The Science
What happens inside a joint after surgery, and what TX-33 is designed to do about it.
There is currently no approved drug that prevents scar tissue from forming inside joints after surgery or injury. TX-33 is an investigational intra-articular therapeutic designed to change that.
The problem
What is arthrofibrosis?
Arthrofibrosis is excess scar tissue inside a joint. When a joint is injured or operated on, the body's healing response can overshoot. Instead of clean repair, scar tissue builds up and stiffens the joint.
What it causes
Limited range of motion, chronic pain, joint stiffness, and functional deficits. In athletes, it extends recovery timelines and increases re-injury risk. In everyday patients, it can mean permanent loss of mobility.
Where it happens
After ACL reconstruction, meniscus repair, total joint replacement, rotator cuff surgery, elbow procedures, and other trauma. The underlying biology is the same: dysregulated fibrosis pathways that turn healing into scarring.
What exists today
Physical therapy, pain management, and additional surgery to remove scar tissue after it forms. No approved drug targets the root cause. As the AAOS noted in 2023, most biology-based orthopedic treatments still lack robust clinical evidence for routine use.
Rodeo SA, JAAOS, 2023;31(12):604-13 (PMID 37130369)
The approach
How does TX-33 work?
TX-33 is a combination of advanced biomaterials and a pharmaceutical-grade anti-fibrotic compound, delivered as an intra-articular therapeutic within a specific therapeutic window after injury or surgery.
Step 1
Joint trauma triggers a healing response
Surgery or injury sets off a cascade of biological signals. When healing goes unchecked, the result is arthrofibrosis: scar tissue that stiffens the joint, limits motion, and causes chronic pain.
Step 2
TX-33 intervenes in the therapeutic window
A combination of advanced biomaterials and a pharmaceutical-grade anti-fibrotic compound, delivered directly to the joint. The biomaterials control the release locally, limiting systemic side effects.
Step 3
Prevention, not treatment
TX-33 doesn't treat stiffness after it develops. It's designed to stop the molecular cascade before excess scar tissue forms. Joints heal the way they're supposed to.
Step 4
Patients recover with confidence
Less scar tissue means faster return to full range of motion, lower re-injury risk, and less time wondering if the body will cooperate. Paired with physical therapy.
The evidence
What does the clinical data show so far?
In a Phase 1/2 double-blind, placebo-controlled trial after laparoscopic myomectomy, an abdominal and pelvic surgery, 93% of patients (14 of 15) treated with L-alanyl-L-glutamine had no adhesions at follow-up surgery, compared with 41% (7 of 17) on placebo. No serious adverse events were reported.
L-alanyl-L-glutamine is the active compound in TX-33: a pharmaceutical-grade derivative of a molecule athletes have used for years for muscle recovery. It is now being engineered specifically for orthopedic applications: knee, shoulder, and elbow procedures.
TX-33 is investigational. It has not been approved by the FDA or any regulatory body for orthopedic use.
Chizen DR et al., European Journal of Obstetrics & Gynecology and Reproductive Biology, 2023;284:180-8. doi:10.1016/j.ejogrb.2023.03.032
Perspectives
What do surgeons and performance experts say?
Surgeons and recovery specialists who advise Temple OrthoBio see scar tissue as a central, unsolved problem in orthopedic recovery. Each person's relationship to the company is listed. Meet the full team.
"Dysregulation of the fibrosis pathways leads to significant pain and dysfunction. TX-33 has the potential to improve outcomes in millions of patients."
"TX-33 is a game changer. I see it being used in every surgery we do."
"I have personally dealt with scar tissue. It means everything. Whether you are on or off the podium. The margin at the elite level is so small."
FAQ
Frequently asked questions about TX-33
Short answers to the questions people ask most about TX-33, arthrofibrosis, and where the research stands.
What is TX-33?
TX-33 is an investigational intra-articular therapeutic designed to prevent scar tissue, called arthrofibrosis, from forming inside joints after surgery or injury. It combines advanced biomaterials with a pharmaceutical-grade anti-fibrotic compound, L-alanyl-L-glutamine.
Is TX-33 approved?
No. TX-33 is investigational. It has not been approved by the FDA or any regulatory body for orthopedic use.
What is arthrofibrosis?
Arthrofibrosis is excess scar tissue inside a joint. It forms when the healing response after injury or surgery overshoots, and it causes stiffness, limited range of motion, and chronic pain.
What clinical evidence exists for TX-33's active compound?
In a Phase 1/2 double-blind, placebo-controlled trial after laparoscopic myomectomy, 93% of patients (14 of 15) treated with L-alanyl-L-glutamine had no adhesions at follow-up surgery, compared with 41% (7 of 17) on placebo (Chizen et al., 2023). Orthopedic use is in development.
Which procedures is TX-33 being developed for?
TX-33 is being engineered for orthopedic applications, starting with knee, shoulder, and elbow procedures.
Who is developing TX-33?
Temple OrthoBio, spun off from Temple Therapeutics in 2024. Its co-founders are Sanj Singh, Dr. Riley J. Williams III (Chief, HSS Sports Medicine Institute), Jens Thies, Samuel Ogunsalu, and Jennifer Raoul.
Sources
Published research
The clinical trial of TX-33's active compound, plus the peer-reviewed work on fibrosis and arthrofibrosis that informs its orthopedic development.
- Chizen DR, Rislund DC, Robertson LM, Lim HJ, Tulandi T, Gargiulo AR, De Wilde RL, Velygodskiy A, Pierson RA. "A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions." European Journal of Obstetrics & Gynecology and Reproductive Biology, 2023;284:180-8. doi:10.1016/j.ejogrb.2023.03.032.
- Robertson LM, Fletcher NM, Diamond MP, Saed GM. "Evitar (l-Alanyl-l-Glutamine) Regulates Key Signaling Molecules in the Pathogenesis of Postoperative Tissue Fibrosis." Reproductive Sciences, 2019;26(6):724-33. doi:10.1177/1933719118789511. PMID 30185141.
- Morris JL, McEwen P, Letson HL, Dobson GP. "ACL reconstruction and creating a healing-permissive phenotype." Military Medicine, 2022;187(11-12):1310-7. PMID 35389483.
- Usher KM, Zhu S, Mavropalias G, Carrino JA, Zhao J, Xu J. "Pathological mechanisms and therapeutic outlooks for arthrofibrosis." Bone Research, 2019;7:9. PMID 30937213.
- Rodeo SA. "Status and outlook of orthobiologics." JAAOS, 2023;31(12):604-13. PMID 37130369.
- Punzi L, et al. "Pathogenic mechanisms and inflammation in post-traumatic arthritis." RMD Open, 2016;2(2):e000279. PMID 27651925.
- Ramos MS, Pasqualini I, Surace PA, Molloy RM, Deren ME, Piuzzi NS. "Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review." JBJS Reviews, 2023;11(12):e23.00140. doi:10.2106/JBJS.RVW.23.00140. PMID 38079496.
- Ghosh N, Bregere C, Bustos P, Guzman R. "L-Ala-L-Gln Suppresses Hypoxic Phenotype and Fibrogenic Activity of Rat Perineurial Fibroblasts." CNS & Neurological Disorders - Drug Targets, 2023;22(5):761-73. doi:10.2174/1871527321666220414094149. PMID 35431004.
I'm Back!™
The science exists so the next athlete who goes down can say two words.
That's what 13 years of research is for.