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Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration

ABSTRACT: Osteochondral defects (OCD) cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation. Conventional strategies, such as the control of implant microstructure or the introduction of growth factors, have limited functions failing to manage these complex environments. Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes (CuTA@SF) to provide a suitable microenvironment for enhanced OCD regeneration. The incorporation of CuTA nanozymes endowed the SF hydrogel with a uniform microstructure and elevated hydrophilicity. In vitro cultivation of mesenchymal stem cells (MSCs) and chondrocytes showed that CuTA@SF hydrogel accelerated cell proliferation and enhanced cell viability, as well as had antioxidant and antibacterial properties. Under the inflammatory environment with the stimulation of IL-1β, CuTA@SF hydrogel still possessed the potential to promote MSC osteogenesis and deposition of cartilage-specific extracellular matrix (ECM). The proteomics analysis further confirmed that CuTA@SF hydrogel promoted cell proliferation and ECM synthesis. In the full-thickness OCD model of rabbit, CuTA@SF hydrogel displayed successfully in situ OCD regeneration, as evidenced by micro-CT, histology (HE, S/O, and toluidine blue staining) and immunohistochemistry (Col I and aggrecan immunostaining). Therefore, CuTA@SF hydrogel is a promising biomaterial targeted at the regeneration of OCD.

ORGANISM(S): Rattus Norvegicus Mus Musculus

SUBMITTER: Wei Zhang

PROVIDER: PXD031852 | iProX | Fri Mar 04 00:00:00 GMT 2022

REPOSITORIES: iProX

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Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration.

Cao Zhicheng Z Wang Hongmei H Chen Jialin J Zhang Yanan Y Mo Qingyun Q Zhang Po P Wang Mingyue M Liu Haoyang H Bao Xueyang X Sun Yuzhi Y Zhang Wei W Yao Qingqiang Q

Bioactive materials 20220531

Osteochondral defects (OCD) cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation. Conventional strategies, such as the control of implant microstructure or the introduction of growth factors, have limited functions failing to manage these complex environments. Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes (CuTA@SF) to provide a ...[more]

PMID: 35702612

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Project description:Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, yet this remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide for diabetic wound treatment. The dimeric copper peptide (D-CuP) was first synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biologic stability against proteases and the broad biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration. Meanwhile, the hydrogel matrix, exhibiting excellent ROS-scavenging capabilities, has been engineered to an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrated superior therapeutic efficacy, achieving in 97.2% closure of infected wounds.In this study, we present a proof-of-concept study to optimize the treatment of diabetic wounds. This method integrates a dimeric copper peptide hydrogel (G/D-CuP) to address several critical factors: i) The design and synthesis of the dimeric copper peptide (D-CuP) feature a broad range of targets and enhanced biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration; ii) Utilizing the steric hindrance conferred by dimerization reduces protease access to the active site and significantly improving stability against proteases; iii) A ROS-responsive hydrogel matrix has been synthesized, exhibiting superior ROS-scavenging capabilities, functioning as an intelligent drug reservoir that enables the controlled release of D-CuP at the wound interface while simultaneously attenuating inflammatory responses in the microenvironment; iv) G/D-CuP possesses outstanding deformability and spreadability, allowing it to adapt to any wound shape; v) The synthesis and preparation process of G/D-CuP are straightforward and cost-effective, making it highly promising for clinical translation. This multifunctional treatment platform is anticipated to accommodate the complex and dynamic biological processes involved in diabetic wound healing, thereby significantly improving the overall efficacy of wound healing treatments.

Project description:Purpouse: Aims of this study were (1) to characterize the endometrial transcriptome, (2) to identify functional pathways, and (3) to molecularly characterize selected pathways overrepresented in the endometrium of day 7 post-ovulation induction of cows treated to ovulate larger versus smaller follicles Methods: Seventy-four multiparous, nonlactating, presynchronized Nelore cows received a progesterone-releasing device and estradiol benzoate on Day–10 (D?10). Animals received cloprostenol (large follicle-large CL group; LF-LCL; N = 35) or not (small follicle-small CL group; SF-SCL; N = 39) on D?10. Progesterone devices were withdrawn and cloprostenol administered 42 to 54 hours (LF-LCL) or 30 to 36 hours (SF-SCL) before GnRH treatment (D0). Tissues were collected at slaughter on D7. Transcriptional profiling of the endometrial tissue was performed by RNA-seq and protein markers for proliferation and apoptosis were identified by immunohistochemistry. Results: Functional enrichment data indicated that LF-LCL endometrium expressed greater abundance of genes associated with biosynthetic and metabolic processes, whereas SF-SCL endometrium .gene expression profile was biased towards cell proliferation. Extracellular matrix-related genes were also upregulated in the SF-SCL endometrium suggesting reorganization of the ECM towards a proliferation permissive phenotype. Immunohistochemistry data confirmed the greater proliferative activity observed in SF-SCL endometrium I comparison to LF-LCL counterparts, and indicated a time-related transition within experimental group. In conclusion, the periovulatory endocrine milieu regulates bovine endometrial gene expression. Furthermore, timing and amplitude of ovarian steroid secretion pattern seem to determine the transition from a proliferation permissive to a biosynthetic and metabolically active endometrial phenotype, which may be associated with the preparation of an optimally receptive uterine environment. Conclusion: the periovulatory endocrine milieu affected D7 endometrial molecular signature. Main pathways affected were related to cell proliferation, ECM composition and remodeling, biosynthetic and metabolic processes. Reported data further suggest that the endometrial tissue from LF-LCL cows experienced an early proliferative phase (D4), whereas the SF-SCL endometrium, exposed to a distinct periovulatory endocrine environment, expressed a delayed onset of the proliferative activity (D7). endometrial mRNA profiles of endocrine manipulated cows were generated by deep sequencing using Illumina HiScanSQ platform

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Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration

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Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration.

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