The research team, led by Katerina Green and Deanna Menapace of the Department of Otolaryngology-Head and Neck Surgery, together with colleagues from dermatology and the Mayo Clinic Alix School of Medicine, conducted a systematic PubMed search that identified 19 published studies documenting adverse events associated with regenerative therapeutics in facial plastic surgery. They supplemented this literature analysis with a retrospective chart review of six patients treated at their own institution who experienced complications from these procedures. Their findings paint a detailed picture of what can go wrong when biologically active materials are injected into the highly vascular landscape of the face.

The technical appeal of these therapies is easy to understand. Platelet-rich plasma, or PRP, is derived from a patient’s own blood, which is centrifuged to concentrate platelets and the growth factors they carry. When injected into the skin or scalp, these factors stimulate angiogenesis and collagen synthesis, promoting tissue repair and regeneration. Nanofat, meanwhile, is produced by mechanically emulsifying harvested fat until mature adipocytes are broken down, leaving behind the stromal vascular fraction and adipose-derived stem cells with regenerative properties. Exosomes, tiny extracellular vesicles packed with signaling molecules, represent the newest frontier, marketed for anti-inflammatory and collagen-stimulating effects on skin texture and pore size.

Yet the review reveals that the most devastating complications share a common mechanism: vascular embolism. When injectable material enters an artery, it can travel retrograde into the ophthalmic artery and its branches, occluding blood supply to the retina or brain. The literature documents eight cases of vision loss following PRP injection, six of them permanent. Seven of these occurred after injections into the glabella, the region between the eyebrows where the supratrochlear and supraorbital arteries lie in close proximity to the ophthalmic system. Patients reported losing vision almost immediately, and central retinal artery occlusion is treatable only within an approximately four-hour window, a deadline frequently missed when injections occur in non-hospital settings.

Autologous fat grafting carries even greater documented risk. A systematic review cited in the paper identified 61 cases of arterial embolism after facial fat injection, including six deaths. In one reported case, an 18-year-old woman developed hemiplegia and loss of consciousness 24 hours after temporal fat injection; imaging revealed an infarction of the right external carotid artery caused by fat embolism, and despite decompressive craniotomy she died of central respiratory failure. In another, fat injected into the nasolabial fold entered the dorsal nasal artery and migrated to the ophthalmic artery, causing irreversible blindness. By contrast, nanofat injections appear far gentler: a review of 36 patients treated for periorbital dark circles found only transient bruising and mild edema, both resolving within days.

The Mayo Clinic cases add valuable new detail to this risk map. The first describes a 47-year-old woman who developed painful reactive lymphadenopathy the night after scalp PRP injections for hair loss, requiring emergency evaluation, CT imaging, and antibiotics before symptoms resolved. The authors suggest this may establish PRP alone, independent of microneedling with which it has previously been combined, as a trigger for lymph node swelling, possibly through local trauma or reaction to concentrated growth factors. The second case is the first of its kind: a 51-year-old woman developed facial tingling, numbness, and arm heaviness minutes after scalp PRP, prompting a full stroke workup. When imaging excluded ischemia, clinicians concluded she had experienced an acephalgic migraine with aura triggered by the procedure, a side effect never previously associated with PRP that may be relevant when injections follow trigeminal nerve distributions.

Three further institutional cases involved fat and nanofat. One patient who received temporal microfat and nanofat mixed with PRP developed delayed fat necrosis seven months after surgery, with a fluid collection that required serial aspiration and MRI confirmation, ultimately leaving the aesthetic result suboptimal. Two other patients developed nodular swelling after periorbital nanofat grafting; in one, intralesional triamcinolone resolved the nodules, while in the other persistent fullness required surgical excision, illustrating that treatment responses vary and clinical flexibility is essential. A sixth patient, treated with a topical human-derived exosome product after laser resurfacing, developed facial swelling and blistering consistent with suspected contact dermatitis, believed to be the first reported complication of topical exosome therapy in the United States.

The exosome literature emerging internationally is more concerning. Injectable exosome products are not approved by the US Food and Drug Administration, and their composition varies enormously between manufacturers depending on source material, isolation methods, and processing. Reported complications include granuloma formation, hypersensitivity reactions, persistent nodular lesions refractory to corticosteroids, and painful cutaneous necrosis that responded poorly even to carbon dioxide laser treatment. Notably, many of the severe reactions occurred after injections administered at private, non-hospital clinics, whereas a hospital-based retrospective series of 40 patients receiving exosome skin boosters with microneedling reported only expected erythema and edema resolving within 48 hours.

The authors emphasize that an underappreciated contributor to these complications is the profound heterogeneity of the products themselves. PRP preparation protocols differ in centrifugation speed, duration, and technique, producing wide variation in platelet concentration and cellular composition. Nanofat quality depends on harvesting location, instrumentation, and the number of emulsification passes. Exosome formulations differ in origin and purity. This variability limits reproducibility across studies and clinics, complicates comparisons of safety data, and means that two patients receiving nominally identical treatments may receive biologically distinct products. Regulatory frameworks have struggled to keep pace: the FDA regulates only minimally manipulated, homologous-use human cell products under 21 CFR 1271, PRP largely escapes the HCT/P framework as an autologous blood product, and recent state legislation such as a 2025 Florida law has expanded physician discretion to offer certain non-FDA-approved regenerative therapies.

Prevention, the authors argue, remains the most effective strategy because treatments for established embolic complications are notoriously unreliable. Ocular massage, anterior chamber paracentesis, intraocular pressure-lowering agents, hyaluronidase, hyperbaric oxygen, and intra-arterial thrombolysis have all been attempted for injection-related blindness, and none has proven consistently effective. Recommended safeguards include mapping vascular anatomy before procedures, avoiding bolus injections and previously traumatized sites, using small cannulas with low injection pressure and volume, employing ultrasound guidance where available, and maintaining an emergency protocol for immediate injection cessation with rapid referral to ophthalmology or emergency services. The researchers also call for candid discussion of risks in the literature, noting that favorable safety profiles and underreporting have combined to leave patients and providers underinformed. Their central message is measured rather than alarmist: PRP, fat grafting, and exosome therapies offer real aesthetic benefit when used with stewardship, but providers must understand each modality’s mechanism, screen patients for cardiovascular, hematological, and immunological risk factors, and prepare for the rare but catastrophic complications that these otherwise promising biologics can produce.

Subject of Research: Complications of regenerative medicine therapies, including platelet-rich plasma, fat and nanofat grafting, and exosomes, in facial plastic surgery

Article Title: Complications of regenerative therapeutics in facial plastic surgery: a case series and review of the literature

Article References: Green, K., Pascal, G. J., Tolaymat, L., Bruce, A., & Menapace, D. (2026). Complications of regenerative therapeutics in facial plastic surgery: a case series and review of the literature. BMC Plastic and Reconstructive Surgery, 2(1), Article 19. https://doi.org/10.1186/s44452-026-00032-w

Image Credits: AI Generated

DOI: 10.1186/s44452-026-00032-w

Keywords: regenerative medicine, facial plastic surgery, platelet-rich plasma, fat grafting, nanofat, exosomes, blindness, embolism, aesthetic medicine, complications, PRP, cosmetic injections