Research Applications
Tendon and Ligament Healing
BPC-157 has demonstrated significant efficacy in accelerating tendon and ligament repair in multiple animal models. Studies on transected rat Achilles tendon show that BPC-157 treatment accelerates healing by promoting tendon fibroblast outgrowth from tendon explants and markedly increasing the migration potential of cultured tendon fibroblasts. The peptide activates the FAK-paxillin signaling pathway, which is essential for cell migration and tissue reorganization during repair processes. Research indicates BPC-157 significantly enhances cell survival under oxidative stress conditions (H2O2 exposure), protecting fibroblasts during the inflammatory phase of healing when reactive oxygen species are elevated.
BPC-157 upregulates growth hormone receptor expression in tendon fibroblasts at both mRNA and protein levels in a dose- and time-dependent manner. This upregulation persists for up to three days after treatment, with the combination of BPC-157 and growth hormone synergistically enhancing cell proliferation and PCNA expression. The activation of JAK2 phosphorylation downstream of growth hormone receptor signaling provides an additional mechanism for the peptide's healing effects, potentially allowing for reduced growth hormone dosing in therapeutic applications.
In medial collateral ligament (MCL) injury models, BPC-157 administered intraperitoneally (10 μg or 10 ng/kg once daily), topically as a cream layer, or orally in drinking water consistently produced functional, biomechanical, macroscopic, and histological healing improvements throughout the 90-day study period. The peptide proved effective across multiple delivery routes, demonstrating therapeutic flexibility. Biomechanical testing revealed increased load to failure in BPC-157-treated tendons, with significantly higher Achilles Functional Index scores indicating restoration of normal gait and weight-bearing function.
Studies examining early functional recovery show that BPC-157 modulates the healing timeline by accelerating early collagen organization and promoting appropriate scar tissue formation. The peptide demonstrates efficacy even when healing is compromised by concurrent corticosteroid administration, a significant advantage given that corticosteroids are commonly prescribed anti-inflammatory medications that typically impair tissue repair. BPC-157 completely reversed the deleterious effects of systemic methylprednisolone on ligament healing, suggesting protective mechanisms that maintain healing capacity despite anti-inflammatory suppression.
Sources:
- Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol. 2011;110(3):774-780. https://journals.physiology.org/doi/full/10.1152/japplphysiol.00945.2010
- Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014;19(11):19066-19077. https://pmc.ncbi.nlm.nih.gov/articles/PMC6271067/
- Cerovecki T, Bojanic I, Brcic L, et al. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. J Orthop Res. 2010;28(9):1155-1161. https://onlinelibrary.wiley.com/doi/abs/10.1002/jor.21107
- Gwyer D, Wragg NM, Wilson SL. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res. 2019;377(2):153-159. https://link.springer.com/article/10.1007/s00441-019-03016-8
Muscle Injury and Repair
BPC-157 exhibits potent muscle-protective and regenerative properties across various injury models. In crushed gastrocnemius muscle studies, BPC-157 administered either intraperitoneally or locally as a topical cream improved muscle healing macroscopically (reduced hematoma and edema, prevention of post-injury leg contracture), microscopically, and functionally. The peptide normalized enzyme markers of muscle damage including creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase, indicating restoration of muscle cell membrane integrity and metabolic function.
Following transected quadriceps muscle injury, BPC-157 promotes complete functional recovery by stimulating myogenesis through release of specific growth factors that contribute to injured myofibril regeneration. The peptide accelerates early collagen organization and stimulates expression of the EGR-1 gene along with its repressor NAB2, creating a regulatory feedback loop that prevents excessive fibrosis while promoting organized tissue remodeling. This balanced response results in functional muscle restoration rather than scar tissue formation that would compromise contractile capacity.
BPC-157 demonstrates remarkable efficacy in muscle-to-bone reattachment following complete detachment of the quadriceps muscle from its attachments. In control animals, surgical detachment resulted in definitive healing failure with impaired walking and permanent knee flexure persisting through 90-day follow-up. BPC-157 therapy initiated immediately post-injury produced consistent healing effects at all time points, as confirmed by macroscopic/microscopic assessment, ultrasound, magnetic resonance imaging, biomechanical testing, and functional evaluation. The peptide stimulated reattachment fiber formation from both the muscle end and the bone surface, with periosteum reactivation evident by day 3 post-detachment. At 3 months, BPC-157-treated animals exhibited well-organized newly formed bone with muscle fibers oriented parallel to the bone axis and in close contact with the bone surface, restoring the musculoskeletal junction.
Research on muscle contusions shows BPC-157 more rapidly and effectively stimulates tissue repair compared to standard anti-inflammatory treatments. The peptide reduces inflammatory cell infiltration while simultaneously promoting angiogenesis and collagen synthesis, creating an optimal healing environment. In models of corticosteroid-impaired muscle healing, BPC-157 completely reverses the aggravating effects of systemic corticosteroid treatment (6α-methylprednisolone), restoring normal healing kinetics and full functional recovery.
Sources:
- Novinscak T, Brcic L, Staresinic M, et al. Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat. Surg Today. 2008;38(8):716-725. https://pubmed.ncbi.nlm.nih.gov/18668315/
- Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res. 2006;24(5):1109-1117. https://pubmed.ncbi.nlm.nih.gov/16609978/
- Pevec D, Novinscak T, Brcic L, et al. Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Med Sci Monit. 2010;16(3):BR81-88. https://pubmed.ncbi.nlm.nih.gov/20190676/
- Lovric-Kojundzic I, Demarovic M, Boban M, et al. Stable Gastric Pentadecapeptide BPC 157 as Therapy After Surgical Detachment of the Quadriceps Muscle from Its Attachments for Muscle-to-Bone Reattachment in Rats. Pharmaceutics. 2025;17(1):119. https://www.mdpi.com/1999-4923/17/1/119
Bone Healing and Regeneration
BPC-157 significantly accelerates bone healing in segmental osteoperiosteal defect models. In rabbit studies with 0.8 cm radial bone defects that remained incompletely healed in all control animals for 6 weeks, BPC-157 treatment (administered locally into the bone defect or intramuscularly) produced healing comparable to standard treatments including local bone marrow application or autologous cortical bone grafting. Radiographic assessment demonstrated increased callus surface area, with quantitative histomorphometry confirming enhanced bone formation. The peptide's effectiveness when given either continuously (daily) or intermittently (4 applications over 10 days) suggests sustained biological effects beyond the peptide's short plasma half-life.
The osteogenic effect of BPC-157 manifests through multiple mechanisms including stimulation of angiogenesis within bone tissue and enhancement of osteoblast activity. Studies show BPC-157 induces formation of new blood vessels at the fracture site, which is critical for delivering nutrients, oxygen, and osteoprogenitor cells necessary for bone regeneration. Microphotodensitometry analysis reveals improved mineralization patterns in BPC-157-treated bone compared to controls, indicating more mature bone formation rather than fibrous scar tissue.
BPC-157 promotes bone healing under compromised conditions including delayed union, avascular necrosis, and impaired fracture healing scenarios. The peptide's ability to activate VEGFR2-nitric oxide signaling in bone tissue enhances bone matrix deposition and fracture consolidation. Research demonstrates BPC-157 increases mesenchymal cell recruitment with periosteum reactivation occurring within 3 days of treatment initiation, establishing conditions favorable for rapid bone repair.
The peptide exhibits efficacy across various administration routes including local application at the injury site, systemic intramuscular injection, and oral delivery. This flexibility allows for optimization of treatment protocols based on injury location and severity. Importantly, BPC-157 demonstrates no interference with normal bone remodeling processes, maintaining the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption necessary for proper structural regeneration.
Sources:
- Sebecic B, Nikolic V, Sikiric P, et al. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. Bone. 1999;24(3):195-202. https://pubmed.ncbi.nlm.nih.gov/10071911/
- Seiwerth S, Rucman R, Turkovic B, et al. BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing. Curr Pharm Des. 2018;24(18):1972-1989. https://pubmed.ncbi.nlm.nih.gov/29998800/
- Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review. HSS J. 2025 (Online ahead of print). https://pmc.ncbi.nlm.nih.gov/articles/PMC12313605/
Gastrointestinal Healing and Protection
BPC-157 demonstrates comprehensive protective and healing effects throughout the entire gastrointestinal tract from the esophagus to the colon. The peptide exhibits consistent efficacy in models of acute and chronic injury regardless of administration route (intraperitoneal, oral, or local application), a unique characteristic distinguishing it from other growth factors that typically require localized delivery with carrier systems. Clinical trials in inflammatory bowel disease (Phase II) have shown BPC-157 to be safe with no reported adverse effects or toxicity.
In esophageal injury models, BPC-157 normalizes sphincter function by increasing pressure in both the lower esophageal sphincter (LES) and pyloric sphincter (PS) in animals with sphincter dysfunction, while in healthy animals the peptide demonstrates adaptive effects that maintain physiological sphincter tone. This modulatory capacity allows BPC-157 to correct both hypo- and hypermotility conditions. Studies on esophagitis demonstrate marked reduction in inflammatory damage with BPC-157 treatment, protecting the esophageal mucosa from acid and bile reflux injury.
Research on gastric and duodenal ulcers shows BPC-157 accelerates ulcer healing through multiple mechanisms including enhanced mucosal cell proliferation, increased mucus production, and improved blood flow to the injured area. The peptide protects gastric mucosa from damage induced by NSAIDs (non-steroidal anti-inflammatory drugs), alcohol, and stress, counteracting the pathological effects of these ulcerogenic agents. BPC-157 reverses NSAID-induced intestinal lesions by promoting mucosal regeneration through angiogenesis and epithelial cell migration.
In inflammatory bowel disease models including ulcerative colitis and cysteamine-induced colitis, BPC-157 reduces inflammatory markers (IL-6, TNF-α, IL-1β), improves mucosal architecture, and accelerates healing of damaged intestinal tissue. The peptide successfully heals internal fistulas (gastrocutaneous, duodenocutaneous, and colocutaneous) in experimental models, achieving fistula closure even when treatment is delayed for one month after fistula formation. Healing occurs through restoration of both the intestinal and cutaneous defects, with biomechanical testing confirming the treated areas can withstand normal physiological pressures without leakage.
BPC-157 reverses short bowel syndrome manifestations in animal models, promoting constant weight gain above preoperative values and increasing villus height, crypt depth, and muscle layer thickness in the remaining intestinal tissue. This adaptive response suggests the peptide stimulates compensatory intestinal hypertrophy and improved absorptive capacity. Studies on intestinal anastomosis (surgical reconnection of bowel segments) demonstrate BPC-157 significantly enhances anastomotic healing strength and reduces the incidence of dehiscence (anastomotic breakdown), a serious surgical complication with high morbidity and mortality rates.
The peptide's effects on the gastrointestinal tract involve interaction with the nitric oxide system, providing endothelium protection and angiogenic effects even in severely compromised conditions. BPC-157 stimulates expression of EGR-1 gene responsible for cytokine and growth factor generation and early collagen formation, while also inducing NAB2 expression to regulate the extent of tissue response. These coordinated molecular effects result in organized tissue repair rather than dysregulated scarring.
Sources:
- Sikiric P, Seiwerth S, Rucman R, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Curr Pharm Des. 2011;17(16):1612-1632. https://pubmed.ncbi.nlm.nih.gov/21548867/
- Sikiric P, Hahm KB, Blagaic AB, et al. Stable gastric 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. 2006;100(5):465-469. https://pubmed.ncbi.nlm.nih.gov/16799259/
- Sikiric P, Seiwerth S, Brcic L, et al. Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights. World J Gastroenterol. 2017;23(48):8465-8488. https://pmc.ncbi.nlm.nih.gov/articles/PMC5752708/
- Sikiric P, Rucman R, Turkovic B, et al. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem. 2012;19(1):126-132. https://pubmed.ncbi.nlm.nih.gov/22300085/
Vascular and Angiogenic Effects
BPC-157 functions as a potent angiomodulatory agent, optimizing vascular responses across diverse injury contexts. The peptide promotes angiogenesis—the formation of new blood vessels from existing vasculature—through activation of the VEGFR2-Akt-eNOS signaling pathway. Research using chicken chorioallantoic membrane (CAM) assays and endothelial tube formation assays demonstrates BPC-157 significantly increases vessel density both in vivo and in vitro. In hindlimb ischemia models, the peptide accelerates blood flow recovery as measured by laser Doppler scanning, with histological analysis confirming increased vessel numbers and enhanced vascular expression of VEGFR2.
BPC-157 upregulates VEGFR2 expression in vascular endothelial cells at both mRNA and protein levels without increasing VEGF-A production, suggesting the peptide sensitizes endothelial cells to existing VEGF rather than simply increasing ligand availability. The peptide promotes VEGFR2 internalization through dynamin-dependent endocytosis, a process essential for sustained receptor signaling. Inhibition of endocytosis with dynasore blocks BPC-157-induced VEGFR2 activation, demonstrating the importance of receptor trafficking in the peptide's angiogenic mechanism.
The peptide activates endothelial nitric oxide synthase (eNOS) through both VEGFR2-dependent and VEGFR2-independent pathways. The VEGFR2-independent mechanism involves Src kinase-mediated phosphorylation of caveolin-1, disrupting the inhibitory interaction between caveolin-1 and eNOS. This dual activation mechanism provides redundancy ensuring robust nitric oxide production for vasodilation and vascular protection. BPC-157 demonstrates a distinctive modulatory effect on nitric oxide levels, increasing or decreasing NO production as needed to maintain vascular homeostasis, always combined with counteraction of free radical formation.
Studies on vascular injury demonstrate BPC-157 protects endothelium from damage, prevents thrombosis formation, and promotes vessel healing. In abdominal aorta anastomosis models, the peptide prevents and reverses thrombus formation, suggesting antithrombotic effects mediated through endothelial protection and normalized coagulation cascade activity. BPC-157 rapidly activates collateral blood vessels to bypass vascular obstructions, as demonstrated in colonic ischemia models where the peptide restored blood flow around ligated vessels within minutes to hours of administration.
The peptide modulates vasomotor tone in an endothelium- and nitric oxide-dependent manner. In ex vivo studies using isolated blood vessels, BPC-157 induces vasodilation through increased nitric oxide production, with effects blocked by endothelium removal or eNOS inhibition. The peptide has demonstrated efficacy in normalizing pathological blood pressure states, reversing hypertension induced by NOS inhibitors and attenuating hypotension induced by excessive NO substrate administration, indicating adaptive vascular regulation.
Research on angiogenesis in healing tissues shows BPC-157 increases VEGF, CD34, and factor VIII (FVIII) positive vascular elements in injured muscle and tendon. The angiogenic response is augmented and temporally shifted toward earlier vessel formation, providing oxygen and nutrients to regenerating tissue during critical early healing phases. Importantly, BPC-157 shows no direct angiogenic effect on endothelial cell cultures, suggesting its pro-angiogenic activity requires the context of injury and healing responses present in vivo—a safety feature that may limit unwanted neovascularization in healthy tissues.
Sources:
- Hsieh MJ, Liu HT, Wang CN, et al. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med. 2017;95(3):323-333. https://pubmed.ncbi.nlm.nih.gov/27847966/
- Hsieh MJ, Tsai TL, Hsieh YH, Huang CY, Wang CJ, Hsu YH. Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Sci Rep. 2020;10:17078. https://www.nature.com/articles/s41598-020-74022-y
- Seiwerth S, Brcic L, Vuletic LB, et al. BPC 157 and blood vessels. Curr Pharm Des. 2014;20(7):1121-1125. https://pubmed.ncbi.nlm.nih.gov/23782145/
- Brcic L, Brcic I, Staresinic M, et al. Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing. J Physiol Pharmacol. 2009;60(Suppl 7):191-196. https://pubmed.ncbi.nlm.nih.gov/20388964/
