An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration

Zhang, Wei; Chen, Ling; Zhang, Aini; Liu, Haoyang; Jiang, Yujie; Li, Xiaolong; Sheng, Renwang; Yao, Qingqiang; Chen, Jialin

doi:10.1016/j.bioactmat.2020.05.003

Cited by 54 publications

(70 citation statements)

References 48 publications

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“…Since fibrosis exists in the entire pathological process, the release of BMP9 needs to last relative longer compared with VEGF. The release profiles of two bioactive factors could be adjusted by selecting two biomaterials with different degradation rates [ 41 ], or by pre-loading one of the factors in a secondary carrier [ [42] , [43] , [44] ]. For example, we added SF microspheres encapsulated with bone morphogenetic protein-2 (BMP2) into a SF scaffold, which was further functionalized with SDF-1 via physical adsorption.…”

Section: Resultsmentioning

confidence: 99%

Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

Chang

Chen

et al. 2021

Bioactive Materials

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Myocardial infarction (MI) is one of cardiovascular diseases that pose a serious threat to human health. The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery, necrosis of myocardial cells, inflammation, and myocardial fibrosis. Aiming at the treatment of different stages of MI, in this work, an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor (VEGF) and silk fibroin (SF) microspheres containing bone morphogenetic protein 9 (BMP9) for releasing VEGF and BMP9 to realize their respective functions. The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days, facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage, respectively. Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size. Taken together, these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function, showing a promising potential for cardiac clinical application.

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Section: Resultsmentioning

confidence: 99%

Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

Chang

Chen

et al. 2021

Bioactive Materials

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“…If nanoparticles can be accumulated more at the severely defective sites, the therapeutic outcome could be better than that evenly distributed in the articular cavity. The combination of hydrogels or scaffolds with nanoparticles can enhance the stability of nanoparticles and extend the retention of drugs following intra-articular injection [131][132][133] (Table 4). In addition, scaffolds or hydrogels can affect cell survival and provide matrix for cell homing and regeneration [131][132][133][134][135][136].…”

Section: Intra-articular Delivery Choicesmentioning

confidence: 99%

“…Kartogenin (KGN) as a small bioactive molecule to promote chondrogenic differentiation of stem cells was first reported by Johnson et al in 2012 [185]. KGN-loaded nanoparticles have been shown to play a critical role in chondrogenesis and promote cartilage repair in vivo [131,132,186].…”

Section: Promoting Chondrogenesismentioning

confidence: 99%

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Dai

Guo

et al. 2021

Nano-Micro Lett.

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Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of “smart” bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.

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“…Silk fibroin (SF) is a natural fibrous polymer that has been applied for osteochondral engineering due to its biocompatibility, biodegradability, high tensile strength, and excellent biological characteristics [ [18] , [19] , [20] ]. Nonetheless, traditional silk scaffolds focus mainly on the porous structure of the cartilage layer, which is incompatible with the native cartilage structure and disadvantageous for cartilage formation [ [21] , [22] , [23] , [24] ]. In addition, bilayer or trilayer silk scaffolds are often combined with β-tricalcium phosphate (β-TCP) or ceramics as a subchondral bone layer to obtain high mechanical strength, which results in poor interface strength between the cartilage layer (silk) and the subchondral bone layer (β-TCP or ceramics) [ 18 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels

Zhou

Jiang

et al. 2021

Bioactive Materials

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Osteochondral repair remains a major challenge in current clinical practice despite significant advances in tissue engineering. In particular, the lateral integration of neocartilage into surrounding native cartilage is a difficult and inadequately addressed problem that determines the success of tissue repair. Here, a novel design of an integral bilayer scaffold combined with a photocurable silk sealant for osteochondral repair is reported. First, we fabricated a bilayer silk scaffold with a cartilage layer resembling native cartilage in surface morphology and mechanical strength and a BMP-2-loaded porous subchondral bone layer that facilitated the osteogenic differentiation of BMSCs. Second, a TGF-β3-loaded methacrylated silk fibroin sealant (Sil-MA) exhibiting biocompatibility and good adhesive properties was developed and confirmed to promote chondrocyte migration and differentiation. Importantly, this TGF-β3-loaded Sil-MA hydrogel provided a bridge between the cartilage layer of the scaffold and the surrounding cartilage and then guided new cartilage to grow towards and replace the degraded cartilage layer from the surrounding native cartilage in the early stage of knee repair. Thus, osteochondral regeneration and superior lateral integration were achieved in vivo by using this composite. These results demonstrate that the new approach of marginal sealing around the cartilage layer of bilayer scaffolds with Sil-MA hydrogel has tremendous potential for clinical use in osteochondral regeneration.

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An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration

Cited by 54 publications

References 48 publications

Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels

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