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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Photo-driven dynamic hydrogel modulates bone marrow mesenchymal stem cells behavior for enhanced cartilage regeneration

Wenjie Zhang,Wenliang Xue,Zhaoli Jia,Rong Yang,Penghui Wang,Yi Hu,Xiaoyan Tan,Qiang Chen,Bo Chi

Regenerating damaged cartilage remains a challenge due to limited cell availability and inefficient chondrogenic differentiation. Here, we present a photo-driven dynamic hydrogel with a double-network structure to meet this challenge. The fabrication strategy involves a combination of a photosensitive host–guest network with a covalent network, providing tunable mechanical cues that effectively regulate bone marrow mesenchymal stem cells (BMSCs) behavior within their microenvironment while maintaining macroscopical stability. Employing a two-step stiffness-tunable process mediated by controlled low-dose light exposure, the hydrogel exerts precise control over BMSCs proliferation and orchestrates chondrogenic differentiation, leading to the upregulation of crucial chondrogenic genes, notably SOX9 and ACAN. Empirical evidence derived from histological analysis substantiates the functional efficacy of the hydrogel, confirming the regenerative potential of cartilage tissues. This study presents an innovative and promising strategy for stem cell culture, in vitro differentiation, and cell delivery, with implications for cartilage defect repair and tissue regeneration.

研究领域: 组织工程 · 干细胞生物学 · 生物医学材料 · 再生医学
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Science Advances · 2024 ·Vol. 10 ·期 42 · IF 11.7

Bioenergetic-active exosomes for cartilage regeneration and homeostasis maintenance

Xulong Liu,Shangtong Jiang,Ting Jiang,Ziyang Lan,Xin Zhang,Zhenyu Zhong,Xiaodan Wu,Cunjing Xu,Yingying Du,Shengmin Zhang

Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO–encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.

研究领域: 再生医学 · 细胞代谢 · 组织工程 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Increased physiological osteochondral repair via space-specific sequestrating endogenous BMP-2 founctional hydrogel

Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo

The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.

CAS / MDL: 106797-53-9 760-93-0
研究领域: 组织工程 · 再生医学 · 生物材料科学 · 骨科
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