Peptides For Healing | Ultimate Guide In 2023

Peptides are short chains of amino acids, typically consisting of fewer than 50 amino acid residues. Due to their small size and based on their specific amino acid sequences, peptides can interact with certain receptors in the body to influence various physiological processes. For instance, peptides play important roles in the body's natural signaling pathways and regulatory systems. They can act as signaling molecules, neurotransmitters, hormones, or enzyme inhibitors, among other functions. Their ability to interact with specific receptors or molecules allows them to exert precise and targeted effects, to learn more about healing peptides visit Peptide Sciences .  

In recent years, peptides have gained attention due to their potential applications in treating various conditions. Peptides for recovery, peptides for tendon repair, peptides for injury, and peptides for muscle repair have all been developed and tested in animal models. They offer advantages such as high specificity, low toxicity, and the ability to mimic natural biological processes. Peptides can be produced synthetically and designed or modified to enhance their stability, bioavailability, and target selectivity. This makes peptides particularly convenient to work with. Peptides have been investigated for a wide range of therapeutic applications, including 

• Regulation of hormone levels: Peptides can act as hormone analogs or modulators, influencing hormone production, release, or activity. For example, insulin and glucagon-like peptide-1 (GLP-1) are peptide hormones involved in blood sugar regulation. 
• Modulation of immune responses: Certain peptides can interact with immune cells, modulating immune responses such as inflammation or immune cell activation. This potential immunomodulatory effect has been investigated for conditions like autoimmune diseases and cancer. 
• Antimicrobial activity: Some peptides exhibit antimicrobial properties and can kill or inhibit the growth of bacteria, viruses, fungi, or other pathogens. These peptides, known as antimicrobial peptides (AMPs), have attracted attention as potential alternatives to conventional antibiotics. 
• Pain management: Certain peptides can act on pain receptors or neurotransmitters involved in pain signaling, providing potential applications in pain management or the development of analgesics. 
• Tissue repair and regeneration: Peptides that promote cell proliferation, migration, or tissue remodeling have been studied for their potential in wound healing, tissue regeneration, and tissue engineering.

Several peptides have stood out from the rest for their potential benefits in wound healing, tissue repair, and regeneration. These best healing peptides include BPC-157, Thymosin Beta-4/TB500, Melanotan 2 (II), Sermorelin, and GHK-Cu. 

BPC-157 (Body Protective Compound-157) 

BPC-157 is a synthetic peptide derived from a protein in gastric juice. It has shown promising effects in promoting tissue repair and healing in various animal models, including muscle, tendon, and gastrointestinal tissues. BPC-157 is believed to exert its effects through multiple mechanisms, including promoting blood vessel formation, reducing inflammation, and enhancing cell migration and proliferation. 

BPC 157 has shown very promising effects in promoting the healing of tendons, particularly in animal models. Tendons are known for their slow and challenging healing process, and BPC 157 has demonstrated the ability to accelerate tendon growth by enhancing fibroblast outgrowth, survival, and migration in mouse models[1]. These features make BPC 157 one of the best peptides for tendon repair. 

In addition to accelerating healing rates, BPC 157 has been found to improve the quality of tendon healing. In rat models, it has been shown to enhance functional and biomechanical properties of repaired tendons, leading to preserved muscle motor function, walking pattern, and lack of joint contracture. These improvements are reflected in the histological structure of the tendons[2], [3]. 

The mechanism by which BPC 157 promotes tendon repair is believed to involve enhancing fibroblast function by increasing the expression of growth hormone receptors within fibroblasts. Growth hormone supplementation is known to improve musculoskeletal development and repair, but it can have off-target effects. BPC 157, on the other hand, appears to avoid these off-target effects. 

While most of the studies on BPC 157 have been conducted in animal models, it is worth reiterating that BPC 157 is a naturally occurring peptide found in human gastric contents. Despite its potential therapeutic benefits, limited research has been conducted in humans. Though BPC 157 has not been specifically tested in humans for soft tissue repair, it has undergone Phase I human clinical trials as a potential therapy for inflammatory bowel disease. These trials have shown that BPC 157 is safe and effective in that context, making it a very promising peptide for tendon repair[4]–[6]. 

Thymosin Beta-4/TB500 

Thymosin Beta-4 is a naturally occurring peptide involved in various cellular processes, including wound healing and tissue repair. Its synthetic analogue, TB500, has similar though slightly more limited properties. The terms are often used interchangeably, even though Thymosin Beta-4 is 43 amino acids in length while TB500 is just seven amino acids long. Both have been shown to promote angiogenesis (formation of new blood vessels), enhance migration of cells to the site of injury, and modulate inflammation. Thymosin Beta-4 has been studied in preclinical and clinical settings for its potential therapeutic applications in wound healing, corneal repair, and cardiac regeneration. Here are some key points regarding its effects and research findings: 

Angiogenesis: Thymosin Beta-4 has been shown to promote the formation of new blood vessels (angiogenesis) in injured tissues. This is important for delivering oxygen and nutrients to the site of injury, facilitating tissue repair and making Thymosin Beta-4 one of the best healing peptides[7]. 

Cell migration: Thymosin Beta-4 enhances the migration of cells, including endothelial cells and fibroblasts, to the site of injury. This promotes the formation of granulation tissue, which is crucial for wound healing. 

Anti-inflammatory effects: Thymosin Beta-4 has been found to modulate the inflammatory response by reducing pro-inflammatory cytokines and promoting the production of anti-inflammatory molecules. This helps to create an environment conducive to healing and tissue repair. 

Wound healing and tissue repair: Preclinical studies have demonstrated that Thymosin Beta-4 accelerates wound healing in various models, including skin wounds, corneal injuries, and muscle injuries. It has been shown to enhance the regenerative capacity of tissues and improve the structural and functional properties of healed tissue. 

Corneal repair: Thymosin Beta-4 has shown promise in promoting corneal repair and regeneration. It has been studied for its potential application in treating corneal injuries, corneal ulcers, and corneal dystrophies. 

Cardiac regeneration: Research has also explored the potential of Thymosin Beta-4 in cardiac regeneration. Studies in animal models and small clinical trials have suggested that Thymosin Beta-4 may have beneficial effects in promoting cardiac tissue repair and improving heart function after a heart attack[8], [9]. 

Melanotan II 

Melanotan II is a synthetic peptide that, though it is not traditionally thought of as a peptide for recovery, has in fact been investigated for its potential wound healing properties. It has been shown to enhance wound closure and reduce inflammation in animal models. Melanotan II also has melanotropic effects, which means it can stimulate skin pigmentation, and it has been explored for potential use in treating conditions like vitiligo. 

The activation of pro-opiomelanocortin (POMC)-derived neuropeptides has shown potential in rescuing synaptic dysfunction caused by neurofibrillary tangles, a hallmark feature of Alzheimer's Disease. POMC-derived neuropeptides can be activated by melanocortin receptors, and studies conducted in mouse models have explored the use of melanotan 2 in this context. 

Research in these mouse models has demonstrated that melanotan 2 can significantly reduce amyloid accumulation, which is another pathological feature of Alzheimer's Disease. Additionally, it has been found to prominently reduce the presence of A1 subtype reactive astrocytes. A1 astrocytes are believed to play a role in neurotoxicity and neuronal death in Alzheimer's Disease. Therefore, the reduction of A1 astrocytes suggests that melanotan 2 may have a beneficial impact on neurotoxicity in this disease. 

These findings indicate that melanocortin activation could be a potential therapeutic target in the treatment of Alzheimer's Disease. This novel pathway provides an avenue for investigating new approaches for Alzheimer's treatment and may also hold promise for mitigating neurotoxicity in other degenerative brain diseases. 

GHK-Cu 

GHK-Cu is a peptide that consists of the amino acids glycine, histidine, and lysine, with copper bound to it. It has shown promise in promoting wound healing, reducing inflammation, and stimulating the synthesis of collagen and other extracellular matrix components. GHK-Cu is believed to modulate various cellular processes involved in tissue repair and regeneration and is amongst the most researched peptides for muscle repair. 

In skin cultures, GHK has been found to stimulate the synthesis and breakdown of various components of the extracellular matrix, including collagen, glycosaminoglycans, proteoglycans, and chondroitin sulfate. This effect is partly mediated by the recruitment of fibroblasts, immune cells, and endothelial cells to the site of injury, coordinating their activity in repairing damaged skin[10]–[12]. 

Studies conducted in mice have demonstrated that GHK-Cu can increase the rate of healing in burn injuries by up to 33%[12]. In addition to recruiting immune cells and fibroblasts, GHK-Cu promotes blood vessel growth, which is crucial in burn wound healing as burned skin often has impaired blood vessel regeneration. These findings open up new possibilities for improving wound care in burn units and accelerating the healing process. 

Bacterial and fungal infections can significantly impede the healing process of wounds, particularly in individuals with compromised immune systems or burn injuries. In this context, GHK-Cu has demonstrated antimicrobial properties when combined with specific fatty acids to create a compound that effectively slows the growth of various bacteria and fungi[13]. 

In the treatment of diabetic ulcers, research has shown that GHK-Cu, when used in conjunction with standard care regimens, yields superior results compared to standard care alone. Diabetic patients receiving both GHK-Cu and standard care exhibited approximately a 40% increase in wound closure and a 27% reduction in infection rates when compared to control groups[14], [15]. Similar positive outcomes were observed in patients with ischemic open wounds, further supporting the beneficial effects of GHK-Cu in promoting wound healing and reducing the risk of infection. 

LL-37 

LL-37 is an antimicrobial peptide that is naturally produced by immune cells, including neutrophils and macrophages. It is known for its broad-spectrum antimicrobial activity against various types of bacteria, fungi, and viruses. Its myriad properties make LL-37 an excellent peptide for recovery from a variety of injuries, from trauma to diabetic ulcers, that are contaminated by pathogens. 

LL-37 exhibits several mechanisms of action that contribute to its antimicrobial properties. It can directly disrupt the membranes of microbial cells, leading to their destruction. Additionally, LL-37 can modulate the immune response by attracting immune cells to the site of infection, promoting the clearance of pathogens, and regulating the inflammatory process[16], [17]. 

In addition to its antimicrobial effects, LL-37 has been found to have wound healing properties. It can accelerate the wound healing process by promoting the migration and proliferation of skin cells, such as keratinocytes and fibroblasts. LL-37 also stimulates the production of growth factors and extracellular matrix components, which are essential for tissue repair and regeneration[18]. 

Due to its dual antimicrobial and wound healing properties, LL-37 has garnered attention as a potential therapeutic agent for the treatment of infected wounds and chronic ulcers. Research studies and preclinical trials have shown promising results regarding its effectiveness in enhancing wound healing and reducing microbial burden in various types of wounds. 

Sermorelin 

Sermorelin has shown beneficial effects on tissue regeneration, scar formation, inflammation, and infection risk following injury[19]. When administered after an injury, sermorelin has been found to improve tissue health and promote wound repair by reducing inflammation and shifting cytokine production. As a stimulator of GH release, sermorelin fits nicely into the group of peptides for muscle repair, but would be equally as suited among peptides for tendon repair or peptides for injury. It is, without a doubt, one of the best healing peptides in animal research trials. 

Increased growth hormone (GH) levels, achieved through sermorelin supplementation, are associated with higher levels of extracellular matrix deposition. The extracellular matrix provides the structural framework for wound repair, including the production of collagen, elastin, and other proteins. Achieving the right balance of extracellular matrix production is crucial for optimal wound healing without excessive scar formation. 

Sermorelin has also been studied in the context of recovery after a heart attack[20]. Scar formation in the heart can lead to complications such as weakness, conduction problems, and heart failure. Research indicates that sermorelin can protect heart cells from cell death, promote new blood vessel growth, and reduce levels of inflammatory cytokines[21]. These effects contribute to a decrease in scar extent and density, improving long-term outcomes following a heart attack. 

Summary of Peptides for Healing 

Peptides can produce healing effects in a number of ways. While some peptides enhance the function of the immune system, others encourage repair processes to operate faster or more efficiently. To date, much animal research has focused on individual peptides and their properties when used alone. Future research would do well to consider if the use of two or several of these peptides, in conjunction, produce synergies in the healing process. 

Resources 

[1] C.-H. Chang, W.-C. Tsai, Y.-H. Hsu, and J.-H. S. Pang, “Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts,” Mol. Basel Switz., vol. 19, no. 11, Art. no. 11, Nov. 2014, doi: 10.3390/molecules191119066. 

[2] D. Gwyer, 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., vol. 377, no. 2, Art. no. 2, Aug. 2019, doi: 10.1007/s00441-019-03016-8. 

[3] T. Cerovecki et al., “Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat,” J. Orthop. Res. Off. Publ. Orthop. Res. Soc., vol. 28, no. 9, Art. no. 9, Sep. 2010, doi: 10.1002/jor.21107. 

[4] A. Duzel et al., “Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights,” World J. Gastroenterol., vol. 23, no. 48, Art. no. 48, Dec. 2017, doi: 10.3748/wjg.v23.i48.8465. 

[5] R. Klicek et al., “Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system,” J. Pharmacol. Sci., vol. 108, no. 1, Art. no. 1, Sep. 2008, doi: 10.1254/jphs.fp0072161. 

[6] “PCO-02 - Safety and Pharmacokinetics Trial - Full Text View - ClinicalTrials.gov,” Jul. 23, 2020. https://clinicaltrials.gov/ct2/show/NCT02637284 (accessed Jul. 23, 2020). 

[7] K. N. Dubé and N. Smart, “Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease,” Expert Opin. Biol. Ther., vol. 18, no. sup1, Art. no. sup1, Jul. 2018, doi: 10.1080/14712598.2018.1459558. 

[8] K. M. Kassem, S. Vaid, H. Peng, S. Sarkar, and N.-E. Rhaleb, “Tβ4-Ac-SDKP pathway: Any relevance for the cardiovascular system?,” Can. J. Physiol. Pharmacol., vol. 97, no. 7, pp. 589–599, Jul. 2019, doi: 10.1139/cjpp-2018-0570. 

[9] A. D. Shaghiera, P. Widiyanti, and H. Yusuf, “Synthesis and Characterization of Injectable Hydrogels with Varying Collagen−Chitosan−Thymosin β4 Composition for Myocardial Infarction Therapy,” J. Funct. Biomater., vol. 9, no. 2, p. E33, Apr. 2018, doi: 10.3390/jfb9020033. 

[10] Y. Dou, A. Lee, L. Zhu, J. Morton, and W. Ladiges, “The potential of GHK as an anti-aging peptide,” Aging Pathobiol. Ther., vol. 2, no. 1, pp. 58–61, Mar. 2020, doi: 10.31491/apt.2020.03.014. 

[11] L. Pickart and A. Margolina, “Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data,” Int. J. Mol. Sci., vol. 19, no. 7, p. 1987, Jul. 2018, doi: 10.3390/ijms19071987. 

[12] X. Wang et al., “GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis,” Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc., vol. 25, no. 2, pp. 270–278, Apr. 2017, doi: 10.1111/wrr.12520. 

[13] M. Kukowska, M. Kukowska-Kaszuba, and K. Dzierzbicka, “In vitro studies of antimicrobial activity of Gly-His-Lys conjugates as potential and promising candidates for therapeutics in skin and tissue infections,” Bioorg. Med. Chem. Lett., vol. 25, no. 3, pp. 542–546, Feb. 2015, doi: 10.1016/j.bmcl.2014.12.029. 

[14] G. D. Mulder et al., “Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper,” Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc., vol. 2, no. 4, Art. no. 4, Oct. 1994, doi: 10.1046/j.1524-475X.1994.20406.x. 

[15] S. O. Canapp et al., “The effect of topical tripeptide-copper complex on healing of ischemic open wounds,” Vet. Surg. VS, vol. 32, no. 6, Art. no. 6, Dec. 2003, doi: 10.1111/j.1532-950x.2003.00515.x. 

[16] J. M. Kahlenberg and M. J. Kaplan, “Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease,” J. Immunol. Baltim. Md 1950, vol. 191, no. 10, p. 10.4049/jimmunol.1302005, Nov. 2013, doi: 10.4049/jimmunol.1302005. 

[17] D. S. Alexandre-Ramos et al., “LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation,” Biomed. Pharmacother. Biomedecine Pharmacother., vol. 108, pp. 1584–1590, Dec. 2018, doi: 10.1016/j.biopha.2018.10.014. 

[18] T. R. Hata and R. L. Gallo, “Antimicrobial Peptides, Skin Infections and Atopic Dermatitis,” Semin. Cutan. Med. Surg., vol. 27, no. 2, pp. 144–150, Jun. 2008, doi: 10.1016/j.sder.2008.04.002. 

[19] L. Recinella et al., “Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice,” Sci. Rep., vol. 10, no. 1, Art. no. 1, Jan. 2020, doi: 10.1038/s41598-019-57292-z. 

[20] R. M. Kanashiro-Takeuchi et al., “New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor,” Oncotarget, vol. 6, no. 12, Art. no. 12, 2015, doi: 10.18632/oncotarget.3303. 

[21] L. L. Bagno et al., “Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy,” J. Am. Heart Assoc., vol. 4, no. 4, p. e001464, Mar. 2015, doi: 10.1161/JAHA.114.001464. 

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