Chinese expert consensus on the clinical application of stromal vascular fraction combined with bone marrow flushing for osteonecrosis of the femoral head

Abstract

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease that leads to severe dysfunction of the hip joint in young and middle-aged patients. Its core pathological mechanism lies in the interruption of blood supply to the femoral head and an imbalance in bone repair capacity. Traditional hip-preserving treatment methods face many limitations in promoting effective repair of the necrotic area. With the rapid development of regenerative medicine, stromal vascular fraction (SVF) therapy, due to its rich content of various repair cells and growth factors, provides a highly promising new strategy for promoting angiogenesis and bone tissue regeneration in the necrotic area. Bone marrow flushing, as a key auxiliary means to optimize the local repair microenvironment, can further enhance the therapeutic effect when combined with SVF. This expert consensus aims to systematically review the current evidence-based medical evidence and clinical practice experience of SVF combined with bone marrow flushing in the treatment of ONFH, and to clarify the core norms and operational standards for its clinical application. The article will focus on in-depth elaboration of the indications and contraindications for SVF therapy, the standardized preparation and quality control system of cell preparations, key technical points of clinical minimally invasive surgical operations (including bone marrow flushing standards), multi-dimensional efficacy evaluation methods, and prevention and management strategies for potential complications. It is intended to provide clinicians with a set of standardized and scientific practical guidelines, ultimately promoting the safe, standardized, and effective application of SVF combined with bone marrow flushing technology in the field of ONFH treatment.

Graphical abstract

1. Consensus background

Osteonecrosis of the femoral head (ONFH) is a common and clinically challenging orthopaedic disorder characterized by impaired blood supply to the femoral head and subsequent bone cell death [1]. It predominantly affects middle-aged males, with external injury, long-term hormone use, ethanol intoxication, and decompression sickness being the main pathogenic factors [[2], [3], [4]].Although ONFH predominantly affects middle-aged males, the female could not be ignored due to the huge population size. Indeed, women have a lower overall incidence of ONFH (The prevalence rate among female is between 1/4 and 1/2 that of male among different populations.) [5]. However, female ONFH might tend to be more insidious, severe, and clinically underdiagnosed due to the following factors: late onset and delayed diagnosis, rapid progression after menopause and other high-risk conditions [6]. Currently, there are various clinical treatment options for ONFH, but no unified standard has been established, especially in the field of non-surgical treatment, where standardized guidance documents are lacking [7]. With the development of regenerative medicine, adipose stromal vascular fraction (SVF), a biological agent extracted from adipose tissue rich in various cellular components (such as stem cells, stromal cells, immune cells, endothelial cells, etc.), has shown promising application prospects in the treatment of ONFH [[8], [9], [10]].

In patients with osteonecrosis of the femoral head (ONFH), the necrotic area of the femoral head is often accompanied by bone marrow edema, blood stasis, accumulation of inflammatory factors, and residual necrotic tissue fragments, forming a local microenvironment unfavorable for bone repair [11]. Simple stromal vascular fraction (SVF) transplantation is insufficient to fully exert its biological functions [12]. Bone marrow flushing is intended to optimize the local intraosseous microenvironment by mechanically removing stagnant blood, necrotic debris, and inflammatory exudates from the necrotic region [13]. This rationale is supported by previous evidence indicating that ONFH is associated with venous stasis, increased intraosseous pressure, impaired blood flow, and inflammatory changes within the femoral head. In addition, bone marrow edema in ONFH has been associated with inflammation, fibrosis, oxidative stress, and increased osteoclast activity [14]. Therefore, when combined with core decompression, low-pressure bone marrow flushing may help reduce local congestion and inflammatory burden, thereby creating a more favorable environment for subsequent SVF implantation and bone repair [15]. Clinical studies have confirmed that compared to simple SVF treatment, bone marrow flushing combined with SVF transplantation can more significantly alleviate patients' pain symptoms, improve hip joint function, and reduce the risk of femoral head collapse. Particularly in cases with significant bone marrow edema or inflammation response around the necrotic lesion, the synergistic therapeutic effect is more prominent [16].

However, there are still many issues with the current combined treatment regimen in clinical applications, such as the lack of standardization in SVF extraction and preparation protocols, the absence of standardized operational parameters for bone marrow flushing (e.g., flushing pressure, flushing volume, flushing time), significant variations in treatment protocols (e.g., injection dose, injection site, treatment cycle), and inconsistent efficacy evaluation indicators, all of which severely hinder the standardized promotion and application of this technology [17].

To address the above issues and promote the standardization and scientific development of SVF combined with bone marrow flushing in the treatment of ONFH, experts in the fields of regenerative medicine, orthopedics, and rehabilitation medicine in China jointly initiated this effort. Based on high-level evidence-based medicine evidence published domestically and internationally (including randomized controlled trials, long-term follow-up studies, etc.), combined with domestic clinical practice experience, and after multiple expert meetings, questionnaire surveys, and peer reviews, the "Chinese Expert Consensus on the Clinical Application of Stromal Vascular Fraction Combined with Bone Marrow Flushing for Osteonecrosis of the Femoral Head" was finally formulated. This consensus aims to provide clear diagnostic and therapeutic guidance for clinicians, standardize the clinical application of SVF combined with bone marrow flushing in the treatment of ONFH, delay disease progression, postpone or even avoid artificial joint replacement surgery, and improve patient prognosis [18].

2. Methodology

This consensus was jointly initiated and developed by experts in the fields of regenerative medicine, orthopedics, and rehabilitation medicine in China. The entire process adhered to the principles of evidence-based medicine and integrated clinical practical experience. The final document was formed through systematic literature retrieval, multi-dimensional evidence collation, three rounds of expert surveys, and thematic discussions. The specific implementation process is as follows.

2.1. Literature retrieval and screening

Retrieval Databases: Comprehensive searches were conducted in major international databases, including PubMed and Web of Science, and Chinese databases, including China National Knowledge Infrastructure (CNKI) and Wanfang Database. Guidelines and consensus documents issued by relevant professional societies in the fields of orthopedics and regenerative medicine in China were also included.

Search Terms: Chinese search terms included stromal vascular fraction, SVF, adipose-derived stromal vascular fraction, osteonecrosis of the femoral head, ONFH, bone marrow flushing, hip-preserving therapy. English search terms included stromal vascular fraction, SVF, adipose-derived stromal vascular fraction, osteonecrosis of the femoral head, ONFH, bone marrow flushing, hip-preserving therapy. There were no language restrictions. High-level evidence-based medical evidence such as randomized controlled trials, long-term follow-up studies, systematic reviews, and meta-analyses were prioritized for inclusion.

After initial screening by title and abstract, followed by full-text re-screening, literature with incomplete data, duplicate publications, or excessively low quality was excluded. Ultimately, 10 high-quality relevant articles were included, providing the core evidence-based basis for the development of this consensus.

To provide an overview of current evidence, representative domestic and international studies on biological and combined hip-preserving treatment strategies for ONFH are summarized in Table 1.

Table 1.

Representative studies on biological hip-preserving strategies for ONFH.

Study	Study design	Sample size	Intervention	Evidence levela	Consensus recommendation	Key findings	Relevance to this consensus
Hernigou and Beaujean, 2002 [19]	Prospective clinical series	116 patients/189 hips	Core decompression combined with autologous bone marrow grafting	Level III (Prospective cohort)	Cell-based augmentation is recommended for appropriately selected early-stage ONFH before femoral head collapse.	Autologous bone marrow grafting showed better results when performed before femoral head collapse, supporting the rationale for biologically augmented hip-preserving surgery.	Foundational long-term clinical evidence for cell-based hip preservation.
Pepke et al., 2016 [20]	Randomized prospective clinical stud	24 patients	Core decompression plus bone marrow aspirate concentrate	Level II (Randomized prospective study)	Autologous cell therapy may be considered as an adjunct to core decompression.	The trial evaluated safety and clinical/radiological outcomes of BMAC injection during core decompression.	Provides randomized evidence for BMAC-augmented decompression.
Hong et al., 2023 [21]	Clinical study	Early-stage ONFH cohort	Adipose-derived SVF injection following core decompression and artificial bone graft implantation	Level IV (Clinical cohort)	SVF represents a promising biologic adjunct for hip-preserving surgery.	The study specifically evaluated adipose-derived SVF injection after core decompression and artificial bone grafting in ONFH.	Directly relevant to SVF-based hip-preserving treatment.
Liang et al., 2023 [22]	Clinical study	ARCO II–IIIA nontraumatic ONFH cohort	Autologous platelet-rich plasma and bone marrow mononuclear cells combined with core decompression	Level IV (Clinical cohort)	Combination biologic therapies may improve regenerative potential but require further validation.	Reported clinical outcomes of PRP plus bone marrow mononuclear cell grafting combined with core decompression.	Supports combined biologic augmentation strategies in Chinese ONFH patients.
Tantuway et al., 2024 [23]	Prospective/clinical follow-up study	ONFH patients treated with autologous SVF	Mechanically isolated autologous SVF intraosseous implantation	Level IV (Prospective clinical study)	Mechanical SVF preparation is an acceptable alternative where enzymatic processing is unavailable.	Mechanically isolated autologous SVF showed sustained functional improvement and acceptable safety during long-term follow-up.	Supports mechanical SVF preparation and intraosseous implantation.
Ma et al., 2025 [24]	Clinical study	Nontraumatic ONFH cohort	Double-channel core decompression combined with medullary cavity irrigation	Level IV (Clinical study)	Bone marrow flushing may be incorporated into hip-preserving procedures to improve the intraosseous microenvironment.	Double-channel core decompression combined with medullary cavity irrigation significantly alleviated hip pain and improved joint function in nontraumatic ONFH.	Direct evidence supporting the irrigation component of this consensus.
Zhang et al., 2026 [15]	Clinical study	148 patients/219 hips	Autologous adipose-derived SVF + calcium phosphate cement + core decompression	Level IV (Retrospective comparative study)	SVF combined with CPC may be considered as an adjunct to core decompression in early-stage ONFH.	SVF + CPC + CD was associated with lower radiographic progression, reduced THA conversion, and better pain and functional outcomes than CD alone.	Direct clinical evidence supporting an integrated mechanical–biological hip-preserving strategy using SVF, CPC, and core decompression for ONFH.
Zhu et al., 2021 [25]	Systematic review and meta-analysis	20 studies	Core decompression combined with adjunctive therapies, including cell therapy and other biologic strategies	Level I (Systematic review and meta-analysis)	Current evidence supports biological augmentation of hip-preserving surgery.	Meta-analysis evaluated whether adjunctive treatments combined with core decompression improve outcomes compared with core decompression alone.	compared with core decompression alone. Provides synthesized evidence for biologically augmented decompression.
Li et al., 2023 [26]	Systematic review and meta-analysis	18 studies; 916 patients/1257 hips	Stem cell therapy combined with core decompression	Level I (Systematic review and meta-analysis)	Stem cell augmentation is recommended as a promising adjunctive therapy, although standardized protocols remain necessary.	Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression, and conversion to THA.	High-level evidence supporting stem cell augmentation with decompression.
Tang et al., 2025 [27]	Systematic review and meta-analysis	954 subjects	Stem cell-based or biologic interventions for ONFH	Level I (Systematic review and meta-analysis)	Current evidence is encouraging; however, further multicentre randomized trials and long-term follow-up are required.	Recent meta-analysis summarized clinical evidence on biologic/cell-based therapy for ONFH.	Recent synthesized evidence for the field and useful for updating the consensus.

^aEvidence level: Level I = systematic review/meta-analysis; Level II = randomized controlled trial; Level III = prospective cohort study; Level IV = retrospective cohort study or clinical series; Level V = expert opinion.

2.2. Evidence extraction and analysis

An evidence evaluation team consisting of 5 core experts was established. Focusing on seven core dimensions—diagnosis, staging, and classification of ONFH; biological characteristics and mechanisms of action of SVF; preparation and quality control of SVF; operational standards for bone marrow flushing; indications and contraindications for combined therapy; efficacy evaluation; and prevention and management of complications—the team extracted, categorized, and graded the quality of evidence from the included literature. Combining actual clinical application scenarios, consensus points and controversial points from existing research were collated to form the core framework of the consensus draft.

2.3. Expert surveys and consensus formation

The expert group for developing this consensus consisted of experts from multiple fields in China, including regenerative medicine, orthopedics, and basic medicine. The draft revision and consensus unification were achieved through three rounds of external surveys and online thematic discussions:

First Round Survey: Based on the evidence collation results, an initial consensus draft was formed. A specialized questionnaire was designed and distributed online to all expert group members to solicit opinions and suggestions on the draft framework and core clauses. The draft was preliminarily revised based on the feedback.

Second Round Survey: Specialized opinion solicitation was conducted for key controversial content in the revised draft (such as SVF preparation operational parameters, bone marrow flushing pressure and dose thresholds, efficacy evaluation index systems, etc.). Experts were organized to provide written arguments, further refining the draft content and forming a solicitation draft.

Third Round Survey: The solicitation draft was publicly circulated for comments to relevant medical institutions and professional societies in the fields of orthopedics and regenerative medicine in China. Simultaneously, an online expert thematic discussion meeting was organized to conduct on-site argumentation and voting on controversial clauses. After reaching a consensus, the final consensus document was formed.

2.4. Finalization and review

After repeated proofreading by the drafting units (The Fourth Medical Center of PLA General Hospital, China–Japan Friendship Hospital) and review and confirmation by the core expert group, the final consensus document underwent peer review. Ultimately, this "Expert Consensus on the Clinical Application of Stromal Vascular Fraction (SVF) Combined with bone marrow flushing for the Treatment of Osteonecrosis of the Femoral Head" was formed.

3. Overview of SVF treatment for ONFH

3.1. Definition and biological characteristics of SVF

Stromal vascular fraction (SVF) is a heterogeneous cell population isolated from autologous adipose tissue through mechanical or enzymatic methods, primarily consisting of adipose-derived mesenchymal stem cells (ADSCs), endothelial progenitor cells, immune cells (such as macrophages and T cells), fibroblasts, and extracellular matrix components [28].Among these, ADSCs possess multipotent differentiation potential and can differentiate into osteoblasts, chondroblasts, etc., participating in bone tissue repair and regeneration; endothelial progenitor cells can promote angiogenesis, improving local blood supply in the femoral head; immune cells can regulate the local inflammatory microenvironment, reducing inflammatory responses. Additionally, a certain level of epidermal growth factor (EGF) can be detected in SVF [29]. EGF participates in cell proliferation and migration by activating EGFR-related signaling pathways, and its role in skin and soft tissue repair has been widely reported [30]. Compared to classic pro-angiogenic factors such as vascular endothelial growth factor (VEGF), the direct role of EGF in bone-cartilage repair still lacks consistent conclusions, but some studies suggest it may play a synergistic regulatory role in the SVF paracrine microenvironment by improving osteoprogenitor cell activity and chondrocyte metabolic state [31,32].

The preparation technology for SVF has gradually matured, and currently, commonly used extraction methods in clinical practice include mechanical grinding, collagenase digestion, and ultrasound-assisted extraction (such as the Australian patented technology Sahaj Therapy®). Different preparation methods have certain effects on the cell yield, viability, and cellular composition of SVF [21].

3.2. Mechanism of action of SVF in treating ONFH

The mechanism of action of SVF in treating ONFH primarily revolves around improving the local microenvironment of the femoral head and promoting bone repair and angiogenesis [33,34]. This includes the following specific aspects:

• 1.Promoting Angiogenesis: Endothelial progenitor cells within SVF can directly differentiate into vascular endothelial cells, forming new blood vessels. Simultaneously, cytokines secreted by SVF, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), can activate local vascular endothelial cells, promote angiogenesis, and improve the ischemic state of the femoral head [35].
• 2.Regulating the Inflammatory Response: A significant inflammatory response exists during the occurrence and progression of ONFH [36]. Immune cells within SVF (such as M2-type macrophages) can secrete anti-inflammatory effectors (e.g., IL-10, TGF-β), inhibit the release of pro-inflammatory factors (e.g., TNF-α, IL-6), reduce local inflammation, alleviate bone marrow edema, and create a favorable environment for bone repair [37].
• 3.Promoting Bone Tissue Repair: ADSCs within SVF can differentiate into osteoblasts under the induction of the local microenvironment, participating in the replacement and repair of necrotic bone tissue. Concurrently, osteogenic-related factors secreted by SVF, such as bone morphogenetic protein (BMP) and insulin-like growth factor (IGF), can promote the proliferation and differentiation of osteoblasts, accelerate new bone formation, and delay or prevent femoral head collapse [38].

3.3. Diagnosis, staging, and classification of ONFH

3.3.1. Diagnostic criteria

Comprehensive diagnosis is based on the internationally recognized Mont diagnostic criteria, integrating clinical symptoms, imaging examinations, and laboratory tests [39]:

• 1.Clinical Symptoms: Patients experience pain in the buttocks and thighs, which may radiate to the knee joint, accompanied by symptoms such as limited hip joint mobility, limping, and difficulty walking.
• 2.Imaging Examinations: Magnetic Resonance Imaging (MRI) is the preferred method for early diagnosis of ONFH, capable of displaying abnormal signals within the femoral head (e.g., low signal on T1-weighted images, "double-line sign" on T2-weighted images); X-ray film and Computed Tomography (CT) can be used for diagnosing mid-to-late stage ONFH, assessing femoral head morphology, osteonecrosis lesions, and changes in joint space;
• 3.Laboratory Tests: Generally, there are no specific indicators. If inflammation is present, a complete blood count may show elevated white blood cells, which can be used to rule out infectious diseases.

3.3.2. Staging criteria

The 2019 revised Association Research Circulation Osseous (ARCO) staging system was used to evaluate disease severity according to radiographic, CT, MRI, and bone scan findings, as well as the presence and extent of femoral head depression or osteoarthritic changes. The detailed ARCO staging criteria are summarized in Table 2 [40].

Table 2.

Association Research Circulation Osseous (ARCO) Classification System 2019 revised version.

Stage	Findings
I	X-ray is normal, but either magnetic resonance (MRI) or bone scan is positive
II	X-ray abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head), but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head
IIIa (early III)	fracture in the subchondral or necrotic zone as seen on x-ray or computed tomography (CT); early, femoral head depression ≤ 2 mm
IIIb (late III)	late, femoral head depression > 2 mm
IV	X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction.

3.3.3. Classification criteria

Lesion location and extent were assessed according to the China–Japan Friendship Hospital (CJFH) classification, which categorizes ONFH into medial, central, sub-lateral, extreme lateral, and whole femoral head types. The detailed CJFH classification criteria are summarized in Table 3 [41,42].

Table 3.

China–Japan Friendship hospital classification system for ONFH.

Type	Findings
M	The necrotic lesion is located in the medial region of the femoral head
C	The necrotic lesion is located in the central region of the femoral head.
L1	The necrotic lesion involves the sub-lateral region of the femoral head.
L2	The necrotic lesion involves the extreme lateral region of the femoral head.
L3	The necrotic lesion involves the entire femoral head.

In addition, the Japanese Investigation Committee (JIC) classification was used to evaluate weight-bearing involvement and collapse risk. The detailed JIC classification criteria are summarized in Table 4 [43].

Table 4.

Japanese Investigation Committee (JIC) classification system.

Type	Description
A	lesions occupied the medial one-third or less of the weight-bearing
B	lesions occupied medial two-thirds or less
C1	lesions occupied more than the medial two-thirds but not extending laterally to the acetabular edge
C2	lesions occupied more than the medial two-thirds and extending laterally to the acetabular edge

4. Consensus on the application of SVF in the treatment of ONFH

4.1. Indications and contraindications

• 1.Indications

Definitive diagnosis of ONFH, meeting the Mont diagnostic criteria;

ARCO staging is stage I-III, CJFH classification is type M, C, L1, L2 (the necrotic lesion does not involve the entire femoral head, and there is still potential for bone repair);

Age 12-55 years, with good compliance for hip-preserving treatment and strong desire for hip preservation;

Refusal or unsuitability for artificial joint replacement (e.g., young patients, those with surgical contraindications);

Poor response to non-surgical treatments such as medication and physical therapy, with disease progression.

• 2.Contraindications

Allergy to SVF or reagents used in the extraction process (e.g., local anesthetics, saline);

ONFH has reached ARCO stage IV, accompanied by severe joint space narrowing, osteoarthritis, or severe femoral head collapse that cannot be repaired;

Presence of severe dysfunction of vital organs such as the heart, liver, or kidneys, or blood coagulation disorders, making the patient unable to tolerate minimally invasive surgery;

Acute infection at the puncture site or systemic infection (e.g., fever, local redness, swelling, heat, pain);

Patients with malignant tumors or autoimmune diseases (e.g., systemic lupus erythematosus) in the active phase;

Patients with mental illness who cannot cooperate with treatment and follow-up.

4.2. Preparation and quality control of SVF

• 1.Adipose Tissue Harvesting

Donor Site Selection: Priority is given to areas rich in adipose tissue and convenient for harvesting, such as the abdomen and inner thigh;

Harvesting Method: Minimally invasive liposuction under local anesthesia is used to extract 50-100 mL of adipose tissue. Strict aseptic technique is followed during the procedure to avoid infection;

Adipose Tissue Processing: The extracted adipose tissue is immediately rinsed with saline to remove impurities such as blood and oil, and then placed in a sterile container for later use.

• 2.SVF preparation
• 1)Collagenase digestion method: When an enzymatic method is adopted, sterile clinical-grade or GMP-grade collagenase, or a validated collagenase-based enzyme mixture, should be used in accordance with the manufacturer's instructions, applicable local regulatory requirements, and institutional standard operating procedures. These regulatory requirements may include approval or acceptance by relevant authorities such as the National Medical Products Administration (NMPA), the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or the Pharmaceuticals and Medical Devices Agency (PMDA), as applicable. Published SVF protocols commonly use collagenase type I or collagenase-based mixtures at approximately 0.075%–0.2% or 1–2 mg/mL, with an enzyme solution volume close to the volume of washed adipose tissue, followed by incubation at 37°C for 30–60 min under gentle agitation. After digestion, the reaction should be terminated by dilution and/or neutralization using sterile saline, phosphate-buffered saline, autologous serum/plasma, or another validated neutralizing solution. The digest should then be filtered and washed repeatedly by centrifugation, usually 2–3 washing cycles, to remove residual collagenase and tissue debris. The final SVF product should undergo quality-control testing, including cell count, viability, sterility, endotoxin level, and, where feasible, residual enzyme assessment, before clinical use [44].
• 2)Mechanical Emulsification Method: In this method, SVF cells remain partially associated with the natural extracellular matrix microstructure, which may improve cell retention and preserve tissue-derived stromal components. In addition, the preparation process avoids the use of exogenous collagenase and in vitro culture techniques. It is a relatively simple and rapid clinical method that can be performed intraoperatively under sterile conditions without the need for a dedicated GMP cell-processing laboratory.

Briefly, adipose tissue is harvested from the thigh or abdomen using a sterile multi-hole liposuction cannula. The lipoaspirate should be processed as soon as possible after collection and maintained at room temperature during short-term intraoperative handling. The mixture may be allowed to stand for approximately 5–10 min to permit phase separation, after which the lower aqueous layer is discarded. Alternatively, the lipoaspirate may be centrifuged at approximately 400–1200 × g for 3–5 min at room temperature, depending on the processing device and institutional standard operating procedures, to remove the lower fluid layer and free oil. The remaining adipose tissue is then transferred into sterile syringes and mechanically emulsified by repeated passage between syringes through connectors of progressively smaller diameters or by using a validated mechanical emulsification device. The number of emulsification cycles should be standardized according to the device instructions and institutional protocol to obtain a uniform injectable product while avoiding excessive mechanical damage to cells.

After emulsification, the product may be filtered and/or centrifuged at approximately 1000–2000 × g for 3–5 min at room temperature to remove excess oil, fluid, and large tissue debris. The final SVF-containing fraction is collected and resuspended in sterile saline or another clinically approved carrier solution for subsequent implantation. During the entire process, sterile handling should be maintained, repeated temperature fluctuations should be avoided, and prolonged exposure at room temperature should be minimized. If short-term storage is unavoidable, the processed tissue or SVF suspension should be kept in a sterile closed container at 2–8°C and used within a validated timeframe according to institutional standard operating procedures.

To facilitate clinical selection and standardization, the relative advantages and limitations of enzymatic digestion and mechanical emulsification for SVF preparation are summarized in Table 5.

• 3.Quality Control

Table 5.

Comparison of enzymatic digestion and mechanical emulsification methods for SVF preparation.

Aspect	Enzymatic digestion	Mechanical emulsification
Main principle	Collagenase-mediated digestion of adipose extracellular matrix	Physical fragmentation, emulsification, filtration, and/or centrifugation
Cell yield	Generally higher nucleated cell yield	May be lower or more variable
Cellular release	More efficient release of stromal and vascular cell populations	Less complete cellular release but may preserve tissue niches
Extracellular matrix	ECM largely digested	ECM fragments are better preserved
Processing time	Usually longer	Usually shorter
Technical requirements	Requires enzyme control, neutralization, washing, and quality testing	Simpler equipment and workflow
Safety concerns	Residual collagenase, endotoxin, sterility, over-digestion	Product heterogeneity, tissue debris, variable yield
Regulatory considerations	May be more strictly regulated because exogenous enzymes are use	May have fewer concerns related to enzyme residues, depending on jurisdiction
Quality control	Cell count, viability, sterility, endotoxin, residual enzyme control	Cell count, viability, sterility, endotoxin, particle size/product consistency

Cell viability: The viability of SVF cells was detected using the trypan blue staining method, requiring a cell viability >85%;

Cell count: The concentration of SVF cells was measured using a hemocytometer or an automated cell counter to ensure the therapeutic dose reached 8.0×10ˆ7 cells/4-5 mL;

Microbial testing: After each batch of SVF preparation, samples must be taken for bacterial, viral, fungal, mycoplasma, and chlamydia cultures and related tests for later verification;

Endotoxin-free testing: The endotoxin content in SVF was detected using the limulus amebocyte lysate (LAL) method, requiring endotoxin <0.5EU/mL to avoid causing systemic inflammatory reactions [45,46].

Specimens retained for testing; if issues arise, close and continuous monitoring of the patient is required, along with necessary interventions.

• 4.Timeframe for SVF preparation and use:

To preserve cell viability and minimize contamination risk, adipose tissue processing should be initiated as soon as possible after tissue collection. For intraoperative clinical use, SVF should preferably be prepared and administered within the same operative session. In general, the interval from adipose tissue collection to SVF implantation should be minimized and preferably kept within 2–4 h, provided that the product is maintained under sterile and validated processing conditions. If temporary storage is unavoidable, the adipose tissue or SVF suspension should be stored in a sterile, closed container at 2–8°C and used only within a validated timeframe according to institutional standard operating procedures. Prolonged storage, repeated temperature fluctuations, or unvalidated cryopreservation should be avoided for fresh clinical application [47].

4.3. SVF Treatment operation standards

• 1.Preoperative Preparation

Patient Assessment: Complete laboratory tests such as complete blood count, coagulation function, liver and kidney function, infectious disease screening (hepatitis B, hepatitis C, syphilis, acquired immune deficiency syndrome (AIDS)), as well as imaging examinations like hip joint magnetic resonance imaging (MRI) and X-rays, to clarify the staging and classification of ONFH and rule out treatment contraindications.

Informed Consent: Provide detailed explanations to the patient and family members regarding the principles, procedures, expected efficacy, and potential risks (such as bleeding at the puncture site, infection, increased pain, etc.) of SVF treatment, and obtain signed informed consent.

Instrument and Medication Preparation: Prepare SVF preparation devices, puncture needles (21-23G), syringes, sterile dressings, local anesthetics (such as lidocaine), etc., ensuring that the instruments are properly sterilized.

• 2.Treatment Operation

Patient Positioning: Place the patient in a supine position with the affected hip slightly abducted and externally rotated. Mark the puncture point (generally selecting the body surface projection corresponding to the femoral head necrosis lesion, such as the lateral or anterior aspect of the hip).

Use a G-arm X-ray machine for fluoroscopic localization. Drill two 2.5 mm Kirschner wires into the femoral head necrosis area from below the lateral trochanter of the affected femur. After the working channel is established and partial necrotic tissue is removed, bone marrow flushing is performed to clear blood stasis, necrotic debris, and inflammatory exudates from the lesion area. The detailed flushing parameters, including pressure, volume, flow rate, duration, flushing solution, and safety precautions, are described in Section 4.4. During flushing, avoid high-pressure impact to prevent damage to the remaining normal bone tissue and blood vessels in the femoral head. After irrigation is complete, thoroughly drain any residual fluid from the cavity. Inject 5 mL of the processed SVF into the necrotic area along the bone grafting sleeve and implant self-setting calcium phosphate particles (diameter 2 mm, height 5 mm) into the ONFH area. Closely observe the patient's response during injection to avoid local tissue damage caused by excessive injection pressure. Under X-ray fluoroscopy, confirm that the necrotic area has achieved satisfactory support and reduction. Withdraw the bone grafting sleeve. After confirming no residual metal foreign bodies via another X-ray fluoroscopy, irrigate the wound with normal saline, disinfect the wound edges with alcohol, and perform full-thickness skin sutures [15,44].

For clarity, the major steps of the combined treatment procedure are summarized in Fig. 1.

Fig. 1.

Flow chart of the combined treatment procedure using stromal vascular fraction (SVF), bone marrow flushing, and self-setting calcium phosphate implantation for osteonecrosis of the femoral head (ONFH).

The procedure includes preoperative assessment and patient selection, adipose tissue harvesting, SVF preparation and quality control, fluoroscopy-guided establishment of the decompression channel, bone marrow flushing and debridement of the necrotic region, SVF implantation, implantation of self-setting calcium phosphate particles, fluoroscopic confirmation.

4.4. Application of bone marrow flushing

Bone marrow flushing, as a key auxiliary procedure in SVF transplantation for the treatment of ONFH, removes necrotic cells and eliminates pro-inflammatory substances; clears inflammatory cells and inflammatory factors, thereby eliminating the inflammatory pathological environment; restores the connectivity of the porous medium structure of bone tissue, providing effective channels for the flow of nutrients and metabolites of transplanted cells; and offers effective space for the retention of transplanted cells, demonstrating clear clinical applicability [16].

Based on evidence-based medicine evidence and clinical practice experience, the following unified operational parameter standards are established:

• 1
  Core Operational Parameters

  • (1)
    Flushing Pressure

Recommended pressure range: Adopt a low-pressure pulse flushing mode, with pressure strictly controlled between 5 and 15 psi (0.05-0.15 atm).

Pressure control principle: Centered on "gentle perfusion, effective cleaning," avoid high-pressure impact (strictly prohibited from exceeding 20 psi) to prevent damage to the remaining normal trabecular bone structure and nutrient vessels of the femoral head, while also avoiding adverse reactions caused by flushing fluid leakage into the joint cavity or surrounding soft tissues due to excessive pressure.

• (2)Flushing Volume

Basic flushing volume: Adjusted according to the ONFH stage and the extent of the necrotic lesion, with a conventional cumulative flushing volume of 500-1000 mL.

Stage-specific adjustment plan:

ARCO stages I–II (early lesions): The necrotic area is relatively small; therefore, the flushing volume should be controlled at 500–600 mL to meet basic cleaning requirements.

ARCO III stage (intermediate lesions): The necrotic lesion expands and may be accompanied by significant bone marrow edema; increase the flushing volume to 700-900 mL.

For cases with severe bone marrow edema, blood stasis, or poor previous treatment outcomes: The volume may be increased to 900-1000 mL as appropriate to ensure thorough removal of metabolic waste and inflammatory factors within the lesion.

Termination criterion: The core judgment basis is "clear and non-turbid flushing outflow fluid, with no visible necrotic tissue fragments," rather than relying solely on a fixed fluid volume [48].

• (3)Flushing Time

Conventional flushing duration: 3-5 min, coordinated with flushing volume and flow rate.

Stage-specific adjustment plan:

ARCO I-II stages: 3 min, avoiding prolonged flushing that may lead to bone tissue dehydration or local microenvironment disruption.

ARCO III stage and cases with severe inflammation: 5 min, ensuring sufficient contact between the flushing fluid and the lesion area to enhance cleaning effectiveness.

Time control principle: Maintain "continuous slow perfusion" during flushing, avoid intermittent high-pressure spurts, and ensure that the flushing time for a single lesion area is not less than 2 min to guarantee no cleaning blind spots.

• 2
  Supporting operational parameters

  • (1)
    Flushing flow rate

Adopt uniform pulse perfusion, with the flow rate controlled at 200/min, including:

Early flushing (first 1 min): Flow rate 100-150 mL/min, gradually softening and loosening necrotic tissue fragments;

Mid-term flushing (core cleaning stage): Flow rate 150-200 mL/min, efficiently removing loosened fragments and inflammatory factors;

Final flushing (finishing stage): Flow rate 100-150 mL/min, gently flushing residual impurities to avoid secondary damage.

• (2)Flushing solution selection and temperature

Recommended flushing solution: 0.9% sterile saline (isotonic, non-irritating, avoiding impact on SVF cell activity);

Liquid temperature: 37°C ± 1°C (close to human body temperature), preventing low-temperature flushing solution from stimulating the bone marrow cavity and causing vasospasm, or high temperature affecting local tissue activity.

• (3)Flushing pathway and method

Pathway establishment: Establish a unidirectional flushing pathway through the bone grafting sleeve, ensuring the flushing solution forms a closed loop of "inflow - flow through the lesion - outflow" to avoid dead space residue;

Flushing method: Adopt a combined mode of "pulse perfusion + intermittent static placement", with 30 s of static placement after each 1 min of flushing, allowing the flushing solution to fully penetrate into the trabecular bone gaps, improving the detachment and removal efficiency of necrotic tissue fragments;

Operational technique: The direction of the flushing needle must precisely correspond to the femoral head necrosis lesion area, avoiding repeated adjustments that may cause bone tissue damage. Monitor the entire process under G-arm X-ray fluoroscopy to ensure the flushing range covers the entire necrotic area.

• 3Principle of Individualized Parameter Adjustment

Adjustment Based on Classification: For patients with JIC classification type C1 or C2 (involving the lateral weight-bearing area), the irrigation volume can be increased by 20% and the irrigation time extended by 1-2 min on the basis of conventional parameters, with a focus on enhancing cleaning in the weight-bearing area. For patients with type A (medial type), the flow rate can be appropriately reduced to 100-150 mL/min to minimize interference with normal bone tissue in non-weight-bearing areas.

Adjustment for Special Populations:

Elderly patients (≥60 years old): Reduce pressure to 5-12psi and flow rate to 100-150 mL/min to avoid damage due to decreased bone tissue elasticity.

Patients with mild coagulation function abnormalities: Shorten irrigation time to 2 min and reduce flow rate to 100-150 mL/min to decrease the risk of local bleeding.

5. Safety control parameters

Pressure Monitoring: During the irrigation process, a simple pressure gauge should be equipped; if conditions permit, pressure monitoring can be performed to display the perfusion pressure in real-time. Once it exceeds 20 psi, the operation should be stopped immediately to check whether the pathway is blocked.

Parameter Thresholds to Avoid Complications:

The peak pressure for a single irrigation must not exceed 25 psi.

The cumulative irrigation volume should not exceed 1200 mL.

The continuous irrigation time for a single site should not exceed 3 min.

Emergency Adjustment: If the patient experiences severe hip pain, blood pressure fluctuations, or extravasation of irrigation fluid is observed under fluoroscopy during the irrigation process, the pressure should be immediately reduced (to below 5 psi), the flow rate slowed down, and the irrigation paused if necessary. Reassess whether to continue after symptoms have alleviated.

6. Postoperative efficacy evaluation and systematic follow-up

Usually, follow-ups are conducted at 4, 8, and 12 months postoperatively, and then every six months thereafter, to plot a complete efficacy curve and monitor long-term outcomes. The imaging evaluation system is the gold standard for judging structural repair [49]. X-rays are used for macroscopic observation to determine whether the femoral head contour remains intact, whether the joint space is narrowed, and whether there is progression of collapse. Magnetic resonance imaging (MRI) is the most critical imaging modality for evaluating ONFH. Its T1-weighted imaging (T1WI) and fat-suppressed T2-weighted imaging (T2WI) sequences can clearly show the extent of the necrotic lesion, changes in bone marrow edema, and the appearance and evolution of the repair zone (new bone formation) [50]. MRI can also be used to quantitatively measure parameters such as the necrotic angle and necrotic index, enabling more precise efficacy comparisons. For evaluating the repair of trabecular microstructure and the quality of bone healing, computed tomography (CT) three-dimensional reconstruction can provide more accurate information than X-rays, clearly showing the morphology and density of new trabecular bone. The comprehensive use of these clinical and imaging evaluation tools allows for a comprehensive and dynamic understanding of the hip joint's repair status after SVF treatment [51].

To unify efficacy evaluation criteria, standardize clinical study outcome reporting, facilitate data comparison across different studies, and support precise clinical decision-making, this consensus further defines the standardized composite efficacy endpoints for SVF treatment of femoral head necrosis, based on previous research evidence and clinical diagnosis and treatment experience. It establishes the criteria for determining treatment success and failure. The specific primary and secondary endpoints are defined as follows:

Primary endpoint (core criterion for treatment failure): Radiographic progression of the femoral head to the collapse stage (ARCO stage III or above) during postoperative follow-up, or the patient undergoing total hip arthroplasty due to disease progression of femoral head necrosis or severe impairment of hip joint function. Meeting either condition is defined as treatment failure. If neither of the above conditions occurs throughout the entire follow-up, the primary endpoint is considered achieved.

Secondary endpoint (criterion for clinical efficacy improvement): At the final postoperative follow-up assessment, the patient's Visual Analog Scale (VAS) pain score improves by ≥ 50% compared to the preoperative baseline level, and the Harris Hip Score improves to "good" or above. Meeting both criteria simultaneously is defined as clinical efficacy improvement, which can serve as an important clinical reference for treatment success [52,53].

The above composite endpoint system integrates imaging structural prognosis and clinical functional prognosis, enabling dual assessment of structural repair and clinical symptoms and functional rehabilitation. It can be standardized for evaluating the efficacy of SVF treatment for femoral head necrosis, effectively unifying research evaluation criteria, and providing standardized support for cross-comparison of multi-center research data, systematic evaluation of long-term efficacy, and individualized clinical diagnosis and treatment decision-making.

7. Prevention, identification, and management of complications

Although SVF treatment for ONFH is a minimally invasive hip-preserving surgery, it is still necessary to maintain a high level of vigilance for potential complications and establish standardized procedures for prevention, identification, and management [23]. Complications primarily involve the donor site, recipient site (Hip Joint), and potential risks related to the SVF product itself. Donor-site complications may arise from the liposuction or adipose tissue excision site used for SVF extraction. Common issues include hematoma, seroma, infection, local contour irregularities, and sensory abnormalities (such as numbness or pain) [23]. The key to prevention lies in meticulous surgical technique: tumescent fluid injection should be uniform, low negative pressure should be used for fat suction to minimize tissue trauma, and proper compressive dressing should be applied to the donor site postoperatively [54]. Management is primarily conservative and may include aspiration of large hematomas or seromas, together with physical therapy to promote absorption. If infection occurs, antimicrobial therapy should be administered according to culture and antimicrobial susceptibility testing results [55]. Recipient site (hip joint) complications are directly related to the surgical implantation procedure. These include puncture tract bleeding or Hematoma, intra-articular infection, iatrogenic femoral head or femoral neck fractures, and pain caused by transient intra-articular pressure elevation due to injection. The core of preventive measures relies on precise imaging guidance (e.g., C-arm fluoroscopy) to ensure a safe puncture path, using standardized techniques to avoid accidental damage to bone structures, and recommending that patients restrict weight-bearing for a short period (typically 6-12 weeks) postoperatively to reduce the risk of collapse and fracture [44,56]. If intra-articular infection occurs, it should be treated as an emergency, with immediate joint flushing, drainage, and systemic administration of sensitive antibiotics. Potential risks related to SVF, although rare, theoretically exist and require monitoring during long-term follow-up [57]. These risks include heterotopic ossification, autoimmunity, fat embolism, and the theoretical risk of tumor formation [58]. Strict quality control is the first line of defense against these risks, including ensuring the sterility, standardization, and safety of the SVF preparation process and cellular product. Standardized implantation techniques (such as avoiding intravascular injection) can reduce the risk of Embolism [59]. Furthermore, establishing a long-term clinical and imaging follow-up system is fundamental for monitoring delayed complications (such as heterotopic ossification or disease progression), ensuring the long-term safety of the treatment [60,61].

8. Clinical translation: challenges and opportunities

SVF combined with bone marrow flushing has potential as a minimally invasive hip-preserving strategy for early-to mid-stage ONFH [15]. However, its broader clinical application requires a standardized implementation pathway. First, regulatory compliance should be ensured because SVF preparation involves autologous cell processing. All procedures should follow applicable local regulatory requirements, ethical review standards, and institutional standard operating procedures, with defined quality-control criteria including cell count, viability, sterility, endotoxin level, residual enzyme control where applicable, and product consistency. Second, structured physician and technician training is necessary because the procedure involves adipose tissue harvesting, SVF preparation, fluoroscopy-guided decompression, bone marrow flushing, SVF implantation, and calcium phosphate implantation. Third, patient education and shared decision-making are essential to improve acceptance and establish realistic expectations regarding safety, cost, efficacy uncertainty, rehabilitation, follow-up, and the possibility of later conversion to total hip arthroplasty. Fourth, hospital resource allocation should be considered, including access to imaging guidance, sterile processing facilities, validated devices, quality-control testing, and multidisciplinary rehabilitation support. Therefore, early promotion may be most appropriate in tertiary hospitals or specialized hip-preservation centers, followed by gradual dissemination through standardized protocols, training programmes, quality assessment, and multicentre outcome registries. Future opportunities include the growing demand for hip-preserving treatment, advances in regenerative medicine, improved imaging-based risk stratification, and multicentre trials to define indications, optimize protocols, and evaluate cost-effectiveness.

9. Conclusion

From an expert perspective, the development of stromal vascular fraction (SVF) therapy for osteonecrosis of the femoral head (ONFH) marks a critical step in the transition of regenerative medicine from theoretical exploration to clinical practice within the field of orthopedic hip preservation. Its core value lies in utilizing the patient's own cellular resources, through a synergistic, multi-target, multi-mechanism approach—simultaneously promoting osteogenesis and angiogenesis—to provide a personalized treatment strategy with both safety and potential for early-stage and young-to-middle-aged ONFH patients. The success of this strategy is not accidental but is built upon a deep understanding of the disease's pathophysiology and the precise application of regenerative medicine principles.

Currently, the clinical translation efficacy of SVF therapy is highly dependent on a rigorous, standardized, full-process system. This includes precise patient selection based on imageology and clinical features, standardized SVF preparation and strict quality control in compliance with Good Manufacturing Practice (GMP), image-guided precise targeted transplantation, and evidence-based medicine-based rational combination treatment plans (such as combining core decompression and bone marrow flushing). Any oversight in any link may affect the final efficacy. Simultaneously, establishing systematic and objective postoperative evaluation and long-term follow-up mechanisms is crucial. This is not only necessary to verify its short-term safety and effectiveness but also serves as the cornerstone for accumulating high-level evidence-based medicine evidence and clarifying its long-term prognosis and cost-effectiveness ratio. Current evidence indicates that when performed by experienced teams in compliant medical environments, this therapy generally has good safety. However, its long-term efficacy, optimal cell dosage, and transplantation strategy still require confirmation through studies with larger samples and longer follow-up periods.

At the same time, this consensus objectively acknowledges the current limitations of clinical research and technical application of SVF in hip-preserving treatment for ONFH. Currently, high-quality, high-level evidence-based evidence supporting SVF clinical treatment remains relatively limited. Existing studies are mostly single-center, small-sample clinical observations, lacking large-sample, long-term follow-up controlled study data. The stability of long-term efficacy, risk of long-term complications, and cost-effectiveness ratio still require further verification. At the technical application level, there is currently no globally unified and comprehensive standardized SVF preparation system in clinical practice. Significant heterogeneity exists in cell extraction, purification, and quality control processes across different medical institutions and research centers, with substantial differences in key parameters such as cell activity and effective cell proportion, directly affecting the reproducibility of treatment outcomes. Additionally, clinically recommended key operational parameters and protocols, such as bone marrow flushing and combinational therapy, are mostly based on clinical expert experience and consensus summaries, lacking support from high-level evidence-based medicine derived from large-scale randomized controlled trials. Optimal operational thresholds, suitable patient populations, and combinational therapy regimens have not yet formed a unified standard. Furthermore, individualized treatment doses, transplantation frequencies, and targeted intervention strategies for ONFH patients with different etiologies and stages remain unclear, with considerable gaps in clinical data in these specific subfields.

Looking ahead, the further development of SVF therapy for ONFH requires balance and breakthroughs in three dimensions. First, at the level of mechanism research, it is necessary to deeply elucidate the specific mechanisms of action and synergistic networks of different cellular components within SVF (such as mesenchymal stem cells, endothelial progenitor cells, and immunomodulatory cells). This will help optimize cellular products and predict patient responses. Second, at the clinical research level, efforts should be made to design and implement more prospective, multi-centre, randomized controlled high-quality clinical trials to provide Level I evidence and clarify its efficacy differences in ONFH subgroups with different stages and etiologies. Finally, at the technical level, it is essential to continuously advance the standardization and innovation of preparation processes, quality control standards, and transplantation techniques (such as combining with biological scaffolds or growth factors) to ensure the reproducibility and reliability of the treatment. Through the synergistic advancement of deepening mechanisms, solidifying clinical evidence, and standardizing technical operations, SVF therapy has the potential to evolve from a promising option into a standardized, scalable, and important component of the hip preservation treatment system. This could thereby offer the possibility for more ONFH patients to delay disease progression, improve hip joint function, and ultimately postpone or avoid joint replacement.

Declaration of artificial intelligence (AI) and AI-assisted technologies in the writing process

We confirm that AI tools were used appropriately during manuscript preparation to assist with grammar correction and language polishing. These tools helped improve the text's clarity, accuracy, and fluency. The authors have nevertheless carefully reviewed and verified all AI-generated modifications to ensure scientific accuracy and consistency with the intended meaning.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix.

《Chinese Expert Consensus on the Clinical Application of Stromal Vascular Fraction Combined with Bone Marrow Flushing for Osteonecrosis of the Femoral Head》

Consensus Writing Unit: The Fourth Medical Center of the People's Liberation Army General Hospital; China–Japan Friendship Hospital.

Consensus Writers: Xin Wang (Fourth Medical Center of PLA General Hospital), Junming Zhang (Fourth Medical Center of PLA General Hospital)

Expert Panel Members.

Lead Expert:

Jiang Peng, Fourth Medical Center of PLA General Hospital.

Liming Cheng, China–Japan Friendship Hospital.

Guidance Experts: (in alphabetical order by surname)

Weiheng Chen Third Affiliated Hospital of Beijing University of Chinese Medicine.

Wei He First and Third Affiliated Hospitals of Guangzhou University of Chinese Medicine.

Zirong Li China–Japan Friendship Hospital.

Youwen Liu Henan Luoyang Orthopedic Hospital.

Ling Qin The Chinese University of Hong Kong.

Dewei Zhao Zhongshan Hospital Affiliated to Dalian University.

Consensus Development Expert Group (listed in alphabetical order by surname pinyin)

Liming Bian School of Bioengineering, South China University of Technology.

Sumin Bian Westlake University.

Yongping Cao Peking University Hospital.

Wei Chai The Fourth Medical Center of PLA General Hospital.

Wei Chen The Third Hospital of Hebei Medical University.

Xiantao Chen Henan Luoyang Orthopedic Hospital.

Ying Chen China–Japan Friendship Hospital.

Zhipeng Fan Beijing Stomatological Hospital, Capital Medical University.

Suping Fang Hangzhou Awei Life Technology Co., Ltd.

Bo Gao The First Affiliated Hospital of Air Force Medical University.

Fuqiang Gao China–Japan Friendship Hospital.

Zhen Geng Institute of Translational Medicine, Shanghai University.

Wenlong Gou Daping Hospital, Army Medical University.

Minghui Gu The First Affiliated Hospital of Sun Yat-sen University.

Wanshou Guo China–Japan Friendship Hospital.

Na Han Peking University People's Hospital.

Yangquan Hao Xi'an Honghui Hospital.

Xiaofeng Li The First Affiliated Hospital of Nanchang University.

Xiaohong Li School of Medicine, Tianjin University.

Jianhao Lin Peking University People's Hospital.

Xianzhe Liu Union Hospital, Huazhong University of Science and Technology.

Feng Lu Nanfang Hospital, Southern Medical University.

Yujiang Mao Beijing Jishuitan Hospital.

Jinhui Ma China–Japan Friendship Hospital.

Wenwei Qian Peking Union Medical College Hospital.

Jirong Shen Jiangsu Provincial Hospital of Traditional Chinese Medicine.

Jiacan Su Institute of Translational Medicine, Shanghai University.

Wei Sun Chengdu Baohuan Femoral Head Orthopedic Hospital.

Xu Sun Nanjing Drum Tower Hospital, Nanjing University Medical School.

Jinshu Tang The Fourth Medical Center of PLA General Hospital.

Aiyuan Wang The Fourth Medical Center of PLA General Hospital.

Cheng Wang Peking University Third Hospital.

Jian Wang Nanfang Hospital, Southern Medical University.

Kai Wang School of Basic Medical Sciences, Peking University.

Weiguo Wang China–Japan Friendship Hospital.

Xin Wang The Fourth Medical Center of PLA General Hospital.

Zheng Wang Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Zhiyong Wang The Second Affiliated Hospital of Inner Mongolia Medical University.

Jianzhong Xi School of Future Technology, Peking University.

Baoyong Yan Hebei Medical University.

Dehong Yang Department of Spinal Orthopedics, Nanfang Hospital, Southern Medical University.

Qiang Yang Beijing Friendship Hospital, Capital Medical University.

Jinghui Yao The Third Affiliated Hospital of Southern Medical University.

Dawei Zhang The First Affiliated Hospital of Air Force Medical University.

Yi Zhang Academy of Military Medical Sciences.

Houfeng Zheng The Second Affiliated Hospital of Soochow University.

Consensus Writing Secretariat Group (in alphabetical order by surname)

Huo Li Eighth Medical Center of PLA General Hospital.

Guangbo Liu Ninth Medical Center of PLA General Hospital.

Xiaohan Sun Fourth Medical Center of PLA General Hospital.

Yanbin Wu Fourth Medical Center of PLA General Hospital.

Junming Zhang Fourth Medical Center of PLA General Hospital.

Xuexin Zhang Fourth Medical Center of PLA General Hospital.