What are known effective skin biostimulators?

Known Effective Skin Biostimulators

The most effective and well-studied skin biostimulators are autologous platelet concentrates (PRP and PRF), poly-L-lactic acid (PLLA), calcium hydroxylapatite (CaHA), polydioxanone (PDO), and hyaluronic acid (HA), with PRF demonstrating superior collagen synthesis compared to PRP in head-to-head studies. 1

Autologous Platelet Concentrates (APCs)

Platelet-Rich Plasma (PRP)

• PRP contains concentrated platelets and growth factors that stimulate tissue repair by promoting angiogenesis, cell migration, proliferation, and collagen deposition 2
• Histopathological studies demonstrate increased dermal thickness, neocollagenosis, enhanced collagen organization, and increased fibroblast activity 1, 2
• PRP stimulates cell proliferation and expression of type I collagen in human dermal fibroblasts 1, 2
• Most effective when administered via intradermal injections spaced 1 cm apart using 27-30 gauge needles 1, 3
• Treatment protocols typically involve 3-6 sessions with 2-3 week intervals between treatments 2
• Effects are visible within 1-3 months but diminish over time, with improvements of 12%, 11%, and 6% at 1,3, and 6 months respectively 2

Platelet-Rich Fibrin (PRF)

• PRF demonstrates over 2-fold improvement in collagen synthesis compared to PRP in vitro 1
• PRF shows superior patient-reported outcomes with 5-fold higher "excellent" ratings compared to PRP for scar treatment 1
• PRF resulted in significant lip rejuvenation at 3 months with well-tolerated minor adverse effects 1
• Must be used within 20-40 minutes after preparation before clotting occurs 3

Albumin-Based APCs (BioFiller)

• Novel development creating an "albumin gel" by heating plasma that lasts 4-6 months when injected while simultaneously building collagen over time 1
• Addresses the primary limitation of liquid APCs which only last a few months 1

Synthetic Biostimulators

Poly-L-Lactic Acid (PLLA)

• PLLA induces controlled foreign body reaction leading to neocollagenesis 4
• Produces type I collagen preferentially in treated tissues 5
• Can be combined with HA, CaHA, and neurotoxins for enhanced facial rejuvenation outcomes 6
• Poly-D,L-lactic acid formulations (AestheFill) are versatile for both facial and body skin rejuvenation 7

Calcium Hydroxylapatite (CaHA)

• CaHA demonstrates biostimulatory effects through controlled foreign body reaction 4
• Can be diluted (1:1 for face, 1:4 for neck) for hyperdilute injection techniques 8
• When combined with topical exosomes, CaHA yields enhanced skin quality faster than either treatment alone 8
• Effective for large surface area treatments when combined with other modalities 6

Polydioxanone (PDO)

• PDO biostimulators show better performance in collagen production compared to PLLA in animal models 5
• Produces more organized hypodermal and dermal tissue thickness 5
• Higher tendency for type III collagen production compared to control tissues 5

Hyaluronic Acid (HA)

• While primarily known as a filler, HA demonstrates biostimulatory effects on tissue 4
• Combining PRP with HA (50:50 mix) provides superior benefit for facial rejuvenation with highly significant improvement in facial appearance and skin elasticity compared to PRP or HA alone (p<0.0001) 1
• Participants treated with PRP-HA cellular matrix showed 20%, 24%, and 17% increase in FACE-Q scores at 1,3, and 6 months post-treatment respectively 1

Combination Approaches

Nanofat with APCs

• Large RCT (103 patients) comparing nanofat with intradermal liquid-PRF injection versus HA injection showed significant skin quality enhancement at 1 month (p<0.01) 1
• Scores at 12 months remained significant in the nanofat-PRF group but not in the HA control group 1

Microneedling with APCs

• Microneedling combined with PRP demonstrates better skin structural improvements than microneedling alone or with TCA 1
• Creates microchannels 0.25-2.5mm deep that facilitate APC delivery directly to dermal fibroblasts 1, 3
• Downtime is typically 24-48 hours, much shorter than comparable methods 1

Cross-Linking Agents with APCs

• Adding cross-linking agents to APCs significantly enhances degradation properties, extending duration from months to 6-18 months similar to commercial HA fillers 1
• Offers advantages of being more natural, markedly cheaper, and presenting better biocompatibility/safety with reduced risk of allergic reactions and vascular occlusions 1

Critical Preparation Considerations

• Trisodium citrate is the most widely used anticoagulant for PRP preparation with few negative effects 9
• EDTA should never be used for PRP preparation as it causes platelet swelling and activation 9
• Platelet concentration, yield, and recovery depend on centrifugation protocol and collection methods 9

Common Pitfalls to Avoid

• Injecting deeper than 2.5mm risks vascular complications and reduces efficacy by missing target dermal fibroblasts 3
• Failing to create visible papules with blanching suggests incorrect depth placement 3
• Using PRF beyond 20-40 minutes after preparation as it will clot in the syringe 3
• Lack of standardization in preparation techniques, dosing protocols, and outcome measurements makes comparison between studies difficult 9, 2