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Peptides for Tendon Repair Research

01dragonslayer

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Tendon injuries are incredibly common, not just among athletes, but in the general population. Commonly injured tendons include the Achilles and biceps tendon as well as tendons of the hands and feet. Unlike most illnesses and injuries, however, tendon injuries are more common among the young than the old. This is counterintuitive, especially given that the cause of these injuries is cumulative degeneration followed by sudden excess loading. Few of tendon injuries are caused by systemic disease or a genetic disorder.

The incidence of tendon-related injuries is on the rise, increasing almost 140% between 2012 and 2016[1]. The increase is attributed to greater amateur athletic participation, but also has roots in high rates of on-the-job injuries. For these reasons, and many others, peptides for tendon repair research have become a hot topic. Here is a look at what the state of the art is in the field of peptides for tendon repair research.



How Do Tendons Heal?​

Tendons connect muscle to bone and transfer all the energy from a muscle contraction to the bones that provide structure and support. Unfortunately, tendons can be cut, bruised, sprained, or ruptured in a variety of ways. Tendon ruptures are serious and can take anywhere from four to eighteen months to heal and almost always require surgery. Even tendonitis, which is just inflammation due to minor damage, can take upwards of four months to heal.

Unfortunately, injured tendons are at higher risk of re-injury, generally because the healing process is not as orderly as when a tendon is originally formed. Tendons are not designed to regenerate, but rather are meant to last a lifetime without much change. As such, they do not possess the kind of regenerative properties (e.g., abundant stem cells) that tissues like the GI tract or skin do. What is worse, the rate at which a tendon can heal, even if the healing is limited, is almost always outpaced by the rate at which we can cause injury to it. In other words, tendon injury tends to accumulate and the more active you are, the more likely you are to experience a large-scale tendon failure.

Under the healing process, tendons first become inflamed, an immune response that causes pain and limits mobility. This stage, however, is slow to resolve because of the tendon’s poor blood supply. Eventually, however, healing gives way to the repair phase in which cells like fibroblasts proliferate and start replacing damaged tissue. This stage then gives way to remodeling, which is carried out by stem cells and various other cells. Once again, the relative dearth of nutrient supply to the tendon limits the effectiveness of these stages and accounts for the very slow rate at which tendons heal.



Why Don’t Tendons Heal Well?​

The reasons that tendons do not heal properly are several-fold. First, as discussed, the blood-supply to tendons is more limited than it is to other tissues. This limits the number of fibroblasts and other repair cells that can reach the site of injury. With fewer cells to do the work, tendons heal slowly and often incompletely.

Another reason that tendons do not heal well is that the longer an injury takes to repair, the more stress the tissue is subjected to during the healing process. These stresses tend to cause misalignment of the collagen and elastin fibers of the extracellular matrix, leading to a kind of scar that is more than merely cosmetic. Tendons, with their poor blood supply, are one of the slowest tissues to heal following injury. This makes them susceptible to further injury that results in misaligned extracellular matrix fibers. These fibers do not efficiently transfer forces and aren’t properly aligned with the direction of maximal force application. This causes scarred tendons to be more prone to re-injury.

Research shows that tendons do not change throughout our adult lives. They are designed to last a lifetime and thus have very few in-built mechanisms for repair. Unlike bone, tendons are not constantly remodeled and repaired in response to stress. Thus, our tendons do not change as quickly as our muscles and bones do, putting them at higher risk of injury. Then, when they are injured, tendons don’t heal very quickly without a boost[2].

Fortunately, research has revealed that some peptides can help to boost tendon repairs. Research into these peptides is helping to reveal not only how to accelerate tendon healing rates, but how to make the result more robust. Tendons in the experimental groups of these research studies tend to be stronger and more resilient than those that are not exposed to peptides during the healing process. Here is a look at some of the peptides for tendon repair research and what they are teaching us about how to heal tendons faster and ensure that the results are stronger.



BPC 157​

BPC 157 is a derivative of body protection compound, a natural peptide found in the GI tract of most mammals including humans. BPC 157 has been shown to boost blood vessel growth, regulate the coagulation cascade, increase nitric oxide generation, and alter immune system function.

BPC 157 has special application in tendons because of its ability to increase recruitment of fibroblasts. Fibroblasts are the cells that produce collage and elastin. They play important roles not only in the speed of injury repair, but in the formation of scar tissue as well. BPC 157 has been shown to increase how quickly fibroblasts proliferate and migrate to the se site of injury[3], [4]. Research also shows that BPC 157 enhances fibroblast function in musculoskeletal tissue by enhancing the expression of growth hormone receptors within fibroblasts[5].

Another reason that BPC 157 is beneficial in tendon injury is that it increases blood vessel growth to areas of injury[6], [7]. This provides for increased delivery of cells, nutrients, and raw materials necessary for wound repair. Experiments looking directly at the role of BPC 157 in tendon repair reveal that the peptide is more effective than a number of natural growth hormones in promoting tendon healing[8].

BPC 157 does not just accelerate rates of healing though; it increases the quality of tendon healing. In rat models, administration of BPC 157 improves functional and biomechanical properties of repaired tendons, indicating that they are stronger than those that heal without BPC 157. Histological reviews of the structure of the tendons treated with BPC 157 show superior fiber alignment and thus confirm that the tendons are structurally superior to those that were not exposed to BPC 157. In practical terms, this improved healing manifests as preserved muscle motor function, preserved walking patterns, and lack of joint contracture[9].



Growth Hormone Modulating Peptides​

Growth hormone has long been known to stimulate the synthesis of collagen in connective tissue. It is also a general growth factor and immune modulator, helping to boost blood vessel growth and regulating the migration and proliferation of cells like fibroblasts. In fact, research shows that exogenous growth hormone administration can increase tendon collagen synthesis by nearly 4-fold[10].

Unfortunately, direct administration of growth hormone is fraught with problems and side effects. These drawbacks make it generally unsuitable for the treatment of tendon injuries. Fortunately, there are peptides that can stimulate growth hormone release in a more natural way and help researchers avoid the side effects of direct growth hormone administration. These peptides are divided two general classes. The first are the growth hormone releasing hormone analogues like Sermorelin, mod GRF, and CJC 1295. These peptides help to preserve normal growth hormone release patterns and have several beneficial attributes.

The second class of growth hormone increasing peptides are the growth hormone secretagogue receptor agonists. These peptides include ipamorelin, GHRP-2, and GHRP-6. They are well known for their ability to vastly increase growth hormone levels. Many of these peptides also possess specific additional effects that make them useful in various settings. Ipamorelin, for instance, has strong positive effects on bone growth and strength, making it useful in the setting of osteoporosis or concomitant bone fractures.

The combination of growth hormone enhancing peptides and BPC 157 has not been extensively tested. The combination would likely be synergistic since BPC 157 enhances the actions of growth hormone on fibroblasts and on cells of the immune system.



IGF-1-LR3​

Modified, synthetic versions of IGF-1 are available for research. IGF-1-LR3, for instance, has many of the same properties as IGF-1 but its prolonged half-life in the bloodstream makes it more suitable for research. In connective tissues, IGF-1-LR3 promotes cell division and proliferation as much as 3-fold over baseline. This leads to faster tissue repair. The peptide has also been looked at for its ability to extend longevity and enhance muscle growth.



Thymosin Beta-4 (TB-4) and TB-500​

TB-500 is a derivative of Thymosin Beta-4, so everything discussed in this section applies to both peptides. Thymosin Beta-4 is the naturally occurring compound found in many living organisms. It has long been associated with healing and has been extensively used in peptides for tendon repair research.

Research shows that TB-500 is very similar to BPC 157 in many respects. It increases blood vessel growth, improves cell migration, decreases inflammation, promotes extracellular matrix production, and generally increases rates of wound healing[11]. There is good reason to believe that TB-500 and BPC 157 would work together, perhaps synergistically, to improve tendon repair. Scientists have developed a gel, infused with TB-500, that could potentially be injected into tendons, joints, and other areas of injury to help speed up healing[12]. The gel may even be useful as a preventative in individuals at high risk of degenerative damage like osteoarthritis or Achilles tendon rupture.



Peptides for Tendon Research: Summary​

Tendons are designed to last a lifetime, a feature that makes them very difficult to repair when they are damaged. Even surgical repair of tendons is often less than optimal because the structure of the tendon is never quite as strong as it was originally. Additionally, the healing process takes so long that people often subject the tendon to additional damage, simply as a result of normal use, that limits its final strength. Peptides for tendon research are offering some hope, however, that tendon repair can be jump started by recruiting cells and chemical messengers that speed up the healing process and make it more efficient. With continued research, scientists hope to unlock the right combination and sequence of peptides to allow tendons to heal quickly and with greater strength. Stronger tendons mean improved functionality following injury and improved functionality means a higher quality of life, decreased risk of re-injury, and decreased risk of subsequent injury (e.g., trips and falls) as a result of weakened tendons.
 
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