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

The clinical logic behind platelet-rich plasma, commonly abbreviated PRP, is deceptively simple. Platelets are the blood’s first responders, streaming to sites of injury and releasing a cocktail of growth factors and signaling proteins that orchestrate clotting, inflammation resolution, and tissue rebuilding. By concentrating platelets from a patient’s blood and re-delivering them to a damaged site, clinicians aim to amplify the body’s own repair mechanisms. Because the material is autologous, derived from the patient, it sidesteps immune rejection and disease transmission concerns that complicate donor-derived products. But aging is known to blunt tissue regeneration, raising an uncomfortable question: if regeneration slows with age, does the PRP made from an 80-year-old’s blood still carry the molecular machinery needed to heal?

That is precisely the question addressed by Anna Buisan-Farré, Montserrat Serra-Mas, Marta Otero-Viñas, and colleagues working across the University of Vic – Central University of Catalonia, the Institute for Research and Innovation in Life and Health Sciences in Central Catalonia, and the Institute for Research in Biomedicine in Barcelona. Their study stands out for its focus. Most proteomic investigations of PRP have examined samples from young or mixed-age donors, leaving a substantial evidence gap for the elderly, whose tissues are the ones most in need of regenerative support and whose blood may differ immunologically, hormonally, and in its clotting behavior.

The technical pipeline behind the study reflects the rigor required to make such claims defensible. Blood samples were collected from 32 elderly donors under institutional review board approval with informed written consent. Platelet-rich plasma was prepared by sequential centrifugation, the standard method of separating blood components by density. To release the platelet payload, the researchers activated the platelets with calcium gluconate and heparin, then centrifuged the samples again to strip out residual platelets, leaving behind the soluble protein cargo that a clinician would actually inject. Control plasma samples were processed in parallel to distinguish proteins genuinely concentrated by platelets from those simply circulating in blood.

Mass spectrometry formed the analytical core of the work. Because the most abundant blood proteins, chiefly albumin and immunoglobulins, can mask the rarer signaling molecules of interest, the team first depleted these high-abundance proteins. The remaining proteome was enzymatically digested into peptides and analyzed by liquid chromatography coupled to tandem mass spectrometry, a technique that separates peptides by chemical properties before fragmenting them in the mass spectrometer to infer their amino acid sequences. Bioinformatic pipelines then mapped the identified proteins onto known biological processes using tools such as Gene Ontology biological process annotations and the Kyoto Encyclopedia of Genes and Genomes pathway database.

The headline result is striking: 324 of the 1,378 detected proteins appeared exclusively in the platelet-rich plasma and not in control plasma. Functional analysis showed that the PRP proteome, whether unique to PRP or shared with plasma, was strongly linked to vesicle transport, immune and coagulation processes, cytoskeleton organization, and wound healing. In other words, the concentration step does not merely add platelet fragments; it enriches a coherent biological program centered on the very processes tissue repair demands. Cytoskeleton organization proteins point to cell migration and structural remodeling, while vesicle transport proteins reflect the exosome-rich cargo platelets deliver to injured tissue.

Perhaps the most clinically consequential finding, however, concerns variability. The researchers observed marked inter-individual differences in which proteins were detected across the 32 donor samples, and critically, the proteins showing this person-to-person variability were themselves linked to tissue regeneration processes. That observation carries a double meaning. On one hand, it suggests that not every elderly patient’s PRP preparation will be equally potent, a fact that could explain the notoriously inconsistent results of PRP clinical trials, where some patients respond robustly and others see little benefit. On the other hand, it opens a genuine opportunity for personalized medicine: rapid proteomic or functional screening of a patient’s PRP could, in principle, predict therapeutic quality before injection, or guide dosage and treatment protocols on an individual basis.

The study’s authors are careful about what their data do and do not establish. This is a characterization study, not a clinical trial; it demonstrates that elderly-derived PRP is rich in regenerative proteins and that its composition varies between people, but it does not yet prove that variations in the proteome translate into differences in healing outcomes for patients. Translating these molecular inventories into standardized, efficacy-graded PRP products will require correlating proteomic signatures with clinical endpoints in controlled studies, and the inter-individual variability the team documented is precisely the kind of biological signal that such trials should stratify for.

Still, the implications for an aging global population are considerable. As life expectancy rises, the burden of chronic wounds, osteoarthritis, tendinopathies, and other degenerative conditions grows with it, and the elderly are often the least well served by existing regenerative options. The new proteomic map provides reassurance that age does not strip PRP of its therapeutic cargo: even in advanced age, the platelet concentrate retains a wealth of proteins playing crucial roles in tissue regeneration. At the same time, it hands the field a molecular framework for moving beyond one-size-fits-all formulations toward personalized autologous therapies, where the composition of a patient’s own PRP becomes a measurable, and potentially optimizable, clinical variable. In a therapy long criticized for its biological opacity, that transparency may prove the most regenerative development of all.

The choice of activation agents in the study deserves particular attention, because it shapes what the mass spectrometer ultimately sees. Calcium gluconate mimics the physiological trigger for platelet activation, since rising intracellular calcium is the canonical signal that causes platelet granules to fuse with the cell surface and discharge their contents. Heparin, an anticoagulant, was used alongside it, and the combination allowed the researchers to drive degranulation in a controlled manner before removing the platelet bodies entirely. What remains after this step is the secretome: the soluble proteins, growth factors, and chemokines that would, in a living wound, be released directly at the site of injury. This design choice means the measured proteome approximates the bioactive payload a patient would actually receive, rather than an inventory of intact platelet contents.

The depletion of high-abundance proteins is equally consequential for interpreting the results. Albumin and immunoglobulins dominate blood plasma to such an extent that, undepleted, they can consume the vast majority of the mass spectrometer’s analytical capacity, drowning out low-copy signaling molecules. By removing them first, the team gained sensitivity into the mid- and low-abundance range where many regulatory proteins reside, including those governing extracellular matrix assembly and cell communication. This technical step helps explain why the study resolved nearly 1,400 distinct proteins, a depth of coverage that few earlier PRP characterizations achieved, and why proteins tied to vesicle transport and cytoskeletal dynamics emerged so prominently.

The finding that 324 proteins were detected only in platelet-rich plasma underscores how much the concentration step transforms the starting material. Platelets are not merely passive carriers; they are secretory cells whose alpha granules and dense granules hold a curated cargo accumulated during platelet production in the bone marrow. When activated, this cargo is released together with vesicles and microparticles that can deliver signaling molecules to target cells. The enrichment of vesicle transport proteins in the PRP samples is consistent with this biology, suggesting that the therapeutic effect of PRP may depend not only on soluble growth factors but also on the extracellular vesicles that platelets shed, which are increasingly recognized as mediators of intercellular communication in tissue repair.

The inter-individual variability documented across the 32 donors also invites reflection on its possible origins. Protein detection differences between donors could reflect genuine biological variation in platelet content, differences in circulating plasma proteins, or variation in how each donor’s blood responded to the preparation protocol. Age-related changes in platelet reactivity, chronic low-grade inflammation, comorbidities, and medication use are all plausible contributors in an elderly cohort, although the study design did not dissect these factors individually. What the data establish is that the variability itself concentrates in proteins associated with tissue regeneration, meaning the differences are not random noise scattered across irrelevant functions but are centered on the biology that matters therapeutically.

Methodologically, the work also contributes to reproducibility in a field often criticized for heterogeneity. The researchers reported quality control metrics including false discovery rate control for peptide and protein identification, and they deposited their data in the PRIDE proteomics repository, allowing other laboratories to reanalyze the raw spectra. Such transparency matters because PRP preparations differ widely across clinics in centrifugation protocols, activation methods, and platelet concentrations, making cross-study comparison difficult. A well-annotated molecular reference for elderly-derived PRP, produced under a documented preparation pipeline, gives the field a benchmark against which future formulations can be compared, and a foundation for the stratified clinical trials that will be needed to convert proteomic characterization into therapeutic guidance.

Subject of Research: Proteomic profiling of platelet-rich plasma from elderly individuals for autologous regenerative therapy

Article Title: Comprehensive proteomic profiling of platelet-rich plasma from elderly individuals: insights for autologous therapeutic applications

Article References: Buisan-Farré, A., Serra-Mas, M., Sarri, E., Salgado-Pacheco, V., Arauz-Garofalo, G., Odena-Caballol, A., Vilaseca, M., Gay, M., Ferrer-Solà, M., Masó-Albareda, C., Casals-Zorita, M., & Otero-Viñas, M. (2026). Comprehensive proteomic profiling of platelet-rich plasma from elderly individuals: insights for autologous therapeutic applications. Clinical Proteomics. https://doi.org/10.1186/s12014-026-09630-3

Image Credits: AI Generated

DOI: 10.1186/s12014-026-09630-3

Keywords: platelet-rich plasma, PRP, proteomics, mass spectrometry, elderly, tissue regeneration, regenerative medicine, autologous therapy, wound healing, coagulation, inter-individual variability, Clinical Proteomics