Molecular Biomarkers and Advanced Intra-Articular Therapeutics in Temporomandibular Disorders: A Comprehensive Systematic Review

Authors

  • Omukalthum Alsadiq Basheesh Department of Oral and Maxillofacial Surgery Author
  • Mohamed Alhadi Abokris Faculty of Dentistry, Sabratha University, Sabratha, Libya Author

DOI:

https://doi.org/10.54361/LJMR.20.2.59

Keywords:

Temporomandibular Joint Disorders, Biomarkers; Platelet-Rich Fibrin (PRF, Platelet-Rich Plasma (PRP), Hyaluronic Acid, Arthrocentesis; Distraction Osteogenesis, Joint Ankylosis

Abstract

Background: Temporomandibular disorders (TMDs) comprise a heterogeneous spectrum of musculoskeletal and neuromuscular pathologies impacting approximately 31% of the global adult population. Traditional diagnosis relies on static imaging and subjective tactile standards, which fail to capture real-time enzymatic and metabolic changes driving tissue degradation. This systematic review synthesises recent clinical evidence to clarify diagnostic biological fluid markers, contrast long-term injection outcomes, evaluate bioengineered hybrid scaffolds, and establish definitive architectural sequencing for major craniofacial reconstructive surgery. Methods: Conducted in strict compliance with PRISMA 2020 guidelines and registered with PROSPERO, a systematic literature search was executed across 9 international databases up to 2026. Studies were restricted to parallel-group randomised controlled trials (RCTs), prospective split-mouth trials, and longitudinal cohort studies. Methodological quality was appraised using RoB 2.0 and ROBINS-I instruments, with evidence certainty graded under the GRADE framework. Results: Eighteen core publications representing 1,540 patients were systematically compiled. Molecular mapping verified that synovial fluid pro-inflammatory cytokines (IL-1β, TNF-α) and matrix metalloproteinases (MMP-1, -3, -9) serve as highly sensitive parameters reflecting active chondrocyte apoptosis. High-molecular-weight HA provides immediate physical lubrication but undergoes accelerated enzymatic washout. PRP achieves superior, durable long-term (12-month) biological modulation. The i-PRF + arthroscopy conjugate yielded the highest long-term mean difference in functional jaw mobility. For end-stage ankylosis with severe micrognathia, the simultaneous arthroplastic distraction (SAD) sequence demonstrated complete dominance. Conclusion: The management of TMDs necessitates a transition toward personalised molecular medicine and combined mechano-biological therapeutics. Synovial and salivary biomarker tracking offers superior real-time diagnostic value over structural imaging. The simultaneous execution of joint arthroplasty and distraction osteogenesis (SAD) is mandatory for end-stage osseous fusion to ensure long-term stability and permanent posterior airway space expansion.

Downloads

Download data is not yet available.

References

1. Xu Y, Chen M, Wang J. Synovial fluid tracking of primary inflammatory profiles, interleukins, and matrix metalloproteinases in progressive internal derangements. Arthritis Res Ther. 2021;23(1):114.

2. Derwich M, Mitus-Kenig M, Pawlowska E. Mechanisms of molecular signalling and salivary/synovial biomarker profiling in patients with temporomandibular joint arthralgia and osteoarthritis. Int J Mol Sci. 2023;24(8):7120.

3. Kukreja P, Kukreja BJ, Marrapodi MM, Ronsivalle V, Cicciù M, Minervini G. Efficacy of hyaluronic acid in temporomandibular disorders evaluated with diagnostic criteria for temporomandibular disorders (DC/TMD). J Oral Rehabil. 2025;52(2):254–265. doi:10.1111/joor.13840

4. Zotti F, Albanese M, Rodella LF, Nocini PF. Platelet-rich plasma in the treatment of temporomandibular joint dysfunctions: Narrative review. Int J Mol Sci. 2019;20(2):277.

5. Malcangi G, Inchingolo AD, Inchingolo F, Dipalma G. Cellular evolution and biochemical pathways from first-generation blood concentrates to second-generation liquid platelet-rich fibrin scaffolds. J Clin Med. 2023;12(14):4812.

6. Flores-Fraile J, López-Valverde N, de Sousa BM. Macromolecular mechanics and clinical parameters of high-molecular-weight hyaluronic acid in the management of temporomandibular internal derangements. J Oral Rehabil. 2025;52(4):310–322.

7. Soares M, Rocha S, Caramelo F. Head-to-head structural and symptomatic evaluation of hyaluronic acid viscosupplementation versus variable platelet-rich plasma configurations in TMJ osteoarthritis. Clin Oral Investig. 2022;26(9):5671–5685.

8. Nurlygaianov R, Akhmetov I, Sharafutdinova L. Molecular kinetics of concentrated autologous signalling networks in articular cartilage regeneration and synovial interleukin

9. downregulation. Cell Tissue Res. 2025;399(2):233–247.

10. Martins V, Santos R, Ferreira M. Fibrin architecture specifications and long-term growth factor kinetics of autologous liquid concentrates prepared via low-speed centrifugation. Biomater Res. 2026;30(1):89–102.

11. Quezada DL, López CL, Montini FC, Skarmeta NP. Effectiveness of intra-articular infiltration of platelet concentrates for the treatment of painful joint disorders in the temporomandibular joint: A systematic review. Med Oral Patol Oral Cir Bucal. 2024;29(3):e297–e304.

12. Orzeszek S, Malysa A, Jenca A Jr, et al. Autogenous injections in temporomandibular disorders: A systematic review. J Clin Med. 2025;14(18):6640.

13. Araújo JSG, de Oliveira da Rosa WL, Meirelles LAD, dos Santos MG, Boscato N. Effectiveness of platelet-rich fibrin for temporomandibular disorders management: A systematic review and meta-analysis. Oral Dis. 2026;32(2):288–299. doi:10.1111/odi.70089

14. Yörük G, Şimşek G, Kaya E. Dual-action deployment systems post-arthrocentesis: A randomised double-blind clinical trial combining autologous platelets with hyaluronan polymers in disc displacement without reduction. J Craniofac Surg. 2026;37(2):441–453.

15. Yehia M, Al-Moraissi EA, Said S. Epigenetic modification and extracellular matrix stabilisation in painful internal derangements: A randomised trial combining liquid i-PRF with ascorbic acid. Int J Oral Maxillofac Surg. 2026;55(2):201–214.

16. Nemeth K, Soltesz P, Fazekas A. Psychometric profiling and Oral Health-Related Quality of Life outcomes in patients undergoing intra-articular therapies. J Dent. 2024;141:104820.

17. Albert D, Muthusekhar MR. Controversies in the management of temporomandibular joint ankylosis using distraction osteogenesis – A systematic review. Natl J Maxillofac Surg. 2026;17(1):45–58.

Downloads

Published

02-07-2026

Issue

Section

Articles

How to Cite

1.
Basheesh O, Abokris M. Molecular Biomarkers and Advanced Intra-Articular Therapeutics in Temporomandibular Disorders: A Comprehensive Systematic Review. LJMR [Internet]. 2026 Jul. 2 [cited 2026 Jul. 5];20(2):406-11. Available from: https://ljmr.ly/index.php/ljmr/article/view/582

Similar Articles

51-57 of 57

You may also start an advanced similarity search for this article.