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Science of Advanced Materials · 2024 ·Vol. 16 ·期 11 ·1157-1166 · IF 0.9

Application of Alginate-Collagen Hydrogel and Its Related Mechanisms in the Repair of Rat Cartilage Injuries

Li Yezhou,Tang Chengjian

This research investigated the application of alginate-collagen hydrogel (ACH) in rat cartilage injury (CI) repair and its related mechanisms through in vitro and in vivo experiments. Alginate solution and modified collagen solution were mixed to prepare the ACH. The obtained samples were characterized and their sustained release properties were determined. L929 mouse fibroblasts were assigned into a blank control group (BC group, untreated), a positive control group (PC group, treated with 6.4% phenol), a negative control group (NC group, treated with tissue culture polystyrene), and an ACH group (treated with ACH). Cell viability was assessed using the MTT assay. Meanwhile, the cytotoxicity of the ACH and its impact on cell proliferation and cell attachment capabilities were analyzed. Thirty 4-week-old specific pathogen-free (SPF) Sprague Dawley (SD) rats were randomly grouped into a chondrocyte group (5 rats, chondrocytes collected and cultured), a cPAGE group (5 rats, chondrocytes treated with ACH), a model group (10 rats, CI model), and a mPAGE group (10 rats, CI model treated with CAH). The influence of CAH on chondrocyte proliferation and the type II collagen (COLII) expression were assessed using the cell counting kit 8 (CCK-8) assay and immunofluorescence staining. Furthermore, the impacts of CAH on chondrocyte tissue and COL-II expression were analyzed using Safranin O-Fast Green (SOFG) staining, the International Cartilage Repair Society (ICRS) score, and COL-II tissue staining. Immunoblotting was utilized to detect the TNF-α, NF-κB, matrix metalloproteinase 13 (MMP-13), and COL-II proteins in cartilage tissue. The results showed that release rate (RR) of the constructed ACH reached over 85% within 72 hours and achieved degradation equilibrium within 5 days with a weight loss (WL) rate of over 60%. L929 fibroblasts culture results showed that the ACH posed no significant cytotoxicity, and cell attachment results were not obviously different from those on tissue culture plates (P >0.05). MTT assay results demonstrated that the ACH exerted no adverse effects on L929 cell proliferation and growth, indicating a good biocompatibility. CCK-8 and COL-II results indicated that chondrocyte proliferation in cPAGE group was much higher in contrast to that in chondrocyte group (P <0.05). Besides, the animal experiments unveiled that in comparison to the CI group, the mPAGE group had more chondrocytes, upregulated COL-II, and higher ICRS scores (P <0.05). MMP-13, NF-κB, and TNF-α were downregulated, and COL-II was upshifted in the mPAGE group, with remarkable differences (P <0.05). In conclusion, ACH exhibited excellent biocompatibility and low cytotoxicity, promoted cell proliferation and growth, facilitated chondrocyte proliferation in rat CI repair, offering a valuable research foundation for CI treatment.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 骨科
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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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Acta Biomaterialia · 2023 · IF 9.7

A hydrogel reservoir as a self-contained nucleus pulposus cell delivery vehicle for immunoregulation and repair of degenerated intervertebral disc

Yulin Jiang,Juehan Wang,Dan Sun,Zheng Liu,Lin Qi,Meixuan Du,Jing Wang,Yubao Li,Ce Zhu,Yong Huang,Yueming Song,Limin Liu,Ganjun Feng,Li Zhang

The strategies for modulating the local inflammatory microenvironment to inhibit intervertebral disc degeneration (IVDD) have garnered significant interest in recent years. In this study, we developed a "self-contained" injectable hydrogel capable of storing Mg 2+ while carrying nucleus pulposus (NP) cells, with the aim of inhibiting IVDD through immunoregulation . The hydrogel consists of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC), and NP cells. When injected into the NP site, PNIPAAm gelates instantly under body temperature, forming an interpenetrating network (IPN) hydrogel with SA. Ca 2+ released from the SC can crosslink the SA in situ , forming a SA/PNIPAAm hydrogel with an interpenetrating network (IPN) encapsulating the NP cells. Moreover, inside the hydrogel, Mg 2+ released from SC are effectively encapsulated and maintained at a desirable concentration. These Mg 2+ facilitates the local cell matrix synthesis and promotes immunomodulation (upregulating M2 / downregulating M1 macrophage polarization), thus inhibiting the IVDD progression. The proposed hydrogel has biocompatibility and is shown to enhance the expression of collagen II (COL II) and aggrecan . The potential of the injectable hydrogel in IVD repair has also been successfully demonstrated by in vivo studies. Statement of significance • A unique injectable hydrogel consisting of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC) and nucleus pulposus cells, has been created for intervertebral disc repair applications. • This is the first “self-contained” cell delivery system capable of releasing and subsequently storing Mg 2+ in the hydrogel reservoir for localized treatment. • The role of Mg 2+ in regulating the macrophage polarity transformation (from pro-inflammatory M1 to anti-inflammatory M2 phenotype) has been unveiled in the context of intervertebral disc repair.

研究领域: 生物材料 · 组织工程 · 再生医学 · 生物医学工程 · 骨科
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