| Title | Integrated bioactive scaffold with aptamer-targeted stem cell recruitment and growth factor-induced pro-differentiation effects for anisotropic meniscal regeneration |
| Authors | Li, Hao Zhao, Tianyuan Cao, Fuyang Deng, Haoyuan He, Songlin Li, Jianwei Liu, Shuyun Yang, Zhen Yuan, Zhiguo Guo, Quanyi |
| Affiliation | Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Inst Orthoped, Beijing, Peoples R China Key Lab Musculoskeletal Trauma & War Injuries PLA, Beijing Key Lab Regenerat Med Orthoped, Beijing, Peoples R China Nankai Univ, Sch Med, Tianjin 300071, Peoples R China Zhengzhou Univ, Affiliated Hosp 1, Dept Orthoped, Zhengzhou, Peoples R China Peking Univ, Peking Univ Peoples Hosp, Arthrit Clin & Res Ctr, Beijing 100044, Peoples R China Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Bone & Joint Surg, Shanghai, Peoples R China |
| Keywords | REPAIR REGION |
| Issue Date | Mar-2022 |
| Publisher | BIOENGINEERING & TRANSLATIONAL MEDICINE |
| Abstract | Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue-engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor-beta 3 (TGF-beta 3)-loaded PLGA microparticles (MPs) were mixed with aptamer-conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium-derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF-beta 3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF-scaffolds increased neomeniscal formation in rabbit critical-sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ. |
| URI | http://hdl.handle.net/20.500.11897/638803 |
| DOI | 10.1002/btm2.10302 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
