اثر ترکیبی بخش استرومال عروقی (SVF) و فیبرین غنی از پلاکت (PRF) در مدیریت آرتروز زانو و لگن: مطالعه پیگیری دو ساله

مقدمه: آرتروز یک بیماری مزمن و شایع مفصلی است. در سال‌های اخیر، پزشکی بازساختی با استفاده از ترکیب بخش استرومال عروقی (SVF) مشتق از چربی و فیبرین غنی از پلاکت (PRF) توجه زیادی را به خود جلب کرده است.
روش‌ها: این مطالعه یک بررسی گذشته‌نگر بر روی 104 بیمار مبتلا به آرتروز زانو یا لگن بود که تحت تزریق داخل‌مفصلی SVF و PRF قرار گرفتند. نمرات WOMAC در شروع مطالعه، 6 ماه و 2 سال بعد، و همچنین تصاویر رادیوگرافی پیش و 6 ماه پس از درمان، تحلیل شد.
نتایج: بهبود آماری بسیار معنی‌داری در نمرات کل WOMAC (84.5٪ کاهش، 0.0001=p) و افزایش معنی‌دار فضای مفصلی در هر دو گروه زانو (2 میلی‌متر) و لگن (1.6 میلی‌متر) مشاهده شد.
نتیجه‌گیری: ترکیب SVF و PRF روشی مؤثر و کم‌تهاجم در درمان آرتروز زانو و لگن است و می‌تواند به عنوان جایگزینی برای جراحی تعویض مفصل در نظر گرفته شود.

Efficacy of Stromal Vascular Fraction (SVF) Combined with Platelet-Rich Fibrin (PRF) for Osteoarthritis Management in Knee and Hip Joints: A Retrospective 2-Year Follow-Up Study

Author: Torbjörn Ogéus DC, PgD, MSc

Stockholms led- & smärtklinik, 11424, Stockholm, Sweden

Abstract

Introduction: Regenerative medicine has emerged as a promising frontier in the management of musculoskeletal disorders, including osteoarthritis (OA). Among these, stromal vascular fraction (SVF) therapy combined with platelet-rich fibrin (PRF) has garnered significant attention for its potential to mitigate OA progression and promote joint regeneration.

Methods: This retrospective database cohort study included 104 patients who underwent SVF and PRF treatment for hip or knee OA between January 2020 and January 2022. Data analyzed included 2-year follow-up Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and radiographic evaluations taken before and 6 months post-treatment.

Results: Statistically significant positive changes in WOMAC scores ($p=0.0001$) were observed for both hip and knee OA. Radiographic analysis demonstrated a mean joint space increase of 2 mm for knees and 1.6 mm for hips ($p=0.0001$).

Conclusion: SVF combined with PRF is a highly effective, minimally invasive treatment that significantly reduces long-term clinical symptoms and increases radiographic joint space over a 2-year period.

Keywords: Stem cell, SVF, PRF, Regenerative medicine, Knee, Hip, Osteoarthritis, Radiographic WOMAC.

Introduction

Osteoarthritis (OA) is a highly prevalent chronic joint disorder characterized by the progressive degeneration of articular cartilage, subchondral bone alterations, and chronic synovial inflammation. Driven by a globally aging population and rising obesity rates, the socio-economic and clinical burden of OA continues to escalate rapidly. Conventional management approaches—such as nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and intra-articular corticosteroid injections—offer temporary symptomatic relief but fundamentally fail to halt disease progression or facilitate tissue repair. Consequently, when conservative strategies fail, total joint replacement surgery becomes the ultimate, highly invasive alternative. This underscores a critical need for innovative therapeutic modalities capable of targeting the underlying pathophysiological mechanisms of joint degeneration.

In recent years, regenerative medicine has introduced promising cell-based strategies. Among these, the combination of stromal vascular fraction (SVF) and platelet-rich fibrin (PRF) represents a compelling biological therapeutic paradigm. SVF is a heterogeneous cell population isolated from autologous adipose tissue containing mesenchymal stem cells (MSCs), endothelial progenitor cells, T-regulatory cells, and an array of essential growth factors. PRF is a autologous concentrate of platelets and leukocytes obtained through blood centrifugation, acting as a natural fibrin matrix that continuously releases crucial bioactive molecules, including transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF).

When combined, SVF and PRF exert a powerful synergistic effect, blending the multilineage differentiation potential of stem cells with the localized, sustained release of regenerative growth factors. Although preliminary short-term cartilage regrowth has been demonstrated via arthroscopic imagery following isolated MSC therapies, long-term clinical evidence evaluating the combination of SVF and PRF remains sparse. This retrospective study addresses this gap by presenting 2-year clinical and radiographic follow-up data from 104 patients with knee and hip OA.

Materials and Methods

Preparation of PRF, ALB-PRF, and SVF

All patients followed a standardized protocol at the clinic. For the platelet concentrations, 40 ml of peripheral blood was extracted from the patient using four 10 ml plastic, round-bottom vacuum tubes (Liquid PRF tubes) and processed using a horizontal swing-out bucket rotors centrifuge system (Bio-PRF, USA). Two distinct PRF protocols were utilized based on international guidelines published by Miron et al. (2019) :

  1. Concentrated-PRF (C-PRF): Centrifuged at 2000×g for 8 minutes to extract a 4 ml injectable active layer.

  2. Albumin Gel-PRF (ALB-PRF): 5 ml of platelet-poor plasma (PPP) was separated via horizontal centrifugation at 2000×g for 8 minutes. The isolated albumin layer was heated at 75°C for 10 minutes to form a highly biocompatible albumin gel, extending its joint resorption timeline from 2 weeks to over 4 months. The heated gel was then cooled to room temperature and mixed back with liquid C-PRF to synthesize the final long-acting ALB-PRF compound.

The SVF cell population was isolated utilizing the automated MyStem™ system protocol (MyStem evo Bi-Medica, Treviolo, Italy). An 80 ml volume of autologous adipose tissue was harvested via abdominal liposuction. The lipoaspirate underwent strict filtration and washing cycles to completely remove residual fluids and free oils, yielding a concentrated 10 ml SVF cell suspension ready for intra-articular delivery.

Administration Protocol

The therapeutic series consisted of precisely timed intra-articular injections into the affected joints under strict ultrasound guidance to guarantee flawless intra-capsular delivery.

  • Week 1: Patients received one intra-articular C-PRF injection, followed two days later by the primary autologous SVF injection.

  • Week 2: Two follow-up C-PRF injections were administered two days apart to act as biological primers.

  • Rehabilitation: The treatment wrapped up with a final intra-articular ALB-PRF gel injection. Following the SVF injection, patients were placed on a mandatory 5-week non-weight-bearing restriction utilizing crutches. Upon completion of this phase, a progressive rehabilitation program was initiated, consisting of 15 minutes of daily stationary bicycling and low-resistance strength training.

Study Design and Subjects

This retrospective database cohort study reviewed patient records from January 2020 to January 2022. According to the Ethics Commission of Stockholm (Sweden), retrospective studies utilizing fully anonymized data do not require formal ethical approval or specific informed patient consent, though the study strictly adhered to the 1964 Declaration of Helsinki.

A total of 123 patients consented to data tracking. Patients were formally included if they completed the full clinical protocol and possessed complete datasets. Patients were excluded if their medical records lacked key timeline entries or if they breached the 5-week non-weight-bearing protocol. Ultimately, 104 patients met the criteria (50 female, 54 male), divided into 53 knee OA patients and 51 hip OA patients.

Clinical Outcome Instruments & Radiographic Database

Clinical evaluation relied on the self-administered 24-item WOMAC scale across three major domains: Pain (5 items; max score 20), Stiffness (2 items; max score 8), and Physical Function (17 items; max score 68). Lower total index and subscale scores indicate improved clinical outcomes and reduced disability. Questionnaires were completed at baseline, 6 months, and 2 years post-treatment. Concurrently, digital weight-bearing radiographic imaging was conducted at baseline and 6 months to track joint space width variations in millimeters (mm).

Statistical Analysis

Continuous baseline and follow-up data were characterized using Mean $\pm$ Standard Deviation (SD). Normal distribution curves were verified using independent t-tests and analysis of variance (ANOVA) protocols via Prism 10 for Windows (Microsoft, USA), setting statistical significance strictly at $p \le 0.05$.

Results

Demographics

The mean overall age of the cohort was $62.55 \pm 3.93$ years. No statistically significant baseline differences were detected between the knee and hip sub-cohorts regarding age ($p=0.17$) or gender distribution ($p=0.53$), confirming clean comparative groups.

Parameter Knee OA (n=53) Hip OA (n=51) p-value
Age (years) $63.9 \pm 5.68$ $61.2 \pm 2.19$ $p=0.17$
Gender: Male (%) 27 (50.9%) 26 (50.9%) $p=0.53$
Gender: Female (%) 26 (49.1%) 25 (49.0%) —

Table 1: Demographic profile of the baseline sample cohort.

WOMAC Clinical Data Outcomes

The longitudinal analysis revealed exceptionally positive clinical trajectories across both groups over the 2-year tracking window ($p=0.0001$).

  • Knee Joint Outcomes ($n=53$): Total global WOMAC scores improved remarkably from a baseline mean of 50.5 down to 13.8 at 6 months, and further declined to an exceptional 7.8 at the 2-year mark—yielding a total clinical symptom reduction of 84.5%.

    • Pain Subscale: Decreased significantly by 94% from 10.1 at baseline to 0.6 at 24 months.

    • Stiffness Subscale: Decreased by 89% from 3.6 to 0.4.

    • Physical Function: Demonstrated an 81% improvement, dropping from 36.7 to 6.8.

  • Hip Joint Outcomes ($n=51$): Total global WOMAC scores displayed an identical significant positive path ($p=0.0001$), dropping from 58.4 at baseline to 14.8 at 6 months, and stabilizing at 9.1 at 2 years, marking an overall 84.4% symptom decrease.

    • Pain Subscale: Decreased by 79.5%, shifting from 12.2 down to 2.5 at 24 months.

    • Stiffness Subscale: Improved by 89%, decreasing from 4.7 down to 0.5.

    • Physical Function: Significantly improved by 85%, dropping from 41.4 to 6.2.

When compiling the total cohort ($n=104$), gender did not influence clinical success metrics ($p > 0.05$). The aggregate dataset highlighted a unified 2-year clinical efficacy rate of 84.5% ($54.3$ baseline down to $8.4$ final global score; $p=0.0001$).

Radiographic Changes in Joint Space width

Radiographic analysis utilizing an unpaired two-tailed t-test confirmed substantial structural enhancement 6 months post-intervention. Knee joints achieved a mean structural joint space extension of 2.02 mm ($p=0.0001$). Concurrently, hip joints experienced a highly statistically significant mean structural space widening of 1.64 mm ($p=0.0001$).

Discussion

The findings of this retrospective evaluation demonstrate that the concurrent deployment of autologous SVF, liquid C-PRF, and long-acting ALB-PRF gel represents an effective biological therapeutic option for severe knee and hip osteoarthritis. This combined modality addresses a critical therapeutic gap for individuals who have exhausted standard conservative lines of management but wish to delay or entirely avoid total joint arthroplasty.

While previous research has focused on isolated short-term SVF applications, combining cell therapy with a long-acting platelet scaffold provides sustained clinical benefit over a 2-year period. Our clinical data indicates that knee joints responded with slightly higher efficacy across all measured WOMAC domains compared to hip joints. This clinical trend is mirrored in the radiographic data, where the structural joint space expansion was marginally less in hip joints (1.64 mm vs. 2.02 mm). This pattern is highly logical considering that native articular cartilage and the anatomical joint space within the acetabulofemoral complex are naturally smaller and more confined than those within the tibiofemoral complex.

Interestingly, the global WOMAC score improvements observed in this study directly parallel outcomes typically reported following successful total knee and hip replacement surgeries. However, the internal distribution of these improvements exhibits a complete inversion: while post-surgical databases consistently report that hip replacements achieve superior and faster WOMAC outcomes compared to knee replacements, this biological therapy demonstrated higher overall relief scores in knee joints. Furthermore, unlike the rapid adjustments seen after major surgeries, biological joint regeneration takes longer to fully manifest; clinical improvements continue to develop past the 6-month post-injection period and reach peak efficacy at 2 years.

From a clinical safety perspective, a major advantage of this autologous approach is its minimally invasive nature and excellent safety profile. Because only the patient’s own cellular material and blood derivatives are utilized, the risk of immune rejection or severe graft-versus-host complications is virtually nonexistent. This provides a vital joint-preserving alternative, particularly for younger patients with severe OA who are often forced to delay joint replacement due to the limited lifespan of mechanical prostheses. It is worth noting, however, that while some research supports repeated cellular injections, recent findings have raised potential safety concerns, suggesting that multiple adipose-derived stem cell injections might induce secondary anti-histone H2B antibody production and trigger localized inflammatory flare-ups. This highlights the clinical advantage of our single-dose SVF protocol supported by a long-acting biological fibrin matrix.

Study Limitations

Despite the highly positive long-term trajectories recorded, certain limitations must be acknowledged. First, due to its retrospective design, the study lacks an independent control or placebo arm, which limits the ability to control for a potential placebo effect. Second, while WOMAC scores offer an indirect measure of functional joint mobility, explicit objective data regarding range of motion (ROM) in degrees was not collected. Third, although digital plain radiography effectively tracked joint space width variations, it cannot visualize subtle intra-cartilaginous soft tissue changes. Future prospective trials should consider incorporating 3D-FS-SPGR sequence magnetic resonance imaging (MRI) to map precise volumetric cartilage regrowth, despite its higher cost.

Finally, because patients who failed to adhere to the 5-week non-weight-bearing restriction were excluded, we lack comparative data to determine whether this strict off-loading phase is mandatory to achieve optimal structural cartilage repair. Given the varying clinical outcomes reported in existing literature, larger randomized controlled trials are required to standardize post-injection rehabilitation protocols.

Conclusion

In conclusion, autologous SVF combined with PRF and ALB-PRF is a highly effective, safe, and minimally invasive treatment for both knee and hip osteoarthritis. The long-term tracking confirmed significant reductions in clinical symptoms after 2 years, which were accompanied by measurable structural increases in joint space width on radiographic imaging. This combination represents a viable biological therapeutic option to delay or replace total joint arthroplasty.

Declarations

  • Ethics Approval: In accordance with the Ethics Commission of Stockholm (Sweden), retrospective database studies using fully anonymized data do not require formal ethical approval or specific informed patient consent. The study was conducted in strict accordance with the 1964 Declaration of Helsinki.

  • Consent for Publication: Not applicable; all presented data was strictly anonymized prior to extraction.

  • Funding: The author received no external financial support for the research, execution, or publication of this article.

  • Competing Interests: The author declares no competing financial or professional interests.

  • Authors’ Contributions: All literary design, clinical text extraction, literature reviews, statistical mapping, and final drafting were executed entirely by TO.

  • Data Availability: All underlying datasets generated and analyzed during this study are available from the corresponding author upon reasonable request.

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