3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats
Introduction: Regeneration of critical-sized bone defects remains a major clinical challenge. Solely promoting osteogenesis is inadequate, because vasculature and neural innervation are critical for establishing the bone regenerative microenvironment. Objective: For the first time, the present study...
I tiakina i:
| Ngā kaituhi matua: | , , , , , , , , , , |
|---|---|
| Hōputu: | Tuhinga |
| Reo: | Ingarihi |
| I whakaputaina: |
KeAi Communications Co., Ltd.
2025-09-01
|
| Rangatū: | Bioactive Materials |
| Ngā marau: | |
| Urunga tuihono: | http://www.sciencedirect.com/science/article/pii/S2452199X25001975 |
| Tags: |
Tāpirihia he Tūtohu
No Tags, Be the first to tag this record!
|
| _version_ | 1839582672467263488 |
|---|---|
| author | Minjia Zhu Xinyi Li Le Xiao Kan Yu Jingyi Li Zixiang Dai Qinrou Zhang Jialiang Dai Zihan Jia Yuxing Bai Ke Zhang |
| author_facet | Minjia Zhu Xinyi Li Le Xiao Kan Yu Jingyi Li Zixiang Dai Qinrou Zhang Jialiang Dai Zihan Jia Yuxing Bai Ke Zhang |
| author_sort | Minjia Zhu |
| collection | DOAJ |
| description | Introduction: Regeneration of critical-sized bone defects remains a major clinical challenge. Solely promoting osteogenesis is inadequate, because vasculature and neural innervation are critical for establishing the bone regenerative microenvironment. Objective: For the first time, the present study developed 3D bio-printed hydrogel microfibers (aMF) encapsulating human periodontal ligament stem cells (hPDLSCs) in a tri-culture system in calcium phosphate cement (CPC) scaffold with a two-stage metformin release for regeneration of nerve, vasculature, and bone. Materials and methods: This tri-culture system consisted of hPDLSCs, human umbilical vein endothelial cells (hUVECs), and pericytes (PCs). Moreover, we employed 3D-bioprinted aMF in CPC scaffold with a controlled two-stage release system for metformin release to promote bone, vasculature, and nerve regeneration. Results: Our innovative construct increased the regenerated amounts of bone, vasculature and nerve significantly by 2.5-fold, 3-fold, and 3.5-fold, respectively, than control group, in cranial defects in rats. Conclusion: This novel hPDLSCs tri-culture system in aMF-CPC scaffold with two-stage metformin release is highly promising for the regeneration of all three tissues of bone, vasculature, and nerves in a wide range of craniofacial and orthopedic applications. |
| format | Article |
| id | doaj-art-eafefd57fb62443db1663db539ed1021 |
| institution | Matheson Library |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-eafefd57fb62443db1663db539ed10212025-08-04T04:24:39ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-09-01513994133D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in ratsMinjia Zhu0Xinyi Li1Le Xiao2Kan Yu3Jingyi Li4Zixiang Dai5Qinrou Zhang6Jialiang Dai7Zihan Jia8Yuxing Bai9Ke Zhang10Department of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Dentistry, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR ChinaDepartment of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR China; Corresponding author.Department of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100070, PR China; Corresponding author.Introduction: Regeneration of critical-sized bone defects remains a major clinical challenge. Solely promoting osteogenesis is inadequate, because vasculature and neural innervation are critical for establishing the bone regenerative microenvironment. Objective: For the first time, the present study developed 3D bio-printed hydrogel microfibers (aMF) encapsulating human periodontal ligament stem cells (hPDLSCs) in a tri-culture system in calcium phosphate cement (CPC) scaffold with a two-stage metformin release for regeneration of nerve, vasculature, and bone. Materials and methods: This tri-culture system consisted of hPDLSCs, human umbilical vein endothelial cells (hUVECs), and pericytes (PCs). Moreover, we employed 3D-bioprinted aMF in CPC scaffold with a controlled two-stage release system for metformin release to promote bone, vasculature, and nerve regeneration. Results: Our innovative construct increased the regenerated amounts of bone, vasculature and nerve significantly by 2.5-fold, 3-fold, and 3.5-fold, respectively, than control group, in cranial defects in rats. Conclusion: This novel hPDLSCs tri-culture system in aMF-CPC scaffold with two-stage metformin release is highly promising for the regeneration of all three tissues of bone, vasculature, and nerves in a wide range of craniofacial and orthopedic applications.http://www.sciencedirect.com/science/article/pii/S2452199X25001975Bone tissue engineeringInnervationOsteogenesisTri-cultureMetformin |
| spellingShingle | Minjia Zhu Xinyi Li Le Xiao Kan Yu Jingyi Li Zixiang Dai Qinrou Zhang Jialiang Dai Zihan Jia Yuxing Bai Ke Zhang 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats Bioactive Materials Bone tissue engineering Innervation Osteogenesis Tri-culture Metformin |
| title | 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats |
| title_full | 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats |
| title_fullStr | 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats |
| title_full_unstemmed | 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats |
| title_short | 3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats |
| title_sort | 3d printed microfibers encapsulating stem cells in scaffold with tri culture and two stage metformin release for bone vasculature nerve regeneration in rats |
| topic | Bone tissue engineering Innervation Osteogenesis Tri-culture Metformin |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25001975 |
| work_keys_str_mv | AT minjiazhu 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT xinyili 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT lexiao 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT kanyu 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT jingyili 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT zixiangdai 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT qinrouzhang 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT jialiangdai 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT zihanjia 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT yuxingbai 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats AT kezhang 3dprintedmicrofibersencapsulatingstemcellsinscaffoldwithtricultureandtwostagemetforminreleaseforbonevasculaturenerveregenerationinrats |