Efficacy and Safety of Fibrin Intervertebral Injections for Back and Neck Pain: A Systematic Review

The report is a product of the VA/HSR Evidence Synthesis Program.

Efficacy and Safety of Fibrin Intervertebral Injections for Back and Neck Pain: A Systematic Review

Takeaway: Neck and back pain are leading causes of disability. Common causes of neck and back pain include damage or degeneration of spinal discs and the surrounding sheath, which may result in leakage from the cushioning disc. There is growing interest in less invasive treatments, including "regenerative" spinal injections. Fibrin is a naturally occurring protein in the body that promotes blood clotting and has been proposed to seal and heal discs, which can reduce pain. This review focused on the evidence for two fibrin injection systems for back and neck pain: BIOSTAT BIOLOGX intra-discal system (injection directly into the disc) and Discseel intra-annular fibrin injection system (injection into the disc sheath). Evidence regarding fibrin injections for back pain is limited in quantity and quality. However, in adults with chronic low back pain originating from one or more spinal discs, the BIOSTAT BIOLOGX intra-discal system does not decrease pain intensity or pain interference compared to intra-discal saline injection. Serious adverse events as well as any adverse events are common with intra-discal injection and may not differ between fibrin and saline. Evidence is very uncertain regarding the effectiveness and harms of the Discseel intra-annular fibrin injection system. There are no data for the BIOSTAT BIOLOGX intra-discal system or the Discseel intra-annular fibrin injection system in adults with neck pain. Prior to implementation of the BIOSTAT BIOLOGX system or the Discseel intra-annular fibrin injection system, evidence of effectiveness of fibrin injections (especially the Discseel intra-annular fibrin injection system) from large, double-blinded randomized controlled trials of individuals with chronic back or neck pain is needed.

Neck and back pain lead to more disability than any other medical condition. Common causes of neck and back pain include damage or degeneration of spinal discs and the surrounding sheath, which may result in leakage from the cushioning disc. There is growing interest in less invasive treatments, including "regenerative" spinal injections. Fibrin is a naturally occurring protein in the body that promotes blood clotting and has been proposed to seal and heal discs, which can reduce pain. In response to a request from VHA's Office of Integrated Veteran Care Clinical Determinations Unit and the Pain Management Opioid Safety and Prescription Drug Monitoring Program, HSR's Evidence Synthesis Program (ESP) in Minneapolis conducted a systematic review of literature on the efficacy and safety of two fibrin injection systems for back and neck pain: BIOSTAT BIOLOGX intra-discal system (injection directly into the disc) and Discseel intra-annular fibrin injection system (injection into the disc sheath). To identify relevant articles, the ESP team searched MEDLINE, CDSR, CENTRAL, and Scopus through June 26, 2025.

Summary of Findings

• The ESP team identified four relevant articles, describing three unique studies. Three of the publications evaluated BIOSTAT BIOLOGX fibrin intra-discal injection; one reported on Discseel intra-annular fibrin injection.
• Evidence regarding fibrin injections for back pain is limited in quantity and quality.
• There are no data for the BIOSTAT BIOLOGX intra-discal system or the Discseel intra-annular fibrin injection system in adults with neck pain.

BIOSTAT BIOLOGX Fibrin Intra-Discal Injection System

• In adults with chronic low back pain originating from one or more spinal discs, fibrin intra-discal injection using the BIOSTAT BIOLOGX system does not decrease pain intensity or pain interference compared to intra-discal saline injection (moderate to low certainty of evidence [COE]).
• At 26 weeks, evidence from one unpublished multisite randomized controlled trial (RCT; N=220) found no difference in the primary outcome of "subject success based on a composite of a minimum 30% decrease in low back pain, 30% improvement in function, maintenance of neurological status, no secondary interventions, and no serious adverse events" of BIOSTAT BIOLOGX intra-discal fibrin versus saline; point estimates for success favored saline.
• Serious adverse events as well as any adverse events are common with intra-discal injection and may not differ between fibrin and saline (low COE).
• Additional information is limited to one small, uncontrolled pre-post pilot study (N=15) and a review reporting longer-term results from a single site (N=13) of the multisite RCT.

Discseel Intra-Annular Fibrin Injection System

• In adults with chronic low back pain, the evidence is very uncertain regarding the effectiveness and harms of the Discseel intra-annular fibrin injection system.
• One uncontrolled, single-site case series (N=827) evaluated Discseel for chronic low back pain from baseline up to three years after treatment, with reported outcomes limited to those who completed both baseline and follow-up measures (a minority of the entire cohort). The lead author was founder/president of the Discseel company. Evidence was insufficient for all outcomes.

Implications

The results of this review will help inform development of a Clinical Determination and Indication document to determine if the procedures are effective and safe. If the procedures are determined to be effective and safe, the results will also help clinicians determine whether a Veteran meets the criteria for these procedures.

Limitations

Findings are limited by the amount and quality of published information. Patients were highly selected for inclusion in these studies and interventions were provided by a very limited group of trained and experienced clinicians. Pre-post, uncontrolled, and unblinded studies are unlikely to provide reliable effect estimates, especially for patient-reported outcomes where large placebo effects may occur. Applicability of findings to different fibrin injection systems, diagnostic criteria, individuals, or clinicians outside of these study settings is unknown.

Future Research

Prior to implementation of the BIOSTAT BIOLOGX system or the Discseel intra-annular fibrin injection system, evidence of effectiveness of fibrin injections (especially the Discseel intra-annular fibrin injection system) from large, double-blinded RCTs of individuals with chronic back or neck pain are needed.

Citation:

Ullman K, Zerzan N, Landsteiner A, Goldsmith E, Southwell B, Macedo F, Wilt TJ. Efficacy and Safety of Fibrin Intervertebral Injections for Back and Neck Pain: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-009; 2025.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/discseel.cfm (This report is available via intranet only.)