How does tendon healing work?
Tendon healing is a staged biological repair process that is often incomplete after injury or surgical repair. This page outlines the mechanism and summarises laboratory and clinical research into biological adjuncts stu
Tendon healing is the biological process by which a damaged tendon restores continuity and load-bearing capacity. It is classically described as a three-phase continuum: an inflammatory phase, a proliferative or reparative phase, and a remodelling phase. The process is driven by a coordinated sequence of haemostasis, immune cell recruitment, fibroblast proliferation, and matrix deposition, followed by slow reorganisation of collagen. In adult mammals, healing frequently results in mechanically inferior scar tissue rather than true regeneration, and the repaired tendon remains at risk of re-rupture. The identifiers used to describe tendon healing are clinical and histological rather than chemical: no single sequence, formula, or molecular weight defines the process. The work described below centres on growth factor signalling and peptide-based adjuncts studied in tendon and tendon-to-bone healing models.
Research into tendon healing centres on growth factor and cytokine signalling pathways, including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP), and macrophage polarisation pathways, as well as on peptide and hormone adjuncts tested in animal and early human studies.
Research Studies
BPC-157 and tendon healing after rotator cuff repair in humans
BPC-157 is a synthetic pentadecapeptide that has shown regenerative and anti-inflammatory effects in preclinical animal models of musculoskeletal injury. A randomised, double-blind, placebo-controlled pilot trial is investigating its effects on tendon healing and functional recovery following arthroscopic rotator cuff repair (aRCR). Twenty patients undergoing aRCR are to be randomly assigned to receive either BPC-157 or a saline placebo, self-administered as daily subcutaneous injections for 90 days after surgery, with all other care following the standard postoperative protocol [1]. At the time of the registry record, BPC-157 had not been studied in formal human clinical trials [1].
BPC-157, TB-500, and Achilles tendon healing in rats
A preclinical study evaluated BPC-157, synthetic thymosin beta-4 (TB-500), and their combination on Achilles tendon healing in a rat model using biomechanical, histopathological, histochemical, and immunohistochemical analyses. Thirty-two male Sprague-Dawley rats were used [6]. This evidence is animal-only and does not establish effects in humans.
Autologous microfragmented lipoaspirate tissue and long-term rotator cuff repair outcomes
A prospective randomised controlled single-blind clinical trial evaluated the safety and efficacy of autologous microfragmented lipoaspirate tissue in arthroscopic rotator cuff repair. 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, measured by Constant-Murley score (CMS) at least 5 years after surgery [2].
Metformin and chronic Achilles tendon pain
An exploratory clinical trial is examining the effect of oral ingestion of metformin (OIM) in non-diabetic patients with chronic Achilles tendon pain. The trial has two aims: to assess the effects of OIM treatment on tendon pain, and to determine the effects of metformin capsules on tendon healing and repair. Twenty participants are to be treated with metformin capsules for 16 weeks combined with a home exercise programme, and a comparison group of 20 participants is to receive placebo tablets with the same home exercise programme [3].
Sex hormone supplementation and rotator cuff repair in men
Shoulder tendon tears are a common cause of shoulder pain and disability, and after surgery the repaired tendon often does not heal. In a pilot study, men with low sex hormone levels are randomly assigned to receive sex hormone therapy or placebo pills while healing from tendon repair surgery in the shoulder. The investigators are testing whether increased sex hormone levels show promise in improving tendon healing and patient shoulder function and pain [4].
bFGF and VEGFA gene delivery to tendon and peritendinous tissues
Tendon healing is limited by inadequate vascularity and low cellularity within the tendon, whereas surrounding peritendinous tissues include vascular, stromal, and extrinsic reparative cells. Building on prior work involving tendon-only co-delivery of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA), a study reported that spatially distributed bFGF and VEGFA gene delivery to tendon and peritendinous tissues enhanced early tendon healing [5]. This evidence is preclinical.
BMP-7 and low-molecular-weight peptide solution in a rat rotator cuff tear model
Rotator cuff tears are the most prevalent shoulder pathology requiring surgery, yet high retear rates necessitate additional biological adjuncts. A study evaluated the effects of bone morphogenetic protein-7 (BMP-7) and low-molecular-weight peptide solution (LMWPS) on early tendon-to-bone healing in a rat model using histopathological and biomechanical methods [7]. This evidence is animal-only.
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 (RCT) model. The impact of GHRP-2 on M1 macrophage polarisation was determined in vitro using real-time polymerase chain reaction, Western blot, and immunofluorescence, and the study reported decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties [8]. This evidence is animal-only and in vitro.
Comparison of adjuncts studied in tendon healing
| Adjunct | Model | Primary outcome studied |
|---|---|---|
| BPC-157 | Human (aRCR pilot trial) | Tendon healing and functional recovery [1] |
| BPC-157, TB-500, combination | Rat Achilles tendon | Biomechanical and histopathological healing [6] |
| Autologous microfragmented lipoaspirate tissue | Human (aRCR trial) | Constant-Murley score at ≥5 years [2] |
| Metformin | Human (chronic Achilles tendon pain) | Tendon pain and healing [3] |
| Sex hormone therapy | Human (men with low sex hormone levels) | Tendon healing, shoulder function and pain [4] |
| bFGF and VEGFA gene delivery | Preclinical (tendon and peritendinous tissues) | Early tendon healing [5] |
| BMP-7 and LMWPS | Rat rotator cuff | Early tendon-to-bone healing [7] |
| GHRP-2 | Rat rotator cuff; in vitro | M1 macrophage polarisation; tendon-bone healing [8] |
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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.