How Tendon Healing Changes with Age
Tendon healing capacity declines with age, but research into biological adjuncts—from peptides to hormones—is exploring whether these changes can be modified. This page summarizes the current clinical and preclinical evi
How Tendon Healing Changes with Age
Tendon healing is the biological process by which a damaged tendon restores its structure and function. It is formally known as tendon repair or tendinogenesis, and it falls within the class of musculoskeletal regenerative processes. Unlike some repair pathways, tendon healing is not defined by a single molecular formula or sequence; instead, it involves a coordinated cascade of cellular and molecular events. With age, this cascade becomes less efficient, leading to slower healing, weaker repaired tissue, and higher rates of re-rupture after surgical repair. The pathway centres on growth factor signalling—including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and bone morphogenetic protein (BMP) families—and on the inflammatory and vascular responses that support tendon-to-bone integration.
Age-related changes in tendon healing are driven by reduced cellularity, diminished vascularity, and altered growth factor availability. These changes are observed across species, but much of the mechanistic work has been conducted in animal models or in vitro systems. Human clinical trials are now beginning to test whether biological adjuncts can improve outcomes in older adults.
Research Studies
BPC-157 and rotator cuff repair in humans
A randomized, double-blind, placebo-controlled pilot trial is investigating BPC-157 for tendon healing and functional recovery after arthroscopic rotator cuff repair (aRCR) [1]. BPC-157 is a synthetic peptide that has shown regenerative and anti-inflammatory effects in preclinical animal models of musculoskeletal injury, but it has not yet been studied in formal human clinical trials [1]. The trial plans to enrol twenty patients undergoing aRCR, who will self-administer subcutaneous injections daily for 90 days following surgery [1]. This study is ongoing and results are not yet available.
Autologous microfragmented lipoaspirate tissue and long-term rotator cuff repair outcomes
A prospective randomized controlled single-blind clinical trial evaluated the safety and efficacy of autologous microfragmented lipoaspirate tissue in arthroscopic rotator cuff repair [2]. The primary hypothesis was that an intraoperative injection of autologous microfragmented adipose tissue, processed with an enzyme-free technology, could improve clinical outcomes of single-row arthroscopic rotator cuff repair as measured by the Constant-Murley score (CMS) at least 5 years after surgery [2]. This study addresses long-term healing in a human population, but its results are not yet reported in the evidence provided.
Metformin and chronic Achilles tendon pain
An exploratory clinical trial is testing oral metformin in non-diabetic patients with chronic Achilles tendon pain [3]. The trial has two aims: to assess the effects of oral metformin on tendon pain, and to determine its effects on tendon healing and repair [3]. Twenty participants will receive metformin capsules for 16 weeks combined with a home exercise program, while a comparison group of 20 participants will receive placebo tablets with the same exercise program [3]. This study is ongoing and no results are available.
Sex hormone supplementation and rotator cuff repair in men
A preliminary randomized trial is investigating whether sex hormone therapy improves tendon healing after shoulder tendon repair surgery in men with low sex hormone levels [4]. Participants are randomly assigned to receive sex hormone therapy or placebo pills while healing from tendon repair surgery [4]. The investigators will test whether increased sex hormone levels show promise in improving tendon healing, shoulder function, and pain [4]. This study is ongoing and results are not yet available.
bFGF and VEGFA gene delivery in tendon and peritendinous tissues
Preclinical research has explored spatially distributed delivery of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) genes to tendon and peritendinous tissues to enhance early tendon healing [5]. Tendon healing is limited by inadequate vascularity and low cellularity within the tendon, whereas surrounding peritendinous tissues include vascular, stromal, and extrinsic reparative cells [5]. This work builds on prior tendon-only co-delivery of bFGF and VEGFA, and it reports that targeting both tendon and peritendinous tissues may improve early healing in animal models [5].
BPC-157 and TB-500 in a rat Achilles tendon model
A study in rats evaluated the effects of BPC-157, synthetic thymosin beta-4 (TB-500), and their combination on Achilles tendon healing using biomechanical, histopathological, histochemical, and immunohistochemical analyses [6]. Thirty-two male Sprague-Dawley rats were used in this preclinical model [6]. The findings are specific to this animal model and may not translate directly to humans.
BMP-7 and low-molecular-weight peptide solution in a rat rotator cuff tear model
Preclinical research in rats assessed the effects of bone morphogenetic protein-7 (BMP-7) and a low-molecular-weight peptide solution (LMWPS) on early tendon-to-bone healing in a rotator cuff tear model [7]. Rotator cuff tears are the most prevalent shoulder pathology requiring surgery, yet high retear rates necessitate additional biological adjuncts [7]. This study evaluated histopathologic and biomechanical outcomes in an animal model, and its results are specific to that model [7].
GHRP-2 and tendon-bone healing in a rat rotator cuff tear model
A study explored the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear model [8]. The impact of GHRP-2 on M1 macrophage polarization was determined in vitro using real-time polymerase chain reaction, Western blot, and immunofluorescence [8]. The study reported that GHRP-2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in this animal model [8]. These findings are preclinical and have not been confirmed in humans.
Comparison of select studies
| Study | Intervention | Model/Population | Primary Outcome |
|---|---|---|---|
| [1] | BPC-157 | Humans (aRCR) | Tendon healing and functional recovery |
| [2] | Autologous microfragmented lipoaspirate tissue | Humans (aRCR) | Constant-Murley score at ≥5 years |
| [3] | Metformin | Humans (chronic Achilles tendon pain) | Tendon pain and healing |
| [4] | Sex hormone therapy | Men with low sex hormones (rotator cuff repair) | Tendon healing, shoulder function, pain |
| [6] | BPC-157, TB-500, combination | Rats (Achilles tendon) | Histopathology and biomechanics |
| [7] | BMP-7, LMWPS | Rats (rotator cuff tear) | Histopathology and biomechanics |
| [8] | GHRP-2 | Rats (rotator cuff tear) | M1 macrophage polarization, healing properties |
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Sources
- [1] Impact of BPC-157 on Recovery Following Rotator Cuff Repair Surgery
- [2] Long Term Clinical Outcome After Arthroscopic Rotator Cuff Repair Augmentation With Autologous Microfragmented Lipoaspirate Tissue
- [3] Managing Chronic Tendon Pain by Metformin
- [4] Sex Hormone Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial
- [5] Spatially distributed bFGF and VEGFA gene delivery to tendon and peritendinous tissues enhances early tendon healing.
- [6] Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study.
- [7] Effects of bone morphogenetic protein-7 and low-molecular-weight peptide solution on healing in a rotator cuff tear model: a histopathologic and biomechanical study in rats.
- [8] 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.