PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis

Tendon injury is one of the most serious orthopedic diseases often leading to disability of patients. Major shortages of tendon healing are due to its multiple comorbidities, uncertainty of therapeutic efficacy and insufficient of angiogenesis. With a deeper understanding of angiogenic mechanism of tendon healing, we investigated an innovative microneedle patch loaded with platelet derived growth factor (PDGF) to achieve a constant systemic administration of PDGF to enhance topical tendon healing. Rat achilles tendon injury model was performed as in vivo animal models. Histological staining showed an enhancement of tendon healing quality, especially angiogenesis. Biomechanical studies demonstrated an increase of tendon stiffness, maximum load and maximum stress with treatment of PDGF-loaded microneedles. Furthermore, MAPK/p38/Cyclin D1 pathway and angiogenesis were found to play an important role in tendon healing process by using a biological high throughput RNA-sequence method and bioinformatic analysis. The high throughput RNA-seq tendon healing results were confirmed by histochemical staining and western blot. These results suggest the novel therapeutic potential of PDGF-loaded microneedle patch in tendon surgery.