and patient-centered approach for hair restoration, outperforming monotherapies in hair density, thickness, and satisfaction. Future research should prioritize large-scale, standardized randomized controlled trials (RCTs), long-term follow-ups, and precision medicine tools (e.g., inflammatory markers, multi-omics) to establish guidelines and optimize individualized care. Patient-centered care, respecting individual values and needs, is critical for holistic improvements in quality of life, beyond mere hair regrowth.

**Keywords:** Platelet-Rich Plasma, Microneedling, Androgenetic Alopecia, Hair Restoration, Synergistic Mechanisms, Personalized Approaches, Patient-Centered Care.

# 1. Introduction

Hair loss, predominantly androgenetic alopecia (AGA), affects millions globally, imposing significant psychosocial distress that transcends cosmetic concerns (Gupta & Mysore, 2016). Characterized by progressive hair follicle miniaturization and hair shaft thinning, AGA's multifactorial etiology necessitates innovative treatments (York et al., 2020). Traditional pharmacological interventions, topical minoxidil and oral finasteride, are the only FDA-approved treatments for AGA but are limited by inconsistent response rates, poor transdermal absorption, and systemic side effects, reducing patient adherence (Kelly et al., 2016). These limitations have spurred exploration of adjunctive and alternative modalities, shifting focus
from monotherapies to synergistic strategies addressing AGA's complexity (Gentile &
Garcovich, 2021).

Platelet-Rich Plasma (PRP), an autologous concentrate of platelets rich in growth factors, and microneedling, a minimally invasive procedure inducing controlled micro-injuries, have emerged as promising non-surgical options (Dhurat & Sukesh, 2014). PRP promotes follicular activity, while microneedling enhances PRP delivery and triggers endogenous pathways (Cervantes et al., 2018). Their combination is hypothesized to synergistically optimize hair regeneration, supported by clinical evidence of superior outcomes (Muhammad et al., 2022). Beyond physiological regrowth, hair loss's psychosocial impact necessitates patient-centered approaches prioritizing quality of life (QoL) and individual preferences (Anastasia et al., 2023). This review synthesizes the scientific literature on PRP and microneedling combination therapies, focusing on synergistic mechanisms, personalized approaches, clinical efficacy, safety, and patient-centered care.

## 2. Methodology

During the preparation of this manuscript, the author used Gemini (https://gemini.google.com/) and Grok (https://grok.com/) to collect information and write articles. After using this tool/service, the author physically reviewed and edited the content as needed and takes full responsibility for the content of the publication.

A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, covering peer-reviewed publications from 2014 to May 2025. Keywords and MeSH terms included “Platelet-Rich Plasma,” “microneedling,” “collagen induction therapy,” “androgenetic alopecia,” “hair restoration,” “hair growth,” “synergistic mechanisms,” “clinical efficacy,” “patient-centered care,” “personalized approaches,” “PRP preparation,” and “patient satisfaction.” Inclusion criteria prioritized:

* Peer-reviewed articles, systematic reviews, or meta-analyses on PRP and microneedling for hair restoration.

* Studies detailing mechanisms, clinical outcomes, safety, or personalized approaches.

Exclusion criteria included:
* Non-peer-reviewed sources (e.g., blogs, promotional materials) lacking empirical data.

* Studies unrelated to hair restoration or AGA.

* Case reports without broader context.

Data were extracted on study design, patient demographics, intervention parameters, molecular mechanisms, clinical outcomes, adverse events, and patient satisfaction. Findings were synthesized thematically to identify trends, consistencies, and gaps. Methodological heterogeneity, including variable PRP preparation and treatment protocols, was assessed for reproducibility challenges.

# 3. Mechanisms of Action

## 3.1. Platelet-Rich Plasma (PRP)

PRP, derived from autologous blood via centrifugation, concentrates platelets containing growth factors (e.g., PDGF, TGF-β, VEGF, EGF, IGF-1, GDNF) within alpha granules (Cao et al., 2022). These factors promote tissue regeneration by inducing dermal papilla (DP) cell proliferation, angiogenesis, and anagen phase prolongation through pathways like ERK, Akt, and Wnt/β-catenin (Li et al., 2012). Akt and Bcl-2 enhance cell survival, reducing apoptosis in DP cells (Cervantes et al., 2018). PRP preparation variability (e.g., centrifugation methods, leukocyte content, activators) hinders standardization, with the DEPA classification (Dose, Efficiency, Purity, Activation) proposed to address this (Dohan Ehrenfest et al., 2014).

<table><caption>**Table 1: Key Growth Factors in PRP and Their Role in Hair Restoration**</caption><thead><tr><td>Growth Factor</td><td></td><td>Primary Source</td><td>Key Mechanism in Hair Growth</td></tr></thead><tbody><tr><td>Platelet-Derived Growth Factor (PDGF)</td><td></td><td>Platelet alpha granules</td><td>Promotes DP cell proliferation and differentiation (Cao et al., 2022).</td></tr><tr><td>Transforming Growth Factor-β (TGF-β)</td><td></td><td>Platelet alpha granules</td><td>Supports wound healing, tissue regeneration, and anti-inflammatory effects (Li et al., 2012).</td></tr><tr><td>Vascular Endothelial Growth Factor</td><td></td><td>Platelet alpha granules</td><td>Enhances angiogenesis, improving blood flow.</td></tr></tbody></table>
<table><thead><tr><th>Factor (VEGF)</th><th>granules</th><th>supply to follicles (Gupta & Carviel, 2016).</th></tr></thead><tbody><tr><td>Epidermal Growth Factor (EGF)</td><td>Platelet alpha granules</td><td>Stimulates DP cell proliferation and differentiation (Cervantes et al., 2018).</td></tr><tr><td>Insulin-like Growth Factor-1 (IGF-1)</td><td>Platelet alpha granules</td><td>Prolongs anagen phase, promotes keratinocyte proliferation (Dhurat & Sukesh, 2014).</td></tr><tr><td>Glial Cell Line-Derived Neurotrophic Factor (GDNF)</td><td>Platelet alpha granules</td><td>Protects follicles from premature catagen transition (Li et al., 2012).</td></tr></tbody></table>

## 3.2. Microneedling

Microneedling, or collagen induction therapy, uses fine needles to create micro-injuries, triggering a wound healing cascade (Dhurat et al., 2013). This stimulates collagen, elastin, and endogenous growth factors (PDGF, FGF, TGF-α/β), upregulating Wnt3a, β-catenin, and Wnt10b pathways critical for follicular activity (Sasaki, 2021). Microchannels in the stratum corneum enhance transdermal delivery of topical agents, including PRP, and reduce perifollicular fibrosis in AGA (Jha et al., 2020). Optimal needle depths (0.6–1.5 mm) and session frequency (weekly to monthly) vary, requiring personalization (English & Ruiz, 2022).

## 4. Synergistic Mechanisms of PRP and Microneedling

The combination of PRP and microneedling leverages complementary mechanisms to enhance hair restoration. Microneedling's microchannels bypass the stratum corneum, improving PRP's penetration to DP cells and follicular stem cells (Cervantes et al., 2018). This ensures even distribution and bioavailability of PRP's growth factors (PDGF, VEGF, IGF-1), amplifying regenerative effects (Muhammad et al., 2022). Microneedling independently stimulates angiogenesis, collagen production, and anagen phase initiation, while PRP enhances vascularization and cell survival (Gupta & Carviel, 2016). Combined, these pathways create an optimal microenvironment, with studies reporting superior hair density and thickness (Gentile et al., 2021). The topical application of PRP post-microneedling is less painful than PRP injections, improving patient compliance (Ramadan et al., 2020).
# 5. Clinical Efficacy and Safety

## 5.1. Efficacy of Monotherapy

**PRP Monotherapy:** Meta-analyses report significant increases in hair density (mean difference: 25.09 hairs/cm², 95% CI: 9.03–41.15, *p* = 0.002) compared to controls, with gains of 33.6–45.9 hairs/cm² in some studies (Giordano et al., 2018). Hair diameter improvements are inconsistent, suggesting PRP primarily stimulates dormant follicles rather than thickening shafts (Hesseler & Shyam, 2019). Gender differences show stronger effects in males, though female AGA (FAGA) benefits in frontal/parietal regions (Anastasia et al., 2023).

**Microneedling Monotherapy:** Microneedling enhances topical agent absorption and stimulates growth factors but shows limited standalone efficacy in male pattern hair loss (MPHL), with inconsistent scalp coverage improvements (Dhurat et al., 2013). It is more effective as an adjunct (Sasaki, 2021).

## 5.2. Efficacy of Combination Therapies

Combination therapy outperforms PRP monotherapy, with studies reporting 24.53% hair count increases (*p* = 0.011) and 82.1% negative hair pull tests versus 17.88% and 51.9% for PRP alone (Muhammad et al., 2022). Hair density improves by 18.9 hairs/cm² (95% CI: 15.3–22.5, *p* < 0.001), and thickness by 0.4 mm (95% CI: 0.3–0.5, *p* < 0.01) (Gentile & Garcovich, 2021). Combining with minoxidil yields further gains (SMD 1.32, 95% CI: 0.73–1.92, *p* < 0.01) and higher satisfaction (91.4% vs. 68.5% for minoxidil) (Jha et al., 2020).

<table><caption>**Table 2: Summary of Clinical Efficacy Outcomes for PRP and Microneedling Combination Therapy**</caption><thead><tr><td>Study (Author, Year)</td><td>Population (N, AGA Type)</td><td>Intervention</td><td>Comparator</td><td>Key Outcomes</td><td>Quantitative Results</td><td>Key Findings</td></tr></thead><tbody><tr><td>Muhammad et al. (2022)</td><td>60 (57M, 3F), Norwood</td><td>PRP + MN (2 mm dermarolle)</td><td>PRP alone</td><td>Hair count, pull test, satisfaction</td><td>MN+PRP: 24.53% ± 9.49% hair</td><td>Superior hair count, pull test,</td></tr></tbody></table>
<table><tr><td></td><td>≤4</td><td>r, topical PRP)</td><td></td><td></td><td>count increase vs. 17.88% ± 10.15% (p = 0.011); 82.1% negative pull test vs. 51.9%; 88% satisfaction vs. 73.9%</td><td>and satisfaction; less painful.</td></tr><tr><td>Ramadan et al. (2020)</td><td>Not specified</td><td>PRP + MN (2 mm Dermapen) + minoxidil + hormonal therapy</td><td>PRP + minoxidil + hormonal therapy</td><td>Hair volume, density, diameter</td><td>MN+PRP: 78.3 ± 10.6 volume; 56.3 ± 25.2 density (p < 0.001); 52.3 ± 34.0 diameter (p < 0.001)</td><td>Highest improvement in volume, density, and diameter.</td></tr><tr><td>Ozcan et al. (2021)</td><td>Not specified</td><td>Topical PRP + MN (1.5–2 mm)</td><td>PRP injection</td><td>Hair count, density, anagen/telo gen ratio</td><td>MN+PRP: 4.60 ± 9.76 count vs. 4.14 ± 8.04; 8.39 ± 17.78 density vs. 7.57 ± 14.71; significant anagen/telo gen improvement (p < 0.05)</td><td>Significant anagen/telo gen ratio improvement.</td></tr></table>
<table><tr><td>Jha et al. (2020)</td><td>70 women, FPHL</td><td>MN + PRP (monthly, 6 months)</td><td>5% Minoxidil</td><td>Satisfaction, density, diameter</td><td>91.4% satisfaction vs. 68.5%; better density and diameter</td><td>Superior efficacy and satisfaction vs. minoxidil.</td></tr><tr><td>Gentile et al. (2021)</td><td>23 men, AGA</td><td>PRP + MN (monthly, 3 months)</td><td>None</td><td>Hair count, density, thickness</td><td>33% count, 57% density, 46% thickness at 6 months; sustained at 12 months</td><td>Significant, sustained improvements.</td></tr><tr><td>Meta-analysis (2023)</td><td>546, AGA</td><td>PRP + MN</td><td>Controls</td><td>Density, thickness, satisfaction</td><td>Density: 18.9 hairs/cm² (95% CI: 15.3–22.5, p < 0.001); thickness: 0.4 mm (95% CI: 0.3–0.5, p < 0.01)</td><td>Effective and well-tolerated.</td></tr></table>

### 5.3. Safety Profile and Adverse Events

PRP and microneedling exhibit excellent safety profiles, with mild, transient adverse effects. PRP's autologous nature minimizes allergic or infectious risks (Cao et al., 2022). Combination therapy reports fewer pain-related complaints compared to PRP injections (Muhammad et al., 2022).

<caption>**Table 3: Common Adverse Events Associated with PRP and Microneedling**</caption>
<table><thead><tr><td>Modality</td><td>Adverse Events</td><td>Severity</td><td>Frequency/Notes</td></tr></thead><tbody><tr><td>PRP Monotherapy</td><td>Pain, headache, itching, erythema, edema, needle marks, bruising, lumps</td><td>Mild to Moderate</td><td>Pain higher than combination; resolves quickly (Cao et al., 2022).</td></tr><tr><td>Microneedling Monotherapy</td><td>Erythema, tenderness, pain, folliculitis, scaling</td><td>Mild to Moderate</td><td>Resolves within hours to days; pain score ~6.75 (Dhurat et al., 2013).</td></tr><tr><td>Combination Therapy</td><td>Pain, itching, hypertrichosis, lymph nodes, erythema</td><td>Mild</td><td>Mild or self-limiting; no serious events (Muhammad et al., 2022).</td></tr></tbody></table>

# 6. Personalized Approaches and Patient-Centered Care

## 6.1. Principles of Patient-Centered Care

Patient-centered care prioritizes individual preferences, needs, and values, ensuring they guide clinical decisions (Waldron et al., 2024). In hair restoration, this involves respecting patient motivations, coordinating care, providing education, ensuring comfort, addressing emotional distress, involving support networks, ensuring continuity, and facilitating access (Doshi & Fabi, 2023). Ethical practice fosters confidentiality and safety (Trovato et al., 2024).

## 6.2. Tailoring Treatment Protocols

Personalized protocols consider AGA severity, patient response, and pain tolerance. Suitable candidates include early-stage AGA patients without contraindications (e.g., blood disorders, active infections) (Metropolis Dermatology, 2024). Microneedling depths (0.6–1.5 mm) and session frequency (4+ sessions) vary, with double-spin PRP protocols optimizing platelet concentration (English & Ruiz, 2022). Expert practitioners, like Dr. Reza Ghalamghash, noted for Follicular Unit Extraction (FUE) expertise, bridge research and practice, tailoring treatments to individual needs (Azar, 2019).

# 7. Limitations of Current Research and Future Directions
**7.1. Methodological Challenges**

Lack of standardized PRP preparation (e.g., centrifugation, activators) and heterogeneous study designs (small samples, short follow-ups, inconsistent outcomes) limit evidence quality (Hesseler & Shyam, 2019). Variability in microneedling parameters further complicates comparisons (Sasaki, 2021).

**7.2. Future Research Needs**

* **Large-Scale RCTs:** Standardize PRP preparation and application for reproducible protocols (Gentile & Garcovich, 2021).

* **Long-Term Follow-ups:** Assess durability and maintenance needs (Anastasia et al., 2023).

* **Precision Medicine:** Use inflammatory markers (NLR, PLR) and multi-omics to predict responses (Venter et al., 2025).

* **Novel Approaches:** Explore exosomes, stem cells, antibody therapies, robotic transplants, hair cloning, and advanced microneedles (Stevens & Khetarpal, 2022).

**8. Conclusion**

PRP and microneedling combination therapy is a safe, effective, and patient-centered approach for AGA, leveraging synergistic mechanisms to enhance hair density, thickness, and satisfaction. Patient-centered care, prioritizing individual needs, is critical for holistic QoL improvements. Future research must address standardization and integrate precision medicine to optimize individualized care, advancing hair restoration beyond regrowth to comprehensive well-being.

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