Regenerative Strategies in Empty Nose Syndrome: A Comparative Analysis of Microfat, Nanofat, SVF and Microfragmented Fat
Autologous Adipose-Derived Therapies for Empty Nose Syndrome: Structural and Regenerative Perspectives
What is ENS?
ENS was first described following inferior turbinate resections and was characterized by a paradoxical feeling of nasal congestion. Today, ENS is understood not only as an increase in anatomical space but also as a symptom of a paradoxical nasal obstruction.functional and neurosensory disordersIt is accepted that this is the case (Houser, 2007; Zhao et al., 2011). Patients experience disruption in the structure/volume of the turbinate tissue. Normally, the inferior turbinates, which are nearly cylindrical in shape and covered with ciliated nasal mucosa, play the most important role; however, they shrink, cool, or become scarred/fibrotic. In individuals with turbinates of normal anatomical structure, air entering the nose moves backward rotationally and slowly. During this movement, the air gradually warms, humidifies, cleans, and pressurizes. This requires warm turbinate tissue of normal size and a healthy mucosa with a warm mucus layer on its outer surface. Significant reduction or thermal damage to turbinates using devices such as radiofrequency, laser, cautery, electrocautery, and coblation, as well as permanent partial or near-total resection of turbinates through microdebrider reduction, turbinoplasty, and turbinectomy, can result in a serious decrease or impairment of nasal function. Patients may present to various physicians with a wide range of symptoms and findings, including accelerated airflow into the nose, contact of cold and dirty air with the pharynx and upper parts of the nose, nasal mucosal atrophy, altered secretion distribution and sticky nasal secretions, nasal dryness, changes in airways near the lungs, impaired sleep quality, and a feeling of shortness of breath.
The pathophysiological mechanisms in ENS include the following:
Disruption of the laminar flow of nasal air.
Loss of mucosal mechanoreceptor and trigeminal afferent function
Damage to the submucosal vascular network.
Chronic inflammation and fibrosis
Due to this multifaceted nature, volume replacement alone may not be sufficient in the treatment of ENS. Regenerative medicine practices become important at this point. Biological products derived from adipose tissue have many advantages in ENS patients due to their volume-enhancing and regenerative effects.
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| Adipose Tissue-Based Regenerative Approaches in Empty Nose Syndrome: The Clinical Role of Microfat, Nanofat, Stromal Vascular Fraction and Microfragmented Fat Tissue |
Adipose-Derived Regenerative Modalities in ENS: From Volume Restoration to Cellular Therapy
Adipose tissue, in high proportionadipose-derived stem cells (ADSC)It harbors a rich stromal vascular niche containing: Zuk et al. (2001) demonstrated that multipotent mesenchymal cells can be isolated from adipose tissue. These cells are:
Angiogenic (VEGF release)
Anti-inflammatory (IL-10, TGF-β modulation)
Antifibrotic
Neurotrophic factor producer
It exhibits these characteristics (Fraser et al., 2006; Kilroy et al., 2007).
In fibrotic and vascularly impaired tissues like ENS, these properties theoretically provide a therapeutic advantage. Adipose tissue is readily available, and patients can obtain the desired amount of adipose tissue-related biological products.
Microfat Applications
Microfat is a volume-enhancing lipoaspirate fraction obtained with minimal manipulation. Microfat is a biological product with a bulking effect. Microfat graft is a form of fat graft obtained by mechanically processing autologous adipose tissue following aspiration under low-traumatic conditions, preserving viable adipocytes and stromal vascular fraction (SVF) components. Fat aspiration is generally performed under low negative pressure, using 2–3 mm diameter cannulas and accompanied by tumescent techniques. The main goal of this approach is to maximize the preservation of adipocyte membrane integrity and cellular viability. The lipoaspirate obtained after aspiration is purified from blood, tumescent fluid, and cellular debris using methods such as sedimentation, filtration, or low-speed centrifugation.
Following the purification stage, microfat is reduced to a smaller particle size through a controlled mechanical breakdown process. This process is typically performed by transferring the microfat back and forth 20–30 times between two syringes via a 1–2 mm diameter connector. The aim is to reduce the size of the fat lobules, making them suitable for injection with thinner cannulas and ensuring a more homogeneous distribution within the tissue. Complete emulsification is not performed at this stage; therefore, unlike nanofat, microfat preserves viable adipocytes and maintains its bulking effect. If necessary, a more homogeneous suspension can be obtained by passing it through 500–800 micron filters.
Microfat grafts exhibit a dual effect in terms of both volume restoration and regenerative potential. The adipocytes they contain provide long-term volume support, while the SVF components (mesenchymal stem cells, pericytes, endothelial progenitor cells, and growth factors) support angiogenesis and tissue healing. Therefore, microfat is widely used in facial volume enhancement, atrophic scar treatment, and soft tissue defects. Furthermore, in fibrotic and volume-depleted nasal tissues, especially when applied at the submucosal level, it offers both mechanical support and biological healing potential.
When preparing microfat:
Between 10–20 cc injectors
Using a 1–2 mm connector adapter
The vehicle is moved back and forth 20-30 times.
Aim:
Shrinking fat lobules
To make it injectable with thinner cannulas.
To preserve adipocytes as much as possible.
⚠️ Full emulsification is not performed here (this is the difference from nanofat).
Filtration (Optional): It can be made more homogeneous by passing it through 500–800 micron filters. Although its bulking effect is more pronounced, it is not easy to inflate fibrotic and partially resected turbinate remnants with microfat. As seen in the nanofat injection video I shared in this article, if the turbinate structure is scarred or hardened/fibrotic, injecting a liquid into this tissue is very, very difficult. It's like injecting liquid into a burn wound on our skin 🙁
What is the Tumescent Technique in Liposuction?
Tmesan TechnicalIt is a surgical method, particularly used during liposuction, that involves infiltrating the target tissue with a large volume of diluted local anesthetic solution. The term "tumescent" refers to the tissue becoming tense and swollen (tumescent) after fluid infiltration.
In this technique generallyisotonic serum, in low concentrationlidocaineand due to its vasoconstrictor effectadrenaline (epinephrine)A solution containing [anesthetic] is used. This classically defined method has become widespread in dermatological surgery and has become a safe standard, especially in the field of liposuction. By administering a large volume but low concentration of anesthetic, the risk of systemic toxicity is reduced, while effective local anesthesia is provided over large areas.
The main physiological effects of tumescent infiltration are as follows:
Analyses:Lidocaine provides long-lasting local anesthesia.
Vasoconstriction:Adrenaline reduces bleeding and bruising.
Hydrodissection:Fluid infiltration separates the fat lobules, facilitating aspiration.
Reduced tissue trauma:Fat aspiration can be performed with lower negative pressure, which increases adipocyte viability.
In fat grafting procedures, especially when harvesting microfat and macrofat, the tumescent technique is important for preserving adipocyte integrity. When combined with low-traumatic aspiration, the long-term survival rate of the graft can be increased.
In clinical practice, tumescent technique is widely preferred in liposuction procedures because it reduces the need for general anesthesia, minimizes blood loss, and accelerates postoperative recovery.
For what purpose are microfats used?
Nasolabial filler
Cheek volumizing
under the eyes
Lips
Scar correction
Atrophic areas
Inferior turbinate submucosal volume enhancement in ENS cases (especially in fibrotic cases)
Microfat Injections Role at ENS
Microfat injections in ENS cases with inferior turbinate volume loss:
It can normalize nasal airflow.
It can reduce the Venturi effect.
It can increase mucosal surface contact.
Houser (2014) reported that submucosal filler applications improved symptom scores. There is no standardized treatment protocol for ENS. In turbinates with volume loss, microfat injection is not easy if the existing remnant turbinate tissue is finbrotic or scarred. Although injection is usually done using a cannula, microfat injection can be done in limited amounts in remnant turbinates that have turned into scar tissue.
Microfat andAdvantages
In patients with ENS, myctofat injections offer several advantages, including:
Technically feasible.
Autogen material
Fast volume effect
Disadvantages of Microfat
In patients with ENS, the following disadvantages exist regarding myctofat injections:
Resorption (reported to be between 20–50%)
Because vascularization is poor in fibrotic tissue, graft survival may be reduced, and injection is also difficult in fibrotic tissues.
Nanofat Applications
Nanofat is another biological product obtained from adipose tissue.Tonnard et al. (2013) showed that when obtained by mechanical emulsification, it carries regenerative potential rather than volumetric effect.
Nanofat Mechanism
During the production of this biological product, adipose tissue undergoes finer filtration, and while fat cells are damaged during the process, regenerative properties come to the forefront. After mechanical processing, fragments of matrix components such as collagen, laminin, fibronectin, and proteoglycans are found. These create a microenvironment that supports cellular migration and the regenerative process. Since adipocytes are largely broken down during nanofat preparation, cell membrane remnants, lipid droplets, and cytoplasmic content may be present. Therefore, nanofat exhibits biostimulatory rather than bulking properties. If nanofat is prepared in combination with PRP, platelet-derived growth factors and additional cytokines are also added to the content.
The most important part of nanofatSVF (Stromal Vascular Fraction)It is. Within this faction:
Adipose-derived mesenchymal stem cells (ADSC)
Pre-adipositler
Pericytes
Endothelial cells
Fibroblasts
Macrophages
hematopoietic cells
It is found.
While most adipocytes are destroyed during mechanical emulsification, these stromal cellular components are preserved. This cell population is the main source of the regenerative effect.
Nanofat contains many biologically active molecules released from the cellular and extracellular environments:
VEGF (Vascular Endothelial Growth Factor)
TGF-β (Transforming Growth Factor Beta)
PDGF (Platelet Derived Growth Factor)
HGF (Hepatocyte Growth Factor)
IGF (Insulin-like Growth Factor)
These molecules:
Angiogenesis
Fibroblast activation
Collagen synthesis
Tissue remodeling
Anti-inflammatory effect
plays a role in it.
Nanofat:
poor in live adipocytes
SVF and stem cell rich
Containing growth factor
It is regenerative biological material.
Nanofat Applications:
Skin rejuvenation
Scar treatment
Radiation damage
Fibrotic tissues
Atrophic mucous membranes (e.g., experimental applications in cases of empty nose syndrome)
It is preferred in areas such as these.
In fibrotic ENS tissue, it could theoretically contribute to collagen reorganization.
Nanofat in ENS TreatmentAdvantages
Nanofat injectionEspecially in the treatment of Empty Nose Syndrome (ENS)in inferior or middle turbinate tissue that has developed atrophic, fibrotic and volume lossIt is attracting attention due to its biological regeneration potential. Unlike classic filler materials, nanofat is more of a bulking agent than a bulking agent.regenerative and biostimulatoryThis feature provides a more physiological approach to the components involved in ENS pathophysiology, such as mucosal atrophy, submucosal fibrosis, neurosensory dysfunction, and microvascular insufficiency.
The most important advantage of nanofat is,stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cells (ADSC)It is the content. These cellular components;angiogenesis, collagen remodeling, anti-inflammatory effect, and neurotrophic support.This can provide support. Mucosal dryness and epithelial thinning, frequently observed in ENS patients, are associated with decreased vascular support. Growth factors (VEGF, HGF, TGF-β, etc.) in nanofat content can support mucosal trophism by increasing microvascular density. This theoretically contributes to improved mucosal hydration and barrier function.
Another important advantage is,remodeling potential in fibrotic tissueIn ENS, submucosal scarring and rigidity, particularly after aggressive turbinectomy, can disrupt the laminar distribution of airflow, leading to a paradoxical feeling of obstruction. Mesenchymal cells and cytokines in the nanofat content may contribute to making fibrotic tissue more flexible through TGF-β modulation and matrix remodeling. This can help improve mucosal compliance and a more physiological perception of airflow.
Another advantage of nanofatit is autologousCompared to alloplastic implants or synthetic fillers, they carry a lower risk of foreign body reaction, chronic inflammation, and infection. They also have the potential for tissue integration, which is important for long-term biocompatibility. In chronic and multifactorial conditions like ENS, the preference for biological materials can reduce the need for revisions.
Finally, nanofat injection is not for the purpose of increasing volume,with the aim of improving mucosal qualityBecause it is applicable, it can be combined with microfat, PRP, or other biological agents. This combination approach offers the possibility of achieving both structural and regenerative goals in the same session in ENS treatment.
Of course, data on nanofat applications for ENS in the current literature are limited and mostly based on small case series. However, considering the pathophysiological mechanisms, it can be considered a promising biological option, especially in patients with fibrotic and atrophic turbinate tissue.
Nanofat in ENS TreatmentDisadvantages
Nanofat injectionAlthough it is interesting due to its biological and regenerative potential in the treatment of Empty Nose Syndrome (ENS), it has some important disadvantages and limitations.
First and foremost, the most fundamental disadvantage is,volume stability is unpredictable.Since a large portion of the adipocytes are fragmented during nanofat preparation, the sustained volume effect is lower compared to classic microfat or macrofat grafts. In ENS patients, especially those with significant turbinate volume loss, nanofat application alone may not provide sufficient mechanical strength or aerodynamic correction. Therefore, additional bulk-donating materials may be required for structural support in most cases.
The second major disadvantage is,the literature is limitedStudies on the use of nanofat in ENS are generally at the level of small case series or experimental approaches. Long-term follow-up data, standard dosing protocols, and optimal injection plans are not yet clear. This makes it difficult to predict treatment efficacy and manage patient expectations.
Another problem,post-injection edema and transient inflammatory responseIt is possible for it to develop. ENS patients are already hypersensitive to nasal airflow. Transient mucosal swelling or irregular surface formation can briefly increase the feeling of paradoxical obstruction. In addition, the inability of the injection to distribute homogeneously in the submucosal fibrotic area can lead to irregular tissue thickening.
Furthermore, the regenerative effect of nanofat largely depends on cellular viability. Mechanical trauma during processing can create variability in cellular density and viability. Lack of standardization can lead to differing results between centers.
Finally, it should be noted that the pathophysiology of ENS is not limited to volume and mucosal atrophy alone. Neurosensory dysfunction and central perception mechanisms also contribute to the condition. Nanofat may not fully correct this complex neurosensory component; therefore, it should not be considered a "curative" approach on its own.
Stromal Vascular Fraction (SVF)
SVF is a heterogeneous cell population obtained by enzymatic or mechanical methods. ADSC includes endothelial progenitor cells and immune cells (Bourin et al., 2013).
Stromal Vascular Fraction (SVF)It is a heterogeneous cellular fraction obtained from adipose tissue and contains adipose-derived mesenchymal stem cells (ADSC), pericytes, endothelial cells, fibroblasts, macrophages, and various progenitor cells.
Obtaining an SVF generally involves the following steps:
Obtaining fat tissue through liposuction.
Low negative pressure aspiration is usually performed from the abdominal or femoral region.Processing of fat tissue
There are two main methods:Enzymatic method (digestion via collagenase):
Lipoaspirate is incubated with collagenase, then centrifuged. Adipocytes remain in the supernatant while the cellular fraction separates into a sub-pellet. This pellet forms the SVF.Mechanical method (without enzymes):
The stromal cellular content is concentrated through emulsification, filtration, and centrifugation processes. Cellular yield may be lower compared to the enzymatic method, but it is more practical in terms of regulation.Centrifugation and washing stage
The cell pellet is separated from the supernatant and usually washed with saline to prepare it for injection.
Enzymatic methods offer a higher yield of cellular products, but may be subject to advanced cellular product regulations in many countries.
Advantages of SVF in ENS Treatment
SVF offers a biologically based approach, particularly in the treatment of Empty Nose Syndrome (ENS). The pathophysiology of ENS involves not only volume loss but also mucosal atrophy, fibrosis, microvascular reduction, and neurosensory dysfunction. The advantage of SVF lies in its focus on this multi-component structure.
Angiogenic Effect and Mucosal Trophism
Endothelial progenitor cells and ADSCs within the SVF secrete various growth factors, primarily VEGF. This situation:
Increased microvascular density
Improvement of mucosal nutrition.
Improved epithelial quality
This is a significant advantage in terms of mucosal dryness and trophic insufficiency seen in ENS.Trophic insufficiency, one tissue is sufficientnutrition (blood supply), oxygenation and biological supportIt is a condition in which the body weakens structurally and functionally as a result of its inability to absorb nutrients. The word "trophic" comes from Greek.trophy(It is) of nutritional origin and refers to the support mechanisms necessary for the tissue to maintain its viability.
Anti-inflammatory and Immunomodulatory Effects
ADSC’ler:
It modulates pro-inflammatory cytokines such as TNF-α and IL-1β.
It can direct macrophage polarization towards the M2 phenotype.
This can contribute to the suppression of the chronic inflammatory process. It offers potential benefits in terms of mucosal irritation and neuroinflammatory components frequently seen in ENS patients.
Remodeling in Fibrotic Tissue
In ENS, submucosal scar tissue, especially after aggressive turbinectomy, can impair airflow perception. Mesenchymal cells within the SVF:
It can modulate TGF-β signaling pathways.
It can support extracellular matrix remodeling.
This can increase tissue elasticity and improve mucosal compliance.
Neurotrophic Potential
ADSCs have been shown to secrete neurotrophic factors. Considering neurosensory dysfunction in the ENS, theoretically:
Support of mucosal nerve endings
Improving airflow perception
It can provide contributions such as these. However, this field is still at the experimental stage.
Being autologous and biologically compatible.
SVF is obtained entirely from the patient's own tissue. Therefore:
The risk of foreign body reaction is low.
It has high integration potential.
It has the advantage of biocompatibility compared to alloplastic materials.
SVF is not only about increasing volume in ENS,a regenerative approach aimed at improving mucosal quality and biological functionIt offers [certainty/status]. However, long-term, randomized controlled trials are limited, and application protocols are not standardized.
Disadvantages of SVF in ENS Treatment
Stromal Vascular Fraction (SVF)Although it is a theoretically promising biological option in the treatment of Empty Nose Syndrome (ENS) due to its regenerative potential, it has some important disadvantages and limitations.
First and foremost, the most important problem is,the level of scientific evidence is limitedPublications on the use of SVF in ENS are generally small case series or experimental in nature. Randomized controlled trials, long-term outcomes, and standardized protocols are not yet sufficient. Therefore, there is no clear consensus on efficacy, sustainability, and optimal dosage. In a multifactorial disease like ENS, predicting treatment success can be challenging.
The second major disadvantage is,regulations and legal restrictionsEnzymatically obtained SVF is considered outside the scope of "minimal manipulation" in many countries and may fall into the category of advanced cellular therapy products (ATMP). This brings with it ethical committee, laboratory infrastructure, and licensing requirements for clinical practice. Although mechanical methods are more practical, they can vary in terms of cellular density and viability.
From a technical point of view, obtaining SVFrequires additional liposuction procedure.This prolongs the operation time and increases the risk of donor site morbidity (hematoma, seroma, pain, infection). Since a significant portion of ENS patients have undergone multiple surgeries previously and are psychologically vulnerable individuals, additional procedures may affect patient compliance.
Another disadvantage is,the volumetric efficiency is limitedSVF primarily exerts cellular and biostimulatory effects; it does not provide significant structural support. However, in ENS, mechanical volume restoration for aerodynamic improvement can be critical, especially in cases with severe turbinate resection. Therefore, SVF is generally insufficient on its own and may need to be combined with microfat or structural implants.
Furthermore, the biological behavior of cellular products.unpredictabilityIt may include factors such as cell viability, preparation technique, injection level, and recipient bed vascularity. Cell uptake may be low in excessively fibrotic tissue. Theoretically, the risk of uncontrolled fibrotic response or irregular tissue thickening should also not be ignored.
Finally, an important component of ENS pathophysiology.neurosensory dysfunction and central perception changesThis may not fully resolve with peripheral regenerative treatments alone. Even if SVF can improve mucosal trophism, the patient's subjective feeling of air hunger may not completely disappear.
In summary, while SVF ENS treatment offers a biologically rational approach, it necessitates careful patient selection and combined treatment strategies due to a lack of evidence, regulatory challenges, insufficient volumetric capacity, and unpredictable outcomes.
Microfragmented Fat Tissue
Microfragmented adipose tissue, obtained by mechanical fragmentation in closed systems, preserves the vascular niche. This is one of the best-known systems.Lipogems'Yes.
Positive results have been reported in the literature regarding orthopedic and wound healing applications (Bianchi et al., 2018).
Microfragmented adipose tissue (MFAT)lipoaspiratewithout using enzymesin closed and sterile systemsmechanical disintegration and washingThis is achieved by targeting a portion of the adipocytes, and especially...stromal vascular fraction (SVF)The goal is to obtain a fat suspension that is free of inflammatory residues, contains small particles, but maintains its structural integrity while preserving its content.
The steps involved in obtaining it can be summarized as follows:
Removal of fat tissue with low-pressure liposuction.
Aspiration is usually performed using a tumescent technique from the abdominal or femoral region.Mechanical microfragmentation in a closed system.
Fat tissue is physically broken down within special filter and ball systems.Most adipocytes are preserved.
SVF cells are retained within the stromal matrix.
Blood and fat phase residues are removed.
Washing and purification
The product obtained is free of free lipids, blood, and inflammatory residues, and has a more homogeneous particle size.
This method, unlike enzymatic SVF isolation, is considered to fall under the category of "minimal manipulation" and better preserves cellular-matrix integrity.
Advantages of MFAT in ENS Treatment
MFAT is particularly useful in the treatment of Empty Nose Syndrome (ENS) both.volume restorationhim theregenerative effectIt is noteworthy because it can be presented together.
Both Structural and Biological Effects
One of the main problems in ENS is turbine volume loss. MFAT:
It provides mechanical volume thanks to its adipocyte content.
It generates biostimulation through stromal cells and growth factors.
This dual effect may offer a more balanced approach compared to nanofat or isolated SVF.
Preservation of the Stromal Matrix
In microfragmented adipose tissue, the extracellular matrix (ECM) structure is preserved. This means:
It can increase cell retention in the recipient tissue.
It can promote vascularization.
It can provide more physiological remodeling in fibrotic tissue.
Submucosal fibrosis and mucosal rigidity are significant problems in ENS; the matrix-supported structure of MFAT can help improve tissue elasticity.
Angiogenesis and Mucosal Trofism
ADSCs and pericytes within MFAT:
It releases VEGF and other growth factors.
It can increase microvascular density.
This situation may contribute to the improvement of mucosal quality in ENS patients with mucosal dryness and trophic insufficiency.
Improved Volume Stability
Because adipocyte integrity is better preserved compared to nanofat:
The resorption rate may be lower.
A more stable concha simulation can be achieved from an aerodynamic point of view.
This is especially important in cases where advanced resection has been performed.
Lack of Enzyme Use
Because it does not require enzymatic processing:
It is more practical from a regulatory point of view.
The risk of cellular manipulation is lower.
It facilitates clinical application.
MFAT in ENS treatment:
Structural volume restoration
Improvement of mucosal quality
Angiogenic and anti-inflammatory support
It can be considered as a combined biological material capable of providing...
However, long-term results are limited, and biological approaches alone may not be sufficient in ENS cases with a significant neurosensory component. Therefore, patient selection, injection planning, and combined biological approaches, if necessary, are important.
Disadvantages of MFAT in ENS Treatment
Microfragmented Fat Tissue (MFAT)Although it can be considered a rational option in the treatment of Empty Nose Syndrome (ENS) due to both its volume-enhancing and regenerative effect potential, it has some significant disadvantages.
Firstly, Resorption and volume stability are unpredictable.Although a significant proportion of adipocytes are preserved in MFAT, graft engraftment may be variable in areas with relatively limited vascularity, such as the nasal cavity, and those previously subjected to surgical trauma. Neovascularization may be delayed, particularly in severely fibrotic and scarred submucosal tissue, leading to volume loss. Therefore, the permanence of aerodynamic correction in ENS is not guaranteed.
The second major disadvantage is,There is a risk of temporary obstruction sensation and edema after injection.ENS patients are hypersensitive to airflow perception. Edema, mucosal surface irregularities, or increased local pressure that may occur after submucosal MFAT injection can increase the paradoxical feeling of obstruction in the short term. This may be particularly pronounced in patients with high anxiety levels.
Another problem,it requires technical precisionInjection level, particle size, and distribution homogeneity are critically important. Superficial injection may cause mucosal swelling and irregularities, while very deep injection may not provide sufficient aerodynamic effect. Furthermore, since the anatomical structure of the turbinate remnants varies from person to person, there is no standard application protocol.
While the absence of enzyme use is advantageous in terms of regulation, it also affects cellular content and viability rate.It is not standardized.The preparation system, mechanical procedure time, and surgeon's experience can all affect the results. This can lead to differences in outcomes between centers.
Finally, regarding the pathophysiology of ENS...neurosensory dysfunction and central perception changesThis condition may not fully resolve with peripheral volume and biological improvement alone. Even if MFAT improves mucosal quality and volume, the patient's subjective feeling of "air hunger" may persist. Therefore, it should be considered not as a curative treatment on its own, but as part of a multimodal approach.
Biologic Reconstruction in Empty Nose Syndrome: The Emerging Role of Adipose Tissue-Based Treatments and Comparison
Empty Nose Syndrome (ENS) is a complex clinical condition characterized not only by turbinate volume loss but also by mucosal atrophy, fibrosis, microvascular reduction, and neurosensory dysfunction. Therefore, treatment aims not only at mechanical volume restoration but also at improving mucosal trophism and biological function. In recent years...nanofat, microfat, stromal vascular fraction (SVF), and microfragmented adipose tissue (MFAT)Autologous adipose tissue-based approaches, such as these, have come to the forefront within the context of ENS.
NanofatIt is mechanically emulsified and filtered adipose tissue; it is poor in adipocytes and relatively rich in stromal cells and growth factors. Its most important advantage in ENS is its potential to improve mucosal quality, support angiogenesis, and remodel in fibrotic tissue. It can provide a biostimulatory effect, especially in atrophic and trophically deficient mucosa. However, it does not provide significant volume support and has a high resorption rate. Therefore, it may not be sufficient on its own in patients with advanced turbinate resection.
MicrofatThis is a fat graft with larger particles and preserved adipocyte integrity. Its most important advantage in ENS is mechanical volume restoration; it can contribute to the redirection of airflow. However, the regenerative cellular content is lower compared to nanofat or SVF. Furthermore, the dependence of the resorption rate and graft retention on the vascularity of the recipient bed is a significant disadvantage. Excessive volume application can increase the paradoxical feeling of obstruction.
Stromal Vascular Fraction (SVF)This is the cellular fraction isolated by enzymatic or mechanical methods and includes ADSCs, pericytes, and endothelial cells. In ENS, it is theoretically the most powerful biological approach in terms of mucosal trophism, anti-inflammatory effect, and potential neurotrophic support. However, its volumetric effect is minimal, and it is insufficient on its own in cases of severe structural loss. Furthermore, enzymatic isolation is subject to regulatory restrictions in many countries, and application protocols are not standardized.
Microfragmented Fat Tissue (MFAT)This is an enzyme-free product that protects both adipocytes and stromal cells within the matrix structure. Its most significant advantage from an ENS perspective is its ability to provide both structural volume and biological support. Preserving the stromal matrix can enhance cell uptake and vascularization. However, resorption is unpredictable, uptake in the fibrotic area can be variable, and transient edema after injection can exacerbate paradoxical symptoms.
In conclusion, each of these biological approaches in ENS treatment targets different goals:
Nanofat and SVF are more common.regenerative and mucosal quality enhancing,
Microfat is moremechanical volume restorative,
MFAT ishybrid (structural + biological)It is an option.
However, the current literature is limited, and it cannot be said that a single method is a universal solution without considering patient selection, the status of turbinate remnants, the degree of fibrosis, and the neurosensory component. In ENS, biological adipose tissue applications should generally be considered as part of a multimodal approach.
Sources:
Zuk PA et al. Multilineage cells from human adipose tissue. Tissue Eng. 2001.
Fraser JK et al. The biology of adipose-derived stem cells. Cytotherapy. 2006.
Kilroy GE et al. Cytokine profile of human adipose-derived stem cells. J Cell Physiol. 2007.
Tonnard P et al. Nanofat grafting: basic research and clinical applications. Plast Reconstr Surg. 2013.
Bourin P et al. Stromal vascular fraction: definition and clinical use. Cytotherapy. 2013.
Houser SM. Surgical treatment for empty nose syndrome. Laryngoscope. 2007 & 2014.
Zhao K et al. Computational fluid dynamics in ENS. J Biomech. 2011.
Gentile P et al. Combined fat grafting and regenerative approaches. Stem Cell Res Ther. 2017.
Bianchi F et al. Microfragmented adipose tissue in regenerative medicine. Int Orthop. 2018.
Hayakawa K et al. Adipose stem cells and mucosal healing. Stem Cells Transl Med. 2015.
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