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Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

ABSTRACT: MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3? to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.

SUBMITTER: Zhang X

PROVIDER: S-EPMC4735608 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

Zhang Xiaojin X Li Yan Y Chen Y Eugene YE Chen Jihua J Ma Peter X PX

Nature communications 20160114

MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds tha ...[more]

PMID: 26765931

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Project description:BackgroundTreating critically sized defects (CSDs) of bone remains a significant challenge in foot and ankle surgery. Custom 3D-printed implants are being offered to a small but growing subset of patients as a salvage procedure in lieu of traditional alternates such as structural allografts after the patient has failed prior procedures. The long-term outcomes of 3D-printed implants are still unknown and understudied because of the limited number of cases and short follow-up durations. The purpose of this study was to evaluate the outcomes of patients who received custom 3D-printed implants to treat CSDs of the foot and ankle in an attempt to aid surgeons in selecting appropriate surgical candidates.MethodsThis was a retrospective study to assess surgical outcomes of patients who underwent implantation of a custom 3D-printed implant made with medical-grade titanium alloy powder (Ti-6Al-4V) to treat CSDs of the foot and ankle between June 1, 2014, and September 30, 2019. All patients had failed previous nonoperative or operative management before proceeding with treatment with a custom 3D-printed implant. Univariate and multivariate odds ratios (ORs) of a secondary surgery and implant removal were calculated for perioperative variables.ResultsThere were 39 cases of patients who received a custom 3D-printed implant with at least 1 year of follow-up. The mean follow-up time was 27.0 (12-74) months. Thirteen of 39 cases (33.3%) required a secondary surgery and 10 of 39 (25.6%) required removal of the implant because of septic nonunion (6/10) or aseptic nonunion (4/10). The mean time to secondary surgery was 10 months (1-22). Multivariate logistic regression revealed that patients with neuropathy were more likely to require a secondary surgery with an OR of 5.76 (P = .03).ConclusionThis study demonstrated that 74% of patients who received a custom 3D-printed implant for CSDs did not require as subsequent surgery (minimum of 1-year follow-up). Neuropathy was significantly associated with the need for a secondary surgery. This is the largest series to date demonstrating the efficacy of 3D-printed custom titanium implants. As the number of cases using patient-specific 3D-printed titanium implant increases, larger cohorts of patients should be studied to identify other high-risk groups and possible interventions to improve surgical outcomes.Level of evidenceLevel IV, case series.

Project description:ObjectivesTo investigate the feasibility of the 3D printed scaffold for periapical bone defects.MethodsIn this study, antimicrobial peptide KSL-W-loaded PLGA sustainable-release microspheres (KSL-W@PLGA) were firstly prepared followed by assessing the drug release behavior and bacteriostatic ability against Enterococcus faecalis and Porphyromonas gingivalis. After that, we demonstrated that KSL-W@PLGA/collagen (COL)/silk fibroin (SF)/nano-hydroxyapatite (nHA) (COL/SF/nHA) scaffold via 3D-printing technique exhibited significantly good biocompatibility and osteoconductive property. The scaffold was characterized as to pore size, porosity, water absorption expansion rate and mechanical properties. Moreover, MC3T3-E1 cells were seeded into sterile scaffold materials and investigated by CCK-8, SEM and HE staining. In the animal experiment section, we constructed bone defect models of the mandible and evaluated its effect on bone formation. The Japanese white rabbits were killed at 1 and 2 months after surgery, the cone beam computerized tomography (CBCT) and micro-CT scanning, as well as HE and Masson staining analysis were performed on the samples of the operation area, respectively. Data analysis was done using ANOVA and LSD tests. (α = 0.05).ResultsWe observed that the KSL-W@PLGA sustainable-release microspheres prepared in the experiment were uniform in morphology and could gradually release the antimicrobial peptide (KSL-W), which had a long-term antibacterial effect for at least up to 10 days. HE staining and SEM showed that the scaffold had good biocompatibility, which was conducive to the adhesion and proliferation of MC3T3-E1 cells. The porosity and water absorption of the scaffold were (81.96 ± 1.83)% and (458.29 ± 29.79)%, respectively. Histological and radiographic studies showed that the bone healing efficacy of the scaffold was satisfactory.ConclusionsThe KSL-W@PLGA/COL/SF/nHA scaffold possessed good biocompatibility and bone repairing ability, and had potential applications in repairing infected bone defects. Clinical significance The 3D printed scaffold not only has an antibacterial effect, but can also promote bone tissue formation, which provides an alternative therapy option in apical periodontitis.

Dataset Information

Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

Publications

Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

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