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3D-Printed PCL Scaffolds Loaded with bFGF and BMSCs(PCLMF) Enhance Tendon-Bone Healing in Rat Rotator Cuff Tears by Immunomodulation and Osteogenesis Promotion

ABSTRACT: Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. 3D printing, a promising technology, enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multi-differentiation potential and valuable immunomodulatory effects. Basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed PCL scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks post-surgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.

ORGANISM(S): Mus musculus

PROVIDER: GSE277270 | GEO | 2024/09/30

REPOSITORIES: GEO

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Project description:Objective To identify transcript level differences between traumatic and degenerative tears of tendon tissues in shoulder joint using RNA-seq. Methods Tendon tissues were isolated from female and male patients with traumatic or degenerative tears during arthroscopic surgery (N = 31). Differentially expressed transcript were identified and biological processes enriched in traumatic and degenerative tears were probed computationally. Expression pattern of selected transcripts was validated by real-time qPCR. Results We identified 339 and 336 transcripts differentially expressed between traumatic and degenerative tears in females and males respectively at a fold-change greater than |2| and a p-value  0.05. In females, GSTM1, MT1G, S1008A, ACSM3, DSC, FAM110C and VNN2 were the most prominent transcripts elevated in traumatic tears and CHAD, CLEC3A, IBSP, TNMD, APLNR, and CPA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented catabolic processes, immune response, and metabolic processes while those repressed in traumatic tears represented tissue morphogenesis and developmental processes, angiogenesis, and extracellular matrix organization. In males, ELOA3B, CXCL8, ADM, TNS4 and SPOCK1 were the most prominent transcripts elevated in traumatic tears and MYL2, TNNC1, MB, CPA3, APLNR, and CA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented localization of endoplasmic reticulum, chromosome organization, leukocyte/neutrophil degranulation, and protein transport whereas those repressed in traumatic tears represented muscle development, blood circulation (angiogenesis), and muscle cell differentiation. Numerous novel lncRNAs were also identified to be differentially expressed between traumatic and degenerative tears in both sexes. Conclusions and Clinical Relevance This study improves our molecular understanding of tendon tissues in patients with rotator cuff tendinopathy based on underlying etiology (trauma and degeneration). It also provides new insights into sex-based transcript differences that may help drive clinical decision making in female and male patients with traumatic and degenerative shoulder injuries.

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3D-Printed PCL Scaffolds Loaded with bFGF and BMSCs(PCLMF) Enhance Tendon-Bone Healing in Rat Rotator Cuff Tears by Immunomodulation and Osteogenesis Promotion

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