Tendon injuries are amongst the most frequent injuries in sport activities. Most tendon injuries result from a tear of tendon fibers due to overuse, aging or accident.
The healing and
recovery of a ruptured tendon is known to be difficult and the repair of a completely torn tendon often relies on surgery. Tendon is composed of cells (tendon fibroblasts) and extracellular matrix, containing mostly type I collagen, type III collagen and glycoproteins.
The process of tendon healing is classified into three stages:
During the regeneration stage, tendon fibroblasts migrate into
the injured site, multiply and produce different types of collagens and glycoproteins to form the extracellular matrix. This is a prolonged process and the healed tendon is always weaker than the tendon prior to injury [1].
Therefore, it is vital to develop a new therapeutic approach to accelerate the healing and/or improve the strength of tendon.
BPC-157 is a 15-amino-acid-long fragment of the body protection compound (BPC) isolated from the human gastric juice [2].
It is stable and resistant to hydrolysis or digestion by enzymes, which makes it a very robust molecule. Previous studies have demonstrated the promoting effect of BPC-157 on the healing of different tissues, including skin, mucosa, cornea, muscle, tendon, ligament, and bone in animal studies [3].
Scientists consider it a blueprint for an entirely new class of organ-protective/healing drugs, but research is still in the early stages.
BPC-157’s mechanisms of action
BPC-157 mechanism of action in promoting muscle and tendon healing is likely through triggering the formation of new blood vessels – a process called angiogenesis (by increasing VEGF).
VEGF (vascular endothelial growth factor) originally known as vascular permeability factor, is a signal protein produced by many cells that stimulates the formation of blood vessels. This explains its regenerative potential and why it might also help heal wounds, cuts, and other types of damage in the body [4].
BPC-157 may foster wound and tendon healing by blocking the growth-inhibiting effects of a specific molecule, called 4-hydroxynonenal [5].
In addition, it may specifically help tendons heal by causing tendon cells to make more receptors for growth signaling molecules. In effect, this allows tendon cells to grow and move during injury repair, thus speeding up
the recovery process [3].
It may also reduce inflammation, which is possibly involved in its effects on wounds, ulcers, and tissue protection [6].
Although the mechanisms of action for BPC-157 are not yet fully elucidated, both in the currently reviewed and other surrounding literature, some light has been shed on a few potential systems involving
nitric oxide (NO), the FAK-paxillin pathway, VEGF and the upregulation of growth hormone (receptor) [7].
Tendon and ligament healing
Research demonstrated that
injections with BPC-157 helped tendons heal almost completely in animals with injuries to their Achilles tendons, whereas control animals did not make full recoveries [4].
BPC-157 appears to allow tendon fibroblasts to grow and spread faster, although this effect may not persist in the fibroblasts alone, suggesting other cells may be required for this effect or BPC-157 may work by negating suppressing factors.
BPC-157 appears to improve the rate of collagen reformation following surgery, initially outperforming platelet-growth factor after four days, but eventually becoming equipotent after eight days [8].
In effect, research indicates that BPC-157 can assist tendon regenesis after surgical damage. The peptide has also been delivered via multiple pathways, suggesting that the peptide has a therapeutic benefit via a wide range of delivery mechanisms (see figure below).
Figure: Examples of successful administration mechanisms for the delivery of BPC 157; all routes, local and systemic, have been reported to have positive healing outcomes [7]
Skeletal muscle healing
Similarly, peptide injections enhanced muscle healing from animals whose muscles had been cut or crushed. Interestingly, this effect held true when animals were also given corticosteroids (ie., hydrocortisone), which can slow the healing process [9].
This research group concluded that BPC-157 is capable to ameliorate wound healing and muscle contusion injury even in corticosteroid-treated rats.
BPC-157 completely reversed systemic corticosteroid impairment in muscle healing, modulated corticosteroid’s effects, and represents a potentially important peptide therapy.
Research also shows that besides improving functionality in the muscle, BPC-157 also enhanced enzymatic activity by decreasing muscle proteolysis. Essentially this is showing a decrease in skeletal muscle degradation [10].
The authors concluded that BPC-157 accelerated post-injury skeletal muscle healing in addition to restoring full muscle function that is similar to the finding in tendons.
In addition to muscle injuries caused by direct trauma, there have been several studies that have indicated that BPC-157 may have the ability to recover systemic muscular disturbances in response to induced nervous, electrolyte disturbances and/or
skeletal muscle wasting [11].
Since systemic muscle pain is attributed to infection, autoimmune conditions, illness or side effects from medication, they are considered to be more serious than stress or exercise-related muscle injuries.
Limitations of current research
Although the use of rodents and small mammals being conventional in research, in particular for the development of novel therapeutic agents, caution should be practiced when extrapolating research data to clinical applications.
Notwithstanding the impressive results that have been published to date, there is still a requirement for successful human trials to be completed prior to clinical translation. Since there are obvious differences between rodent and human physiology, it cannot be ignored that this may have a significant impact on the efficacy and safety of (any) novel agents.
However, it is important to realize that BPC-157 is a peptide derived from human gastric juices, therefore, some level of safety in human subjects can be assumed.
However, this still cannot be taken as fact, therefore, due diligence should be done to elucidate whether the reported benefits of BPC-157 extend beyond research animals.
To date, research that utilized BPC-157 as a treatment therapy have demonstrated extremely positive healing effects for various injury types in several soft tissues.
However, at present, studies are predominantly limited to small animal models (predominantly rodents) and the efficacy of BPC-157 is yet to be confirmed in human subjects.
Although further research is required in order to better understand its mechanisms and efficacy in practical settings, BPC-157 has the capability to be developed as a new therapy to conservatively treat or aid recovery following surgery in typically low vascular and low cellular soft tissues such as tendon and ligament tissue.
References:
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2. Bodis, B., et al., Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound, BPC) and their specificity to gastric mucosal cells. Life Sci, 1997. 61(16): p. PL 243-8.
3. Chang, C.H., et al., Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules, 2014. 19(11): p. 19066-77.
4. Krivic, A., et al., Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflamm Res, 2008. 57(5): p. 205-10.
5. Staresinic, M., et al., Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res, 2003. 21(6): p. 976-83.
6. Sikiric, P., et al., Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Curr Pharm Des, 2011. 17(16): p. 1612-32.
7. Gwyer, D., N.M. Wragg, and S.L. Wilson, Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res, 2019. 377(2): p. 153-159.
8. Tkalcevic, V.I., et al., Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol, 2007. 570(1-3): p. 212-21.
9. Pevec, D., et al., Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Med Sci Monit, 2010. 16(3): p. BR81-88.
10. Farges, M.C., et al., Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis. Am J Physiol Endocrinol Metab, 2002. 282(2): p. E326-35.
11. Kang, E.A., et al., BPC157 as Potential Agent Rescuing from Cancer Cachexia. Curr Pharm Des, 2018. 24(18): p. 1947-1956
