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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.

Overview

Orthopaedic and sports medicine providers must understand the current lack of evidence to support the clinical use of injectable peptide therapies [1]. While preclinical models demonstrate specific biological mechanisms, such as BMP-7 application enhancing tendon-to-bone healing quality in rat rotator cuff tear models [2], or GHRP-2 reducing M1 macrophage polarization and improving histologic and biomechanical healing properties in the same model [3], these findings do not yet translate to established clinical protocols. Similarly, therapeutic strategies for microfracture augmentation using trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffolds show potential as cost-effective methods to improve cartilage healing outcomes in equine models [4], and functionalized self-assembled peptides with hBMP7 activity promote ADSC differentiation into nucleus pulposus-like cells [5].

Clinical application remains limited by a lack of robust human data. There are no randomized controlled trials investigating the use of BPC-157 in human subjects, and the science is lacking to determine its overall effectiveness, safety profile, and clinical indications for sports enhancement in athletes [7]. Consequently, authors do not recommend the use of BPC-157 for sports performance and recovery [7]. In contrast, EGYFIL appears safe for treating pain and stiffness in soft tissues, with reductions in symptoms observed already after 3 hours from the first application and continuing during the 3 days of treatment [8].

For structural defects, treatment of trochlear defects with only KLD (self-assembling peptide) or only microfracture both resulted in improvement in clinical symptoms compared with no treatment in an equine model [6]. However, the improvement in clinical symptoms from KLD or microfracture treatment for trochlear defects likely resulted from different causes depending on the treatment [6]. These disparate findings underscore the need for rigorous clinical validation before widespread adoption of peptide-based interventions in musculoskeletal medicine.

How It Works

Injectable peptide therapy possesses significant therapeutic and regenerative potential [1]. Despite this potential, the clinical use of peptides currently lacks sufficient evidence to support their use in orthopaedic and sports medicine practice [1].

BMP-7: Application enhances the quality of tendon-to-bone healing by promoting structural maturation [2]. It also enhances the quality of tendon-to-bone healing by promoting functional stability [2].

GHRP-2: Administration reduces M1 macrophage polarization in a rat rotator cuff tear model [3]. This administration enhances histologic tendon-bone healing properties in a rat rotator cuff tear model [3]. Furthermore, GHRP-2 administration enhances biomechanical tendon-bone healing properties in a rat rotator cuff tear model [3].

Peptide Hydrogels: Microfracture augmentation with trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffold can improve cartilage healing outcomes [4]. Self-assembling peptides with hBMP7 biological activity promote the differentiation of ADSCs into nucleus pulposus-like cells [5]. BDNF-incorporated biofunctionalized peptide-based hydrogel preserves axons after spinal cord injury [9]. This hydrogel causes minimal inflammation in animals after spinal cord injury [9]. However, locomotor functional recovery was not observed in animals treated with BDNF-incorporated hydrogel [9].

KLD and Microfracture: Treatment of trochlear defects with only KLD results in an improvement in clinical symptoms compared with no treatment [6]. Treatment of trochlear defects with only microfracture results in an improvement in clinical symptoms compared with no treatment [6]. The improvement in clinical symptoms from KLD or microfracture alone likely results from different causes depending on the treatment [6].

BPC-157: BPC-157 is not recommended for sports performance and recovery due to the lack of randomized controlled trials in human subjects [7]. The science currently lacks evidence to determine the overall effectiveness, safety profile, and clinical indications for BPC-157 in sports enhancement [7].

EGYFIL: EGYFIL is safe for the treatment of pain and stiffness in soft tissues [8]. EGYFIL reduces pain and stiffness in patients during a 3-day treatment period [8]. EGYFIL reduces pain and stiffness in patients already after 3 hours from the first application [8].

What the Evidence Shows

Orthopaedic and sports medicine providers must understand the current lack of evidence to support the clinical use of injectable peptide therapies [1].

Preclinical Tendon and Bone Healing: 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 [2]. GHRP-2 administration reduced M1 macrophage polarization in a rat rotator cuff tear model [3]. GHRP-2 enhanced histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model [3].

Cartilage and Joint Surface Repair: 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 in an equine model [4]. Treatment of clinically relevant trochlear defects with only KLD (self-assembling peptide) resulted in an improvement in clinical symptoms compared with no treatment in an equine model [6]. Treatment of clinically relevant trochlear defects with only microfracture resulted in an improvement in clinical symptoms compared with no treatment in an equine model [6]. The improvement in clinical symptoms from KLD or microfracture treatment for trochlear defects likely resulted from different causes depending on the treatment [6].

Spinal and Neural Applications: Functionalized self-assembled peptides with hBMP7 biological activity promote the differentiation of ADSCs into nucleus pulposus-like cells [5]. Axon preservation was observed in animals treated with BDNF-incorporated biofunctionalized peptide-based hydrogel [9]. Minimal inflammation was observed in animals treated with BDNF-incorporated biofunctionalized peptide-based hydrogel [9]. Locomotor functional recovery was not observed in animals treated with BDNF-incorporated biofunctionalized peptide-based hydrogel [9].

BPC-157 and Sports Performance: There are no randomized controlled trials investigating the use of BPC-157 in human subjects [7]. The science is lacking to determine the overall effectiveness, safety profile, and clinical indications for BPC-157 use in sports enhancement in athletes [7]. The authors do not recommend the use of BPC-157 for sports performance and recovery [7].

Topical Therapies: EGYFIL, a topical lotion based on hyaluronic acid and peptides, is safe for the treatment of pain and stiffness in soft tissues [8]. EGYFIL reduces pain and stiffness in patients during the 3 days of treatment [8]. EGYFIL reduces pain and stiffness in patients already after 3 hours from the first application [8].

Practical Considerations

Orthopaedic and sports medicine providers must understand the current lack of evidence to support the clinical use of injectable peptide therapies [1].

Preclinical Evidence: 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 [2]. GHRP-2 Administration: Reduces M1 macrophage polarization [3] and enhances histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model [3]. Microfracture Augmentation: Strategies using trypsin pretreatment and growth factor–functionalized self-assembling peptide hydrogel scaffolds can be cost-effective ways to improve cartilage healing outcomes in an equine model [4]. Functionalized Peptides: Self-assembled peptides with hBMP7 biological activity promote the differentiation of ADSCs into nucleus pulposus-like cells [5]. KLD Treatment: Treatment of clinically relevant trochlear defects with only KLD (self-assembling peptide) resulted in an improvement in clinical symptoms compared with no treatment in an equine model [6]. Microfracture Treatment: Treatment of clinically relevant trochlear defects with only microfracture resulted in an improvement in clinical symptoms compared with no treatment in an equine model [6]. Mechanistic Differences: The improvement in clinical symptoms from KLD or microfracture treatment likely resulted from different causes depending on the treatment [6]. BDNF-Incorporated Hydrogel: Axon preservation was observed [9] and minimal inflammation was observed [9], but locomotor functional recovery was not observed in animals treated with BDNF-incorporated hydrogel [9].

Clinical Evidence and Recommendations: BPC-157: There are no randomized controlled trials investigating the use of BPC-157 in human subjects [7]. The science is lacking to determine the overall effectiveness, safety profile, and clinical indications for BPC-157 use in sports enhancement in athletes [7]. The authors do not recommend the use of BPC-157 for sports performance and recovery [7]. EGYFIL: Safe for the treatment of pain and stiffness in soft tissues [8]. Reduces pain and stiffness in patients during the 3 days of treatment [8] and already after 3 hours from the first application [8].

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. (10.1177/03635465251357593)
  • [L5] BMP-7 application significantly enhances the quality of tendon-to-bone healing by promoting structural maturation and functional stability. (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. (10.1016/j.arthro.2024.11.094)
  • [L5] Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes. (10.1177/03635465211021798)
  • [L5] The functionalized self-assembled peptide promotes the differentiation of ADSCs into nucleus pulposus-like cells. (10.1186/s13018-022-03102-8)
  • [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. (10.2106/jbjs.m.01408)
  • [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. (10.1016/j.arthro.2024.09.005)
  • [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. (10.1186/s12891-023-06903-y)
  • [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. (10.1016/j.injury.2018.12.027)

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] 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

[3] 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

[4] 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

[5] 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

[6] 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

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

[8] 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

[9] 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

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