ADSCs are a multipotent cell population residing within the SVF of adipose tissue. They possess the capacity for self-renewal and multilineage differentiation, including adipogenic, osteogenic, chondrogenic, and myogenic lineages^[18]. ADSCs also exert potent paracrine effects by secreting a wide array of growth factors, cytokines, and extracellular vesicles, which collectively promote angiogenesis, modulate immune responses, and support tissue repair^[19,20]. These properties have positioned ADSCs as a key cellular component in regenerative medicine^[21]. SVF is a foundational cellular derivative that is typically isolated from adipose tissue by enzymatic digestion. It comprises a heterogeneous cell population that includes ADSCs, endothelial cells, pericytes, and immune cells. However, the composition and therapeutic potential of SVF are highly sensitive to processing methods. Procedures such as tissue washing can markedly alter the proportion of blood-derived cells, thereby affecting subsequent cellular activity and culture outcomes^[22]. In addition to enzymatically isolated SVF, mechanical processing techniques have gained increasing attention for the isolation of tissue stromal vascular fraction (tSVF), which preserves the native ECM together with cellular components. Mechanical approaches, including filtration and centrifugation, can effectively disrupt adipocytes and enrich for regenerative tSVF, which has shown particular promise in pro-inflammatory conditions such as osteoarthritis^[23,24].

Nanofat is a mechanically processed adipose tissue derivative generated through purely physical emulsification and filtration, resulting in a liquid suspension containing extremely small tissue fragments devoid of intact adipocytes. The typical preparation protocol involves harvesting fat via standard liposuction, followed by mechanical emulsification through repeated passage between two syringes connected by a small-bore connector, and finally filtration to remove coarse fibrous components^[25,26]. This process selectively disrupts mature adipocytes while theoretically preserving the SVF, including ADSCs, endothelial cells, and pericytes, along with some ECM components^[27].

Unlike conventional fat, nanofat is too liquid to serve as a volumetric filler. Instead, its therapeutic value lies in its paracrine activity and cellular components. Studies have demonstrated that nanofat retains viable ADSCs and other progenitor cells capable of proliferation and differentiation^[28]. Moreover, nanofat secretes a rich cocktail of growth factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF), which collectively promote angiogenesis, modulate inflammation, and stimulate dermal remodeling^[29]. These properties make nanofat particularly suitable for indications requiring biological regeneration rather than volume augmentation, such as skin rejuvenation, scar treatment, and periorbital hyperpigmentation^[30].

SVF-gel, also known as stromal vascular fraction gel, is an advanced adipose tissue derivative that combines the cellular components of the SVF with the native ECM^[20]. Its injectable, gel-like consistency represents a transitional product between cell-rich suspensions (such as SVF and nanofat) and matrix scaffolds, offering both biological activity and minimal structural support for soft tissue regeneration^[31]. SVF-gel is typically prepared through mechanical processing of lipoaspirates without the addition of exogenous enzymes^[32]. The most established protocol involves emulsification of harvested adipose tissue by repeated passage between two syringes, followed by centrifugation at a specific speed. This process disrupts mature adipocytes, releases their lipid content, and concurrently concentrates the cellular and ECM components into a viscous gel phase^[33]. The injectable gel is enriched with ADSCs, endothelial cells, pericytes, and a preserved ECM framework, while largely devoid of the lipid content^[32]. SVF-gel possesses several distinctive structural and biological properties: its gel-like consistency allows for injection through fine needles (as small as 25-27 gauge), enabling precise delivery and minimally invasive application; the preservation of native ECM provides a supportive microenvironment for the embedded cells, enhancing their survival, retention, and paracrine function following transplantation; and the removal of most lipid components reduces the inflammatory burden associated with necrotic adipocytes, thereby minimizing complications such as cyst formation and calcification^[34,35]. Studies have shown that SVF-gel retains viable ADSCs that maintain their differentiation capacity and secrete a range of pro-angiogenic and immunomodulatory factors, including VEGF, HGF, and transforming growth factor-beta (TGF-β)^[36].

CEFFE is an acellular, bioactive extract obtained from adipose tissue through a process that removes adipocytes, stromal cells, and large structural components while preserving soluble growth factors, cytokines, chemokines, and other functional proteins^[37,38]. The preparation typically involves harvesting lipoaspirates, followed by sequential centrifugation to eliminate lipids and cellular debris and final filtration through a filter to obtain the CEFFE product^[39,40]. CEFFE contains no viable cells, a feature that minimizes immunogenicity and reduces the risks associated with transplantation, while also allowing for potential allogeneic application and off-the-shelf storage^[41]. The extract retains a complex mixture of growth factors, including VEGF, HGF, bFGF, and TGF-β, as well as other adipose-derived soluble trophic proteins, which collectively promote angiogenesis, immunomodulation, and tissue repair^[42]. Although extracellular vesicle-associated components may be present depending on the preparation protocol, CEFFE is not a purified exosome or extracellular vesicle product; therefore, a defined vesicle size range cannot be assigned to CEFFE as a whole, and its bioactivity should be attributed mainly to its complex soluble protein and growth-factor profile. As a liquid product, CEFFE can be administered via injection or topical application, making it particularly suitable for regenerative interventions such as skin rejuvenation, wound healing, and anti-inflammatory therapy^[43]. Its regenerative potential is mediated primarily by bioactive proteins and soluble factors, enhancing collagen synthesis, cell migration, and tissue remodeling without relying on the proliferation or differentiation of viable cells^[37]. CEFFE thus represents a cell-free adipose tissue derivative that emphasizes the role of soluble bioactive factors in tissue regeneration, complementing other adipose-derived products such as SVF, Nanofat, and SVF-gel in the context of regenerative medicine^[44,45].

AMC is a high-rigidity, collagen-rich adipose-derived material prepared through a purely mechanical filtration and dehydration process, representing a specialized derivative designed for structural support and volume augmentation in soft tissue reconstruction^[46]. The preparation protocol begins with harvesting lipoaspirates, followed by centrifugation to obtain Coleman fat or high-density fat (HDF), which is then passed through a filtering device consisting of a sleeve and three internal sieves with a 1.5 mm filter-screen spacing^[47]. The tissue retained on the sieves is collected and subsequently dehydrated in a 100-mesh filter bag, surrounded by gauze, until no obvious liquid droplets fall during forceps pickup, yielding the final AMC product^[48].

AMC possesses several distinctive structural and mechanical properties that differentiate it from conventional fat grafts. Histological analysis (hematoxylin/eosin and Masson’s trichrome staining) has demonstrated that AMC contains significantly higher levels of ECM and collagen fibers compared to Coleman fat, with electron microscopy confirming the presence of dense fibrous connective tissue^[49]. Quantitatively, the collagen content of AMC is 45% ± 3.2%, which is markedly higher than the 15% ± 3.5% found in Coleman fat (P < 0.01). Correspondingly, the stiffness of AMC, measured at 6.1 ± 0.83 kPa, is substantially greater than that of Coleman fat at 1.9 ± 0.22 kPa (P < 0.01). Notably, AMC contains fewer viable cells than Coleman fat, indicating that its regenerative and volume-retention effects are mediated primarily through matrix-dependent mechanisms rather than cellular activity^[16,48].

The regenerative efficacy of AMC has been evaluated in preclinical models. In nude mouse transplantation studies, AMC demonstrated a volume retention rate of 75% ± 7.5% at 90 days post-grafting, which was significantly higher than the 42% ± 13.5% retention rate observed for Coleman fat (P < 0.05)^[48]. Moreover, AMC maintained a stable higher stiffness throughout the observation period, whereas Coleman fat exhibited progressive loss of mechanical integrity^[49]. These findings suggest that AMC is particularly suitable for clinical applications requiring rigid structural support, such as facial contouring, nasal augmentation, chin enhancement, and deep soft tissue filling, where traditional fat grafts often fail to provide adequate projection and long-term volume stability. As a mechanically processed derivative without enzymatic treatment, AMC offers the advantages of simplified regulatory pathways and point-of-care availability, positioning it as a promising biomaterial for precision fat grafting in structural reconstruction^[50].

ACF is a novel adipose-derived ECM concentrate prepared through a purely mechanical processing technique involving pulverization, filtration, and centrifugation^[51]. It represents a collagen-based scaffold that retains native matrix components while eliminating viable cells^[52]. The typical preparation protocol begins with harvesting lipoaspirates, followed by centrifugation to generate Coleman fat, which is then washed, homogenized, sequentially filtered through mesh screens of decreasing pore sizes (e.g., 0.25 or 0.15 mm), and finally centrifuged at higher speed to collect the solid portion as ACF^[52]. ACF is characterized as an adipokine-enriched, sustained-release collagen scaffold that retains high levels of collagen I, collagen IV, and laminin, while containing nonviable cells^[52]. Proteomic analysis has revealed that ACF contains diverse adipogenic and angiogenic proteins, including components involved in lipid metabolism, angiogenesis, antioxidant defense, and cell proliferation^[53]. Unlike viable cell-containing derivatives such as SVF or nanofat, ACF exerts its regenerative effects primarily through matrix-mediated mechanisms, providing structural support and sustained release of bioactive factors that promote host cell recruitment, adipogenesis, and neovascularization. Preclinical studies have demonstrated that ACF promotes soft tissue regeneration, wound healing, and volume retention. It offers advantages for off-the-shelf availability, reduced regulatory complexity, and improved storage stability, making it a promising platform for translational applications in regenerative medicine.

adECM, also known as decellularized adipose tissue (DAT), decellularized adipose matrix (DAM), and acellular adipose matrix (AAM), is an acellular scaffold produced by removing cellular and lipid components from adipose tissue while preserving the native ECM architecture and bioactive cues^[54]. The decellularization process typically involves a combination of physical, chemical, and enzymatic treatments, including repeated freeze-thaw cycles, mechanical agitation, treatment with detergents, and nuclease digestion to remove cellular debris and nuclear material^[55]. The resulting product is a three-dimensional, porous scaffold composed primarily of collagen, elastin, glycosaminoglycans, and various growth factors bound to the matrix, such as VEGF, bFGF, and TGF-β^[56,57].

adECM possesses several critical properties that make it an ideal scaffold for tissue engineering. First, it retains the native three-dimensional biomechanical characteristics of adipose tissue, providing a physiologically relevant microenvironment for cell attachment, migration, and differentiation^[58]. Second, the preserved bioactive components, including matricellular proteins and growth factors, actively direct host cell behavior by promoting adipogenesis, angiogenesis, and immunomodulation^[59]. Third, as an acellular product, adECM eliminates concerns related to immunogenicity and disease transmission associated with allogeneic or xenogeneic cellular components, while also offering the advantages of off-the-shelf availability and prolonged storage stability^[60].

The regenerative potential of adECM is attributed to its retained proteomic profile, which includes proteins involved in lipid metabolism, ECM organization, and tissue remodeling. Studies have demonstrated that adECM can recruit host ADSCs and direct their differentiation toward the adipogenic lineage, as indicated by the upregulation of key regulators such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα)^[61]. In vivo implantation studies have shown that adECM promotes vascularized adipose tissue regeneration, with newly formed adipocytes appearing within the scaffold as early as two weeks post-implantation. The scaffold gradually degrades over time, being replaced by host-derived, functional adipose tissue that integrates with the surrounding native tissue.

ADF is an innovative autologous ECM-based bio-membrane fabricated through a simple physical compression process inspired by traditional papermaking technology^[62]. It transforms clinically discarded adipose tissue into a ready-to-use, cell-free membrane that preserves native ECM bioactivity while providing favorable mechanical properties and storage stability^[63]. The preparation protocol involves harvesting autologous adipose tissue via liposuction or abdominal surgery, followed by sequential crushing and washing to remove lipids, blood components, and cellular debris while preserving native ECM architecture. Finally, mechanical pressing forms a cohesive, thin, pliable film. Histological analysis confirmed effective removal of nuclei and lipids, while ADF retains key ECM components, including collagen (types I, III, and IV), elastin, and glycosaminoglycans, as well as bound growth factors^[64].

ADF exhibits several advantageous properties for tissue regeneration. Its flexibility allows for easy handling, cutting, and application to wound beds or defect sites. Mechanical testing demonstrates that ADF exhibits a typical J-shaped stress-strain curve and maintains structural integrity during handling^[65]. Its dense collagenous structure provides a physical barrier against bacterial invasion and fluid loss while permitting gas exchange^[66]. Importantly, ADF can be cryopreserved at -80 °C without functional compromise (frozen ADF, F-ADF), with proteomic analysis confirming the remarkable stability of proteins after 12 months of storage^[67]. Moreover, ADF acts as a bioactive substrate that supports the adhesion, proliferation, and migration of various cell types and promotes adipogenic differentiation^[68]. In vivo studies have demonstrated that ADF promotes wound healing and soft tissue regeneration, partly through angiogenesis-related mechanisms involving the recruitment of monocytes that differentiate into macrophages, which serve as central regulators of angiogenesis^[69]. As an autologous, cell-free product, ADF offers the advantages of low immunogenicity, reduced regulatory burden, and off-the-shelf potential for manufacturing, while its capacity for long-term cryopreservation enables the establishment of personalized “ECM banks” for future regenerative applications^[70].

AAF is an adECM-based bio-membrane, which transforms human adipose tissue into a ready-to-use, cell-free film. It exhibits dry-state toughness and wet-state plasticity, allowing close adaptation to tissue expanders and irregular wound surfaces^[71]. The preparation protocol involves decellularization of human adipose tissue aspirates to remove cellular components, followed by freeze-drying and mechanical grinding to convert the material into powder form. The powder is digested in hydrochloric acid and pepsin solution to form a pre-gel solution, which then transforms into a hydrogel state^[72,73]. Finally, the hydrogel is cast into a mold and dried at low temperature to form the AAF membrane. Mechanical property tests demonstrate that AAF does not fracture when repeatedly folded and curled in the dry state, indicating high strength and toughness under moisture-free conditions^[74]. However, upon contact with tissue fluid, the material rapidly absorbs fluid and becomes soft enough to tightly fit and adhere to the dilation capsule, exhibiting excellent swelling capacity and deformation adaptability in wet environments^[75].

AAF exhibits several advantageous properties for tissue regeneration. Its dry-state toughness enables easy handling, sterilization, and storage, while its wet-state plasticity allows conformable adaptation to underlying structures^[76]. In vitro studies have demonstrated that AAF significantly promotes the proliferation and migration of skin cells, vascular endothelial cells, and ADSCs. Moreover, AAF enhances the adipogenic differentiation of ADSCs^[74]. In a rat skin expansion model, AAF significantly improved skin expansion efficiency while reducing skin retraction. Histological analysis revealed that AAF increased skin thickness and dermal collagen content, facilitating skin renewal and enhancing expansion efficiency. Furthermore, AAF significantly enhanced local blood flow and promoted neovascularization. Notably, AAF was also found to promote subcutaneous adipose tissue regeneration^[77]. As a decellularized, cell-free product, AAF offers the advantages of reduced immunogenicity, sustained release of ECM-derived bioactive factors, and the ability to provide both mechanical support and biological stimulation for skin and soft tissue regeneration, making it a promising biomaterial for tissue expansion and reconstructive surgery.

In wound healing, adipose-derived products mainly function through angiogenesis, inflammation regulation, fibroblast activation, epithelialization, ECM remodeling, and restoration of tissue perfusion.

SVF is one of the most frequently studied adipose-derived products for wound repair. It is a heterogeneous cell population derived from adipose tissue, and the cellular heterogeneity allows SVF to participate in wound repair through several coordinated mechanisms: secretion of proangiogenic factors, modulation of inflammatory cells, support of endothelial network formation, recruitment of host repair cells, and enhancement of granulation tissue formation^[78]. SVF is an autologous, multifunctional strategy for wound healing, especially because it combines cellular trophic activity with vascular and immunomodulatory functions. ADSCs contribute to wound repair mainly through paracrine effects rather than direct tissue replacement. They secrete growth factors, cytokines, extracellular vesicles, and matrix-remodeling mediators. These signals can promote endothelial cell migration, keratinocyte proliferation, fibroblast activity, collagen deposition, and macrophage polarization toward a pro-repair phenotype. ADSCs are therefore often regarded as a central biological component underlying the regenerative effects of SVF, nanofat, and other adipose-derived products^[79].

Nanofat is suitable for cutaneous repair because it is mechanically emulsified into adipose fragments that can be injected into superficial dermal or subdermal planes. It has limited volumizing capacity but retains stromal cells, vascular-associated cells, and ECM microfragments^[80]. Nanofat has been investigated for wound healing and skin rejuvenation. Its main functions in wound repair are to enhance angiogenesis and improve dermal matrix remodeling^[81].

SVF-gel is particularly relevant to chronic wounds because it combines stromal vascular components with concentrated adipose ECM^[82]. Compared with isolated SVF cell suspension, SVF-gel may provide better local retention, a more favorable microenvironment for stromal cells, and longer-lasting paracrine activity. Clinical and mechanistic studies have reported that SVF-gel can promote chronic wound healing^[83], restore more normal cutaneous structures, enhance collagen deposition, reduce inflammation and fibrosis, promote angiogenesis, and support peripheral nerve recovery^[84].

CEFFE represents a different wound-healing strategy. Unlike SVF and ADSCs, CEFFE is cell-free; unlike adECM or ADF, it is not primarily a structural scaffold. Instead, it is a soluble adipose-derived extract enriched in bioactive factors. In wound repair, CEFFE acts as a paracrine mimetic product that promotes cell proliferation, endothelial activity, angiogenesis, and matrix remodeling. As an adipose-derived cell-free therapy, CEFFE can accelerate angiogenesis, epithelial ingrowth, and wound closure in experimental models^[85].

adECM, ADF, and AAF are more scaffold-oriented wound-healing products. adECM retains adipose-tissue-specific ECM cues after decellularization and can support host-cell infiltration, angiogenesis, and soft-tissue remodeling. ADF and AAF extend this concept into film-like materials that can be applied as wound covering membranes or regenerative interfaces. ADF has been described as an adipose-derived matrix membrane with mechanical strength and biological activity, while AAF has been developed as a flexible acellular adipose-derived film for skin soft-tissue regeneration^[86].

From a clinical selection perspective, adipose-derived products for wound repair should be chosen according to whether the wound primarily requires cellular immune modulation, sustained angiogenic stimulation, structural coverage, or scaffold-guided tissue remodeling. SVF and ADSCs are particularly relevant when impaired vascularization and chronic inflammation are dominant pathological features, whereas nanofat and SVF-gel may be more suitable for superficial or irregular wound beds that require injectable delivery and local retention. CEFFE represents a cell-free trophic-factor strategy and may be advantageous when lower cellular risk or repeated administration is preferred. In contrast, adECM, ADF, and AAF are better positioned as scaffold- or film-based materials for wound coverage and guided host-cell infiltration. Therefore, wound healing applications should match the product type to the dominant biological deficit of the wound, such as ischemia, inflammation, matrix loss, poor epithelialization, or lack of mechanical coverage.

In aesthetic dermatology, adipose-derived products are used for dermal thickening, collagen remodeling, vascular regeneration, improvement of skin texture, correction of fine wrinkles, and reversal of photoaging-associated matrix degeneration.

Nanofat is one of the most representative adipose-derived products for skin rejuvenation. Because it is injectable through small-gauge needles and contains stromal cells and matrix microfragments, nanofat is often used for fine wrinkles, acne scars, periorbital skin thinning, and general skin-quality improvement. Its effect is not primarily based on long-term fat survival, but rather on regenerative signaling, dermal remodeling, neovascularization, and stimulation of local repair pathways. Nanofat is a minimally invasive regenerative tool in aesthetic and reconstructive surgery, although standardized preparation protocols and stronger long-term clinical evidence are still needed^[87].

ACF is especially relevant to dermal filling and rejuvenation. It is prepared from adipose tissue by mechanical processing and is enriched in collagen ECM components. ACF contains high levels of collagen I, collagen IV, and laminin, with low or absent viable cellular content. Functionally, ACF acts as a collagen-rich, adipose-derived matrix scaffold that can improve dermal thickness, stimulate collagen synthesis, and serve as an autologous filler for fine wrinkles, particularly in superficial areas such as infraorbital rhytides^[88].

CEFFE can also be classified under skin rejuvenation because it provides soluble regenerative signals without live cells or structural matrix. In experimental models, CEFFE increased dermal thickness, capillary density, proliferating cells, and collagen I/III expression^[43]. This suggests that CEFFE may improve aging skin by promoting angiogenesis, keratinocyte or fibroblast proliferation, and dermal ECM production^[89].

SVF-gel occupies an intermediate position between regenerative skin therapy and soft-tissue filling. It contains concentrated stromal vascular components and adipose ECM, so it can provide mild volumetric correction while also improving dermal trophic support^[82]. It is therefore suitable for facial soft tissue atrophy, periorbital hollowing, nasolabial folds, post-traumatic contour defects, and areas where both regeneration and limited filling are desired^[32].

For skin rejuvenation and dermal regeneration, the key therapeutic requirement is usually not bulk volume replacement but improvement of dermal quality, vascularity, collagen organization, and ECM remodeling. Nanofat is appropriate for superficial regenerative injection because it contains stromal cells and matrix microfragments but has limited volumizing capacity. ACF is more matrix-dominant and may be preferable for fine rhytides, infraorbital lines, and dermal thinning where collagen-rich support is needed. CEFFE provides soluble regenerative signals without viable cells or structural graft material, whereas SVF-gel provides both stromal vascular components and an ECM niche. Therefore, product selection in aesthetic dermatology should distinguish between dermal biostimulation, collagen support, paracrine stimulation, and regenerative filling.

Scarred and fibrotic tissues are characterized by abnormal collagen deposition, reduced vascularity, chronic inflammation, stiffness, and impaired ECM organization. In this field, adipose-derived products function mainly through anti-inflammatory, proangiogenic, antifibrotic, and matrix-remodeling mechanisms^[87].

Nanofat is widely used for scar remodeling because it can be injected into superficial fibrotic tissue and contains stromal cells and ECM fragments. Systematic reviews indicate that nanofat has been primarily investigated in the context of skin scar repair, including improvement of scar quality, texture, pliability, and dermal structure. Experiments also support the concept that nanofat can enhance tissue vascularization and improve healing in radiation-injured skin^[90].

SVF and ADSCs contribute to scar remodeling by regulating inflammation, suppressing excessive fibroblast activation, and altering collagen remodeling. ADSC-derived paracrine factors may reduce profibrotic signaling, enhance local vascularity, and promote a more regenerative immune microenvironment. SVF may provide a broader stromal and vascular cell mixture than isolated ADSCs, which may be advantageous in scarred tissue where vascular deficiency and chronic inflammation coexist^[87].

SVF-gel is useful for scars that combine tissue depression, fibrosis, and poor vascularity. It can provide both a regenerative ECM niche and stromal vascular components^[91]. Studies of SVF-gel in chronic wounds reported reduced fibrosis and inflammation, improved collagen deposition, angiogenesis, and peripheral nerve recovery, suggesting that its functions extend beyond volume correction to active scar remodeling^[92].

ACF can be used for superficial scars and fine scar-like wrinkles because it provides a collagen-rich autologous matrix. Its main contribution is dermal ECM support and collagen remodeling rather than cellular immunomodulation. This makes ACF conceptually useful for atrophic scars, fine rhytides, and dermal thinning, especially when a more matrix-dominant product is preferred^[93].

In scarred, fibrotic, or radiation-damaged tissues, the therapeutic goal differs from that of simple tissue filling. These tissues require restoration of vascularity, reduction of chronic inflammation, modulation of fibroblast activity, softening of excessive collagen deposition, and reconstruction of a more organized ECM. Nanofat and SVF-gel are suitable for scar remodeling because they can be injected into fibrotic tissue planes and provide stromal cells, matrix fragments, and paracrine signals. SVF and ADSCs may be more appropriate when immune modulation and vascular regeneration are the primary objectives, whereas ACF may be selected when the dominant problem is superficial dermal atrophy or collagen deficiency. A function-based strategy should therefore prioritize products with anti-inflammatory, proangiogenic, antifibrotic, and matrix-remodeling capacities.

In soft tissue reconstruction, adipose-derived products are used to restore volume, improve graft survival, enhance vascular ingrowth, reduce resorption, and reconstruct adipose-like tissue. The most relevant products are SVF, ADSCs, SVF-gel, AMC, ACF, adECM, ADF, and AAF, but their roles differ substantially^[94].

SVF- and ADSC-assisted fat grafting aim to improve fat graft survival by accelerating early revascularization and reducing ischemic injury after transplantation. SVF and ADSCs provide endothelial support, perivascular cells, trophic factors, and immunomodulatory signals. SVF- and ADSC-enriched fat grafting is a good strategy used in reconstructive and aesthetic plastic surgery to improve graft retention and regenerative outcomes, although long-term efficacy, mechanistic clarity, and standardization remain variable^[2,95].

SVF-gel is useful when conventional fat grafting is limited by oil cyst formation, unpredictable retention, or poor contour control. Because it contains concentrated ECM and stromal vascular components with less free lipid, SVF-gel can act as a regenerative filler for facial atrophy, contour depression, scar-related soft-tissue defects, and potentially for breast or reconstructive applications^[50].

AMC is better suited to structurally demanding regions. Because AMC contains a higher proportion of type I collagen and has greater stiffness than Coleman fat, it can be used for clinical filling of areas requiring rigid support, such as the nasal base and chin. In functional terms, AMC should be classified as a high-rigidity, collagen-rich adipose matrix filler rather than primarily as a cellular regenerative product^[16].

adECM is important for scaffold-based soft tissue reconstruction. These materials remove immunogenic cellular components while preserving adipose-specific ECM cues. They can support host-cell infiltration, vascularization, adipogenesis, and long-term tissue remodeling. adECM has undergone preclinical characterization and pilot clinical testing, and human DAM is a promising off-the-shelf scaffold for soft-tissue regeneration^[10].

ADF may expand soft-tissue reconstruction from injectable grafting toward sheet-like regenerative interfaces. ADF has been proposed as an adipose-derived ECM film with mechanical strength, biological activity, and potential for personalized matrix storage (“ECM” bank)^[10].

In soft-tissue reconstruction, different adipose-derived derivatives should be selected according to whether the clinical objective is durable volume restoration, rigid structural support, improvement of fat graft survival, or scaffold-guided adipose regeneration. SVF- or ADSC-assisted fat grafting is mainly intended to improve graft vascularization and reduce ischemia-related resorption, whereas SVF-gel provides a matrix-rich injectable material with better local retention and a lower lipid burden than conventional fat. AMC is more suitable for structurally demanding regions because its collagen-rich and high-stiffness properties provide mechanical support. adECM and ADF should be considered scaffold-based or interface-based materials that rely on host-cell infiltration, vascularization, and gradual remodeling rather than immediate volumetric correction.

Tissue expansion requires adequate vascularity, dermal thickness, epidermal proliferation, ECM remodeling, and resistance to ischemia. Similarly, flap survival and ischemic tissue repair depend on effective neovascularization and tissue remodeling. Adipose-derived products such as CEFFE, SVF, ADSCs, and AAF play key regenerative roles.

CEFFE is a cell-free, soluble adipose-derived product that improves expanded skin quality by promoting angiogenesis and keratinocyte proliferation. In rat tissue expansion models, CEFFE increased the expression of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), collagen types I and III, and enhanced keratinocyte proliferation in vitro. Its proangiogenic and proliferative activity also makes it suitable for ischemic soft tissue, chronic wounds, and biomaterial-assisted vascularization, thereby providing regenerative support without cell transplantation^[96].

AAF is a film-like AAM designed as a flexible bioactive interface for skin soft tissue expansion. It can enhance keratinocyte, fibroblast, and endothelial cell activity, promote angiogenesis, increase expanded skin thickness, and induce subcutaneous adipose regeneration. AAF may also provide a structural template that supports vascular ingrowth in ischemic tissues.

SVF contains endothelial progenitor-like cells, pericytes, ADSCs, and vascular-supporting stromal cells, which contribute directly to vascular regeneration. Transplanted SVF can form mature vascular networks, including arteries, capillaries, veins, and lymphatics. In human-in-mouse models, SVF-derived endothelial cells form hybrid vessels stabilized by perivascular cells, supporting both tissue expansion and flap perfusion^[97]. ADSCs promote vascular regeneration primarily through paracrine signaling. They secrete VEGF, HGF, angiopoietin-related signals, extracellular vesicles, and anti-apoptotic factors, which enhance endothelial survival, capillary sprouting, and tissue perfusion. ADSCs are a major source of trophic and proangiogenic factors, addressing vascular insufficiency and impaired tissue remodeling in expanded or ischemic skin^[98].

For tissue expansion and ischemic tissue repair, the most relevant adipose-derived products are those that enhance vascularization, improve dermal and subcutaneous tissue quality, and reduce ischemia-related complications. CEFFE may be useful as a cell-free proangiogenic and proliferative stimulus. SVF and ADSCs may provide stronger cellular support for neovascularization and inflammatory regulation, but their efficacy depends on cell viability, dose, delivery route, and the ischemic microenvironment. AAF is attractive because its film-like morphology allows it to function as a bioactive interface between the expander, skin flap, wound surface, and surrounding tissue.

In musculoskeletal applications, adipose-derived products are used mainly for anti-inflammatory regulation, pain reduction, joint microenvironment modulation, chondroprotection, matrix protection, and tendon repair^[99].

SVF and ADSCs are widely studied for knee osteoarthritis. Their expected benefit is not simply direct cartilage replacement, but modulation of synovial inflammation, suppression of catabolic mediators, secretion of trophic factors, and improvement of joint homeostasis. Clinical studies with more than 2 years of follow-up have generally reported improvement in pain relief and joint function improvement after SVF treatment, with minimal adverse reactions, although protocols and outcome measures remain heterogeneous. However, the clinical evidence remains mixed, and robust standardization is still lacking. SVF preparations differ according to enzymatic or mechanical processing, cell composition, dose, donor variability, and injection protocols. Therefore, SVF and ADSCs should be described as promising but not yet fully standardized therapies for osteoarthritis^[100].

CEFFE has emerging relevance in musculoskeletal regeneration as a cell-free alternative to adipose-derived cell therapy. CEFFE is a non-cellular adipose-derived therapeutic approach alongside extracellular vesicles. Because CEFFE contains soluble trophic factors, it may theoretically regulate inflammation, oxidative stress, and matrix metabolism, but its orthopedic evidence base remains less mature than that of SVF or ADSCs. CEFFE-loaded biomaterials may be especially useful in tendon repair. A long-acting microneedle patch loaded with adipose-derived bioactive components has been developed for tendinopathy, suggesting that cell-free adipose extracts may be delivered through sustained-release platforms to reduce inflammation, protect matrix integrity, and support tissue recovery^[101].

adECM functions as a versatile and bioactive scaffold, preserving native matrix components and three-dimensional architecture that support cell adhesion, migration, and differentiation. In volumetric muscle loss (VML) models, perfusable adECM scaffolds co-recellularized with ADSCs and L6 myoblasts enable uniform cell distribution, enhance myogenesis and angiogenesis, and improve functional muscle recovery, while revealing ADSC subpopulations with enhanced regenerative potential. Complementarily, adECM combined with STIM1-overexpressing ADSCs and sustained IGF-2 delivery directs myogenic differentiation, suppresses fibrosis, and promotes M2 macrophage polarization, thereby optimizing the immune microenvironment for muscle repair. Together, these studies demonstrate that adECM serves as a multifunctional platform that synergizes with therapeutic cells and growth factors to promote oriented muscle fiber formation, vascularization, immune modulation, and functional restoration after severe muscle injury, highlighting its translational potential in regenerative medicine^[9,60].

In musculoskeletal applications, adipose-derived products should be interpreted primarily as modulators of the local inflammatory and reparative microenvironment rather than as direct replacements for cartilage, tendon, or muscle tissue. SVF and ADSCs are the most extensively studied products for osteoarthritis because they can modulate synovial inflammation, secrete trophic factors, and influence immune and stromal cell behavior. CEFFE represents an emerging cell-free alternative that may provide anti-inflammatory and trophic effects with fewer concerns related to viable cell transplantation, although its musculoskeletal evidence remains less mature. adECM-based scaffolds are more relevant for tissue engineering applications that require structural guidance, cell attachment, and sustained remodeling.