Abstract 

A report of the case of a long-standing aesthetic patient who developed delayed pain following hyaluronic acid filler injection to the nasolabial fold. Despite initial response to standard vascular occlusion management, symptoms recurred, prompting the introduction of adjunctive regenerative therapies including polynucleotides, exosomes, and growth factors. These regenerative modalities, used alongside repeated Hyalase, were selected for their potential to stimulate angiogenesis, modulate inflammation, and support tissue repair. The case highlights both the challenges of managing vascular compromise and the potential role of regenerative adjuncts in optimising recovery and patient satisfaction. 

Case presentation 

A female patient, who had attended regularly for aesthetic treatments over many years, received 0.1ml of hyaluronic acid filler into the left nasolabial fold using a linear thread technique, placed outside the fossae region. 

The fossae (often referring to the pyriform or paranasal fossa) is considered a higher-risk site because of the variable course of the facial artery and its branches, which may run superficially or across the nasolabial fold, creating potential for vascular compromise even with small-volume injections.1-3 Practitioners should therefore remain vigilant when treating this area despite its frequent use in aesthetic practice. 

The procedure itself was uneventful. Immediate post-treatment observations were unremarkable, with no pain beyond normal injection sensation, no blanching, and no bruising. 

Approximately 24 hours later, the patient reported delayed pain radiating up the side of the nose. On review, clinical presentation raised strong suspicion of vascular compromise. Following discussion and signed consent, an initial round of Hyalase was administered. This resulted in a rapid improvement in capillary refill (from 3 to 1 second) and reduction of pain (8/10 to 4/10). 

At 48 hours, pain intensified once more. A second round of Hyalase again improved symptoms. At this stage, adjunctive regenerative treatments were introduced. 

Regenerative treatment approach 

Polynucleotides (Plinest®) 

• Protocol: Daily delivery of 1ml via cannula using a microdroplet intradermal technique for one week, then reduced to every three days, followed by weekly sessions after four weeks. Product was administered evenly throughout the mid and lower face, including the nasolabial folds, to ensure homogenous distribution and stimulation of dermal fibroblasts. 

• Total administered: 14 ml. 

• Rationale: Polynucleotides such as Plinest® have been shown to stimulate fibroblast activity, enhance extracellular matrix remodelling and promote angiogenesis, thereby supporting tissue repair in compromised or injured skin.4-6 Plinest®️ supports reperfusion by encouraging neovascularisation and improving tissue oxygenation. Its regenerative properties help minimise ischemic damage and accelerate recovery of compromised skin. 

Exosomes (Purasomes) 

• Protocol: Applied topically via a 2ml syringe throughout recovery, with 2ml given for use at home in the morning and 2ml for the evening. 

• Total administered: 6 ml. 

• Rationale: Purasomes are exosome-rich vesicles derived from purified bovine colostrum, containing proteins, lipids, and signalling molecules that facilitate intercellular communication. They have been reported to promote angiogenesis, modulate inflammation, and support dermal repair.7,8 Applied topically Purasomes were chosen for their paracrine signalling capacity and role in cellular communication. By delivering exosomal growth factors and proteins directly into the dermis, they aid in reducing inflammation, supporting cellular repair, and improving skin barrier recovery post-ischemic injury. This enhances the regenerative cascade initiated by the polynucleotide injections. 

Cellderma GF5 Growth Factors 

• Protocol: Daily application for one week, reduced to every three days thereafter. 

• Rationale: GF5 is a topical bio-regenerative serum containing five recombinant human growth factors, designed to mimic endogenous signalling proteins that decline with age. These growth factors are reported to stimulate fibroblast and keratinocyte activity, promote extracellular matrix renewal, improve collagen synthesis, accelerate re-epithelialisation and support vascular regeneration.9,10 This step was particularly important for restoring skin integrity and reducing the risk of post-inflammatory changes following vascular insult. 

Supportive measures 

• Daily review by FaceTime or text during the acute phase. 

• Stress management support via Emotional Freedom Techniques (EFT) tapping, a mind-body intervention where patients gently tap on specific acupressure points while focusing on stress or discomfort. EFT has been associated with reductions in anxiety and improved coping in clinical and self-care contexts.13 

• Introduction of a PCA Brightening Peel, a superficial chemical peel containing alpha hydroxy acids (AHA) designed to promote epidermal exfoliation, reduce pigmentation irregularities, and improve early textural changes. PCA Skin peels are widely used in aesthetic practice and have published evidence supporting their safety and efficacy in treating dyschromia and uneven skin texture.14 

• Ongoing medical-grade skincare with Obagi®️ products. Following the acute management phase, I recommended the introduction of an Obagi®️ medical-grade skincare protocol to support long-term skin recovery and optimise treatment outcomes. Obagi®️ products were selected for their evidence-based formulations, clinical efficacy, and ability to address both barrier restoration and pigmentation concerns that may follow vascular events. Key considerations included: 

• Barrier Repair & Hydration:Formulations such as Obagi Hydrate®️ provide sustained moisturisation, protecting against transepidermal water loss and creating an optimal environment for dermal and epidermal healing. 
• Antioxidant Protection:Incorporating Obagi Professional-C®️ serum helps reduce oxidative stress, which is elevated following ischemic insult, thereby minimising free-radical damage and promoting healthier collagen synthesis. 
• Pigmentation Control:The use of Obagi Nu-Derm®️ and related protocols offers targeted solutions for post-inflammatory hyperpigmentation, a common sequela in ischemic skin injuries. 
• Long-Term Skin Health:By integrating medical-grade retinoids at a later stage, cellular turnover and collagen stimulation are enhanced, supporting the regenerative work initiated during the acute management phase. 

Overall, the rationale for Obagi®️’s inclusion was to provide a structured, clinically proven aftercare regimen that would extend beyond crisis management, ensuring the patient achieved both functional recovery and aesthetic optimisation. 

• Maintenance treatments every six to eight weeks with peels, polynucleotides, and exosomes. 

Clinical development 

By days seven to eight, there was marked improvement, with no evidence of necrosis. Skin remained intact and capillary refill consistently measured at one second. At weeks four to six, temporary deterioration occurred due to discontinuation of medical-grade skincare and substitution with over-the-counter products, leading to pustular eruption.  

This was resolved with a targeted AHA peel and resumption of medical skincare. 

At the time of writing, the patient’s skin is not fully back to baseline; however, visible recovery has been substantial. With light makeup, there is no detectable abnormality. The patient reports high satisfaction with both the outcome and the regenerative approach adopted.