Definition and purpose of microfragmentation
Microfragmentation of adipose tissue refers to the mechanical harvesting of adipose clusters through cannulas with small side-port holes, generating a highly fluid fat graft composed of small adipose aggregates without the need for subsequent aggressive processing. In the SEFFI (Superficial Enhanced Fluid Fat Injection) and micro-SEFFI approaches, the adipose tissue is dissociated into small clusters directly during the harvesting step by using microcannulas (for example, 0.8 mm and 1 mm side-port holes), thereby obtaining micro-fragmented adipose tissue suitable for injection and regenerative purposes. This tissue naturally contains stromal vascular fraction (SVF) cells and adipose-derived stromal/stem cells (ASCs), which are considered central to its regenerative potential.
The primary purpose of microfragmentation in regenerative therapy is to obtain an autologous adipose graft that is rich in stromal vascular fraction and mesenchymal stromal cells, while maintaining high cell viability and minimizing manipulation. Regenerative therapy based on the injection of micro-fragmented adipose tissue has been proposed as a promising treatment for degenerative diseases or disorders that are not adequately controlled with conventional care, and it is also used in antiaging applications. By exploiting the biological properties of SVF and ASCs, microfragmented adipose tissue can be used as a regenerative filler and as a biologically active graft in musculoskeletal and soft-tissue indications.
In orthobiology, microfragmented adipose tissue is used as an autologous regenerative therapy (ART) to stimulate repair or regeneration of injured tissues. Autologous regenerative therapy utilizes the patient’s own mesenchymal stromal cells in a single medical procedure, with the mesenchymal cells differentiating according to signals from the surrounding environment and local growth factors. Intra-articular injection of autologous micro-fragmented adipose tissue has been applied to osteoarthritis of the hip and knee, with the rationale that adipose-derived cells, cytokines, and growth factors may support cartilage and joint tissue homeostasis.
In aesthetic and dermatologic fields, microfragmented adipose tissue is used as a regenerative filler to provide both volumization and skin quality improvement. The micro-SEFFI technique, for example, is designed to harvest highly fluid microfat suitable for facial rejuvenation, with tissue that contains viable adipocytes and SVF/ASCs. The combination of mechanical microfragmentation and minimal manipulation aims to deliver a tissue that can be injected through fine cannulas into superficial planes, supporting tissue regeneration and remodeling in addition to simple volume restoration.
Preserving stromal niche and ECM
Microfragmentation techniques are conceived to preserve the stromal niche and elements of the extracellular matrix (ECM) that support stromal and vascular cells. Adipose tissue contains a complex stromal vascular fraction composed of adipocyte progenitors, pericytes, endothelial progenitor cells, and transit-amplifying cells embedded within an ECM scaffold. Mechanical harvesting with microcannulas produces small adipose clusters in which cells remain partially entrapped in their native ECM, and viable cells are released from the tissue during and after the procedure. The presence of viable and metabolically active cells within the harvested tissue at 72 hours indicates that both released cells and cells retained in the ECM remain functional after microfragmentation.
The ECM plays a structural and regulatory role for mesenchymal stromal cells, influencing their proliferation, migration, and differentiation. Studies on mesenchymal stem cells have shown that decellularized matrices derived from these cells can modulate their self-renewal and lineage commitment, underscoring the importance of the microenvironment. In the context of microfragmented adipose tissue, maintaining ECM fragments and cell aggregates within the graft may help preserve a supportive microenvironment for ASCs and pericytes. Analytical characterization of micro-SEFFI tissue using Celector technology has demonstrated the presence of large cell aggregates composed of adipocytes and ECM, as well as ECM fragments and single cells liberated during aspiration, confirming that the harvested product retains structural stromal components.
Stromal cells and pericytes within the SVF secrete a wide variety of factors with antifibrotic, anti-apoptotic, immunomodulatory, and neo-vascularization properties. These paracrine activities are thought to contribute to clinical effects observed after adipose tissue grafting, such as improved skin trophism, accelerated closure of complex wounds or ulcers, and enhancement of skin appearance after radiotherapy. By preserving the stromal niche and ECM fragments, microfragmentation techniques aim to maintain not only the cells themselves but also their capacity to interact with and remodel the surrounding matrix after transplantation.
The SEFFI and micro-SEFFI systems are explicitly designed to obtain re-injectable tissue with minimal manipulation, thereby limiting disruption of the stromal niche. In these systems, the selection of cluster size is achieved during harvesting through the use of cannulas with defined side-port diameters, avoiding subsequent mechanical shredding or emulsification steps. This approach reduces additional mechanical stress on cells and ECM, which has been associated with decreased stemness and cell viability in more aggressive processing methods. The resulting microfragmented tissue thus contains viable stromal cells within a partially preserved ECM scaffold, which may be advantageous for regenerative applications.
Processing of adipose tissue
Processing of adipose tissue for microfragmentation-based regenerative therapy begins with harvesting using dedicated microcannulas. In the SEFFI technique, a guided device is used to standardize cannula depth at approximately 15 mm, targeting the superficial adipose tissue (SAT) adjacent to the dermis, which has been reported to contain higher numbers of mesenchymal and vascular stem cells. The device includes both a harvesting cannula and a guide, allowing tunneling in a reproducible subcutaneous plane and collecting micro-fragmented adipose tissue in a closed, disposable system.
In comparative studies, adipose tissue has been harvested using cannulas with 0.8 mm and 1 mm side-port holes, as well as with a standard liposuction cannula followed by enzymatic digestion. The microcannulas with small side ports (0.8 and 1 mm) are used to directly select the size of adipose clusters during the harvesting procedure, so that no substantial post-harvest manipulation is required to thin the tissue. Lipoaspirate obtained with these microcannulas has been shown to contain vital and metabolically active cells, with increased cell viability observed after 72 hours of culture, indicating that both cells released by the mechanical action and those entrapped in the ECM remain functional.
In contrast, enzymatic processing typically involves digestion of lipoaspirate with collagenase at 37 °C, followed by filtration and centrifugation to isolate the SVF pellet. This method disrupts the ECM and cell–cell binding, yielding a cell suspension enriched in SVF cells that can be plated and expanded. While enzymatic digestion is particularly indicated for SVF isolation, it is subject to regulatory constraints, especially in certain jurisdictions, and requires more complex laboratory handling. Microfragmentation techniques, by contrast, aim to remain within the framework of minimal manipulation by avoiding enzymatic steps and extensive ex vivo processing.
For micro-SEFFI used in facial aging treatment, harvested tissue is characterized by high fluidity and small cluster size, enabling injection into superficial and delicate facial areas. Microscopy and Celector-based fractionation have shown that micro-SEFFI samples contain small adipose aggregates, ECM fragments, single cells, and fat droplets, with a defined elution profile that reflects tissue composition. From these samples, ASCs can be isolated and expanded in vitro, demonstrating classical mesenchymal morphology, colony-forming capacity, and differentiation toward adipogenic, osteogenic, and chondrogenic lineages. These findings support the concept that microfragmented adipose tissue, obtained through controlled mechanical processing, provides a viable and regenerative cell–matrix product suitable for clinical use.
Advantages vs enzymatic digestion
Microfragmentation techniques offer several practical advantages compared with enzymatic digestion of adipose tissue. A key feature is that microfragmentation can yield a tissue with a good amount of viable cells through minimal manipulation, without the need for collagenase or other enzymes. In a comparative study, adipose tissue harvested with microcannulas (0.8 and 1 mm side-port holes) showed cell viability comparable to tissue processed by standard liposuction followed by enzymatic digestion, with similar absorbance values at baseline and after 72 hours, indicating that both approaches can harvest vital tissue.
Enzymatic digestion is effective in isolating SVF because it disrupts the ECM and the binding of adipocytes and other cells, but it is restricted by regulatory issues related to enzymatic procedures, particularly in some regulatory environments. Microfragmentation with guided microcannulas avoids enzymatic steps and is performed as a closed, disposable, all-in-one procedure, which can be completed in a relatively short time frame in a clinical setting. This simplifies logistics, reduces the need for specialized laboratory infrastructure, and aligns with the concept of point-of-care autologous regenerative therapy.
Another advantage of microfragmentation is the preservation of tissue architecture, including ECM fragments and cell aggregates, which are largely lost during enzymatic digestion. Celector-based analysis of micro-SEFFI samples has demonstrated the presence of large adipocyte–ECM aggregates and ECM fragments, along with single cells and fat droplets, providing a complex tissue composition that may support stromal cell function after transplantation. In addition, studies have indicated that additional mechanical manipulation of adipose tissue can reduce stemness and cell viability, whereas tissue harvested with SEFFI without substantial manipulation shows higher viability and growth rate compared with techniques involving more intensive mechanical processing.
From a regulatory and clinical workflow perspective, microfragmentation is framed as a minimal manipulation technique that uses the patient’s own tissue in a single procedure. The SEFFI and micro-SEFFI systems are designed to harvest re-injectable tissue directly, without the need for additional devices for graft processing. This contrasts with enzymatic digestion protocols, which require incubation, washing, and cell counting steps before reinjection. While enzymatic digestion remains a reference method for isolating SVF cells for research and some clinical applications, microfragmentation provides a practical alternative that combines viable stromal cells with preserved ECM in a format suitable for immediate clinical use.
Clinical applications in orthobiology
In orthobiology, microfragmented adipose tissue has been applied as an autologous regenerative therapy for osteoarthritis (OA) of large joints. Osteoarthritis is characterized by degeneration of articular cartilage, joint pain, and functional impairment, with limited intrinsic healing capacity due to poor vascularization and restricted access to progenitor cells. Autologous regenerative therapy aims to regenerate or stimulate repair of injured tissues using the patient’s own mesenchymal stromal cells in a single procedure. In this context, adipose-derived stem cells located in the SVF of adipose tissue are frequently used in orthopedics because of their capacity to support regeneration of cartilage, tendons, and bone.
A clinical series has described the management of hip and knee OA using intra-articular injection of autologous fat micrograft obtained with the Sefficare device, a SEFFI-based system. Patients with initial-stage degenerative OA of the hip or knee underwent a single-session procedure in which donor adipose tissue was harvested, SVF-containing microfragmented fat was isolated, and the resulting micrograft was injected intra-articularly. The entire procedure required approximately 60–70 minutes. Postoperative assessments at 3, 6, and 12 months included range of motion (ROM), pain evaluation using a visual analogue scale (VAS), and functional questionnaires.
In this cohort, an average increase of about 10 degrees in joint ROM was observed three months after treatment, accompanied by reduced stiffness as reported by patients. Pain reduction on the VAS began around three months and reached its maximum at approximately six months for the knee and between six and twelve months for the hip. Clinical improvement in terms of pain reduction and joint performance appeared more pronounced in younger patients with lower OA grade, although even patients with more severe OA reported pain reduction and satisfactory outcomes. At one year, a high proportion of patients reported satisfaction with the procedure, with improvement in pain and quality of life.
Beyond large-joint OA, microfragmented adipose tissue has been proposed as a promising source for regenerative treatments in other musculoskeletal and soft-tissue conditions. Regenerative therapy based on microfragmented adipose tissue has been described as a potential option for degenerative diseases not adequately managed by conventional care, and it has also been explored in gynecology, where injection of microfragmented adipose tissue has been reported as a promising therapy in genitourinary syndrome of menopause. In aesthetic and reconstructive settings, adipose tissue implantation has been used to improve skin trophism, accelerate closure of complex wounds or ulcers, and enhance skin appearance after radiotherapy, effects that are attributed in part to the antifibrotic, immunomodulatory, and angiogenic properties of ASCs and SVF cells.
Scientific background and performance
The scientific rationale for microfragmentation-based regenerative therapy is grounded in the biology of adipose-derived mesenchymal stromal cells and the stromal vascular fraction. Human adipose tissue has been identified as a source of multipotent mesenchymal stromal cells similar to those found in bone marrow, with the ability to differentiate into adipogenic, osteogenic, chondrogenic, myogenic, hepatogenic, and endothelial lineages in vitro and in vivo. ASCs and SVF cells also exhibit antifibrotic, immunomodulatory, and pro-angiogenic properties, which are believed to contribute to tissue repair and regeneration in clinical applications.
Experimental work has evaluated the performance of adipose tissue harvested with microfragmentation techniques. In a study comparing harvesting and processing techniques, lipoaspirate obtained with 0.8 mm and 1 mm side-port microcannulas showed high cell viability immediately after plating and after 72 hours, with an increase in viability over time, indicating the presence of viable and proliferative cells both within the tissue and released by the mechanical procedure. The average absorbance values for these mechanically harvested tissues were comparable to those of SVF cells derived from enzymatically digested lipoaspirate, supporting the conclusion that minimally manipulated microfragmented adipose tissue can yield a viable cell population suitable for regenerative use.
Additional characterization of micro-SEFFI-derived tissue has confirmed that ASCs can be isolated from microfragmented lipoaspirate harvested with cannulas bearing 0.3, 0.5, or 0.8 mm side-port holes. These ASCs display classical mesenchymal morphology, form colony-forming units, and demonstrate differentiation toward adipogenic, osteogenic, and chondrogenic lineages, confirming their stemness potential. Despite the small cluster size and relatively low cellularity of micro-SEFFI tissue, stem cells can be isolated and expanded, which partially explains the regenerative potential observed clinically when this tissue is re-injected.
Clinically, intra-articular injection of autologous microfragmented adipose tissue in hip and knee OA has been associated with improvements in pain, ROM, and patient-reported quality of life over a follow-up period of up to twelve months. The procedure is described as minimally invasive, with an uneventful donor-site course apart from minimal discomfort, and can be completed in approximately one hour. While the reported cohort lacks a control group and includes mainly patients with mild to moderate OA, the observed clinical benefits and high patient satisfaction support further investigation of microfragmented adipose tissue as a component of orthobiologic treatment strategies. Ongoing research on mesenchymal stem cell therapies in osteoarthritis and other conditions provides a broader scientific context for these findings.
Sources (Bibliography)
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