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Peptide Therapy in Musculoskeletal Medicine

Injectable and regenerative peptide therapies in orthopaedics and sports medicine — what the evidence shows for tendon, cartilage and bone healing, and where the hype outpaces the data.

19 citationsUpdated Sep 2026

For patients: a plain-language version of this topic is available. See the patient guide.

Overview

Injectable peptide therapy possesses significant therapeutic and regenerative potential, yet it remains largely experimental in sports medicine [1, 4]. Currently, there is a lack of evidence to support the clinical use of injectable peptides in orthopaedic and sports medicine [1]. Consequently, peptide supplements should not be recommended as a replacement or adjunct for existing orthopaedic standard of care due to the absence of robust efficacy and safety data [2]. While various materials are on the market, no clinical or experimental long-term data on soft tissue or bone reaction is available for many of them [12]. The use of BPC-157 for sports performance and recovery is not recommended because there are no randomized controlled trials investigating its use in human subjects, and the science is clearly lacking to determine its overall effectiveness, safety profile, and clinical indications [11].

BMP-2 and BMP-7 are the only growth factors that can be recommended based on level I studies [5]. BMP currently has two FDA-approved indications: treatment of open tibial fractures treated with intramedullary fixation and treatment of tibia long bone non-union [6]. Other therapeutic strategies, such as trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffold for microfracture augmentation, can be cost-effective ways to improve cartilage healing outcomes [10]. Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis, although a better understanding of exosome mechanisms and standardized isolation methods is required before clinical application [8].

Loss of function in musculoskeletal tissues initiates from either a failure of the cells that produce and maintain the extracellular matrix (ECM) or as a consequence of material failure of the ECM itself [24]. The last three decades have witnessed marked advances in the identification of candidate therapeutic cell populations to replace tissue formation capacity and in the development of new biomaterials to restore or direct the restoration of damaged ECM [24]. These therapeutic cell populations and new biomaterials can be applied alone or in combination to promote healing that alters the trajectory of disease, and they can potentially replace an entire tissue when damage has progressed to later stages [24]. GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight [9]. Peptides are being widely advertised and sold through social media, often with exaggerated claims and minimal regulatory oversight [7].

How It Works

Regulatory Status and Clinical Recommendations

Orthopaedic and sports medicine providers must understand the current lack of evidence to support the clinical use of peptide therapy [1]. Specifically, the science is lacking to determine the overall effectiveness, safety profile, and clinical indications for BPC-157 in sports enhancement in athletes [11].

FDA-Approved Indications

Only BMP-2 and BMP-7 can be recommended based on level I studies [5].

Mechanistic and Preclinical Findings

Preclinical data demonstrate distinct mechanistic benefits across various peptide applications. BMP-7 application significantly enhances the quality of tendon-to-bone healing by promoting structural maturation and functional stability in a rat rotator cuff tear model [18]. Similarly, GHRP-2 administration reduced M1 macrophage polarization and enhanced histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model [19].

In cartilage and spinal applications, functionalized self-assembled peptides promote the differentiation of ADSCs into nucleus pulposus-like cells [20]. Regarding spinal cord injury, axon preservation and minimal inflammation in animals treated with BDNF-incorporated hydrogel indicate the potentiality of the intervention for further evaluations in the path of developing efficient therapies for severe spinal cord injury [21]. However, locomotor functional recovery was not observed in animals treated with BDNF-incorporated hydrogel [21].

In an equine model, treatment of defects with only KLD or with only microfracture resulted in an improvement in clinical symptoms compared with no treatment [14]. The improvement in clinical symptoms from KLD or microfracture treatment likely resulted from different causes depending on the treatment [14].

Clinical and Experimental Applications

EGYFIL is safe and seems to reduce pain and stiffness in patients during the 3 days of treatment, already after 3 h from the first application [16]. Therapeutic strategies for microfracture augmentation, such as those using trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffolds, can be cost-effective ways to improve cartilage healing outcomes [10].

What the Evidence Shows

Clinical Recommendations and Safety

Current evidence does not support the use of BPC-157 for sports performance and recovery. This recommendation stems from the absence of randomized controlled trials investigating its use in human subjects [11].

Growth Factors and BMPs

Bone morphogenetic protein (BMP) currently holds two FDA-approved indications: treatment of open tibial fractures managed with intramedullary fixation and treatment of tibia long bone non-union [6].

Experimental and Preclinical Models

Preclinical data indicate that axon preservation and minimal inflammation in animals treated with BDNF-incorporated hydrogel suggest the potential of this intervention for further evaluation in developing efficient therapies for severe spinal cord injury [21]. In equine models, therapeutic strategies for microfracture augmentation, including trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffolds, represent cost-effective methods to improve cartilage healing outcomes [10].

Other Peptide Applications and Mechanisms

The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis [30].

Practical Considerations

Orthopaedic and sports medicine providers must understand the current lack of evidence to support the clinical use of peptide therapies [1]. In the context of cartilage defect management, treatment with only KLD or with only microfracture resulted in an improvement in clinical symptoms compared with no treatment [14].

Key Evidence

  • [L5] While peptide therapy may possess significant therapeutic and regenerative potential, it is critical that orthopaedic and sports medicine providers understand the current lack of evidence to support the clinical use of these peptides. [1] (10.1177/03635465251357593)
  • [L5] Because of the lack of robust efficacy and safety data, peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care. [2] (10.1177/03635465261464420)
  • [L5] Injectable peptides for sports medicine remain largely experimental. [4] (10.2106/jbjs.rvw.26.00027)
  • [Paper] Today only BMP-2 and BMP-7 can be recommended based on level I studies. [5] (10.1016/s0020-1383(08)70014-7)
  • [Paper] The use of BMP currently has two FDA-approved indications: treatment of open tibial fractures treated with intramedullary fixation and treatment of tibia long bone non-union. [6] (10.1016/s0020-1383(13)70008-1)
  • [Paper] Peptides are being widely advertised and sold through social media, often with exaggerated claims and minimal regulatory oversight. [7] (10.1177/2325967126s00290)
  • [L5] Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis, though a better understanding of their mechanisms and standardized isolation methods is required before clinical application. [8] (10.1016/j.jhsa.2023.11.016)
  • [Paper] While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. [9] (10.2106/jbjs.rvw.23.00167)
  • [L5] Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes. [10] (10.1177/03635465211021798)
  • [L5] The authors do not recommend the use of BPC-157 for sports performance and recovery because there are no randomized controlled trials investigating its use in human subjects, and the science is clearly lacking to determine the overall effectiveness, safety profile, and clinical indications for sports enhancement in athletes. [11] (10.1016/j.arthro.2024.09.005)
  • [Paper] However, various materials are on the market for which no clinical or experimental long-term data on soft tissue or bone reaction is available. [12] (10.1016/s0020-1383(02)00128-6)
  • [L5] Treatment of defects with only KLD or with only microfracture resulted in an improvement in clinical symptoms compared with no treatment; the improvement likely resulted from different causes depending on the treatment. [14] (10.2106/jbjs.m.01408)
  • [L4] EGYFIL is safe and seems to reduce pain and stiffness in patients during the 3 days of treatment, already after 3 h from the first application. [16] (10.1186/s12891-023-06903-y)
  • [L5] BMP-7 application significantly enhances the quality of tendon-to-bone healing by promoting structural maturation and functional stability. [18] (10.1016/j.jse.2026.04.003)
  • [L5] GHRP-2 administration reduced M1 macrophage polarization and enhanced histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model. [19] (10.1016/j.arthro.2024.11.094)
  • [L5] The functionalized self-assembled peptide promotes the differentiation of ADSCs into nucleus pulposus-like cells. [20] (10.1186/s13018-022-03102-8)
  • [L5] Although locomotor functional recovery was not observed, axon preservation and minimal inflammation in animals treated with BDNF-incorporated hydrogel indicate the potentiality of the designed intervention for further evaluations in the path of developing efficient therapies for severe spinal cord injury. [21] (10.1016/j.injury.2018.12.027)
  • [Paper] The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis. [30] (10.1186/s12891-021-04067-1)

References

[1] Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians. The American Journal of Sports Medicine. 2026. DOI: 10.1177/03635465251357593

[2] Peptide Supplements and Their Therapeutic Applications in Sports Medicine. The American Journal of Sports Medicine. 2026. DOI: 10.1177/03635465261464420

[4] Injectable Peptides in Sports Medicine: A Structured Narrative Review of Evidence, Safety, and Antidoping Implications. JBJS Reviews. 2026. DOI: 10.2106/jbjs.rvw.26.00027

[5] Carrier systems and application of growth factors in orthopaedics. Injury. 2008. DOI: 10.1016/s0020-1383(08)70014-7

[6] Clinical applications of growth factors in bone injuries: Experience with BMPs. Injury. 2013. DOI: 10.1016/s0020-1383(13)70008-1

[7] Paper 32. Performance & Promises: A Social Media Review of Alleged Indications, Risks and Usage of “Peptides” in Musculoskeletal Health. Orthopaedic Journal of Sports Medicine. 2026. DOI: 10.1177/2325967126s00290

[8] The Role of Exosomes in Upper-Extremity Tissue Regeneration. The Journal of Hand Surgery. 2024. DOI: 10.1016/j.jhsa.2023.11.016

[9] Glucagon-like Peptide-1 Agonists. JBJS Reviews. 2024. DOI: 10.2106/jbjs.rvw.23.00167

[10] Microfracture Augmentation With Trypsin Pretreatment and Growth Factor–Functionalized Self-assembling Peptide Hydrogel Scaffold in an Equine Model. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211021798

[11] Injectable Therapeutic Peptides—An Adjunct to Regenerative Medicine and Sports Performance?. Arthroscopy. 2024. DOI: 10.1016/j.arthro.2024.09.005

[12] Biodegradable implants in soft tissue refixation: Experimental evaluation, clinical experience, and future needs. Injury. 2002. DOI: 10.1016/s0020-1383(02)00128-6

[14] Effects of the Combination of Microfracture and Self-Assembling Peptide Filling on the Repair of a Clinically Relevant Trochlear Defect in an Equine Model. Journal of Bone and Joint Surgery. 2014. DOI: 10.2106/jbjs.m.01408

[16] A pre-market interventional, single-arm clinical investigation of a new topical lotion based on hyaluronic acid and peptides, EGYFILTM, for the treatment of pain and stiffness in soft tissues. BMC Musculoskeletal Disorders. 2023. DOI: 10.1186/s12891-023-06903-y

[18] Effects of BMP-7 and Low Molecular Weight Peptide Solution on Healing in a Rotator Cuff Tear Model: A Histopathological and Biomechanical Study in Rats. Journal of Shoulder and Elbow Surgery. 2026. DOI: 10.1016/j.jse.2026.04.003

[19] Growth Hormone–Releasing Peptide 2 May Be Associated With Decreased M1 Macrophage Production and Increased Histologic and Biomechanical Tendon‐Bone Healing Properties in a Rat Rotator Cuff Tear Model. Arthroscopy. 2024. DOI: 10.1016/j.arthro.2024.11.094

[20] Self-assembling peptides with hBMP7 biological activity promote the differentiation of ADSCs into nucleus pulposus-like cells. Journal of Orthopaedic Surgery and Research. 2022. DOI: 10.1186/s13018-022-03102-8

[21] Biofunctionalized peptide-based hydrogel as an injectable scaffold for BDNF delivery can improve regeneration after spinal cord injury. Injury. 2019. DOI: 10.1016/j.injury.2018.12.027

[24] Orthopaedic Basic Science Fifth Edition Print Ebook. Cells and Materials for Soft-Tissue Repair and Regeneration > Introduction.

[30] The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04067-1

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