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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006422002265 |
| _version_ | 1798030717642342400 |
|---|---|
| author | Xuanzhe Liu Yuange Li Shuo Wang Mingkuan Lu Jian Zou Zhongmin Shi Binbin Xu Wei Wang Bo Hu Tuo Jin Fei Wu Shen Liu Cunyi Fan |
| author_facet | Xuanzhe Liu Yuange Li Shuo Wang Mingkuan Lu Jian Zou Zhongmin Shi Binbin Xu Wei Wang Bo Hu Tuo Jin Fei Wu Shen Liu Cunyi Fan |
| author_sort | Xuanzhe Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T19:45:54Z |
| format | Article |
| id | doaj.art-490affed61cb4a83ad7791ee9f1bad40 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-11T19:45:54Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-490affed61cb4a83ad7791ee9f1bad402022-12-22T04:06:29ZengElsevierMaterials Today Bio2590-00642022-12-0116100428PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesisXuanzhe Liu0Yuange Li1Shuo Wang2Mingkuan Lu3Jian Zou4Zhongmin Shi5Binbin Xu6Wei Wang7Bo Hu8Tuo Jin9Fei Wu10Shen Liu11Cunyi Fan12Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Spine Surgery, Changzheng Hospital, Naval Medical University, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China; Corresponding author.Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Corresponding author.Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Corresponding author. Cunyi Fan,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.http://www.sciencedirect.com/science/article/pii/S2590006422002265PDGFMicroneedleTendon healingp38/cyclin D1 pathwayAngiogenesis |
| spellingShingle | Xuanzhe Liu Yuange Li Shuo Wang Mingkuan Lu Jian Zou Zhongmin Shi Binbin Xu Wei Wang Bo Hu Tuo Jin Fei Wu Shen Liu Cunyi Fan PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis Materials Today Bio PDGF Microneedle Tendon healing p38/cyclin D1 pathway Angiogenesis |
| title | PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis |
| title_full | PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis |
| title_fullStr | PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis |
| title_full_unstemmed | PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis |
| title_short | PDGF-loaded microneedles promote tendon healing through p38/cyclin D1 pathway mediated angiogenesis |
| title_sort | pdgf loaded microneedles promote tendon healing through p38 cyclin d1 pathway mediated angiogenesis |
| topic | PDGF Microneedle Tendon healing p38/cyclin D1 pathway Angiogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006422002265 |
| work_keys_str_mv | AT xuanzheliu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT yuangeli pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT shuowang pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT mingkuanlu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT jianzou pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT zhongminshi pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT binbinxu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT weiwang pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT bohu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT tuojin pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT feiwu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT shenliu pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis AT cunyifan pdgfloadedmicroneedlespromotetendonhealingthroughp38cyclind1pathwaymediatedangiogenesis |