Correction: Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants.

Correction for 'Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants' by Shiqing Ma et al., Biomater. Sci., 2022, 10, 4773-4784, https://doi.org/10.1039/D2BM00725H.

A drug delivery system constructed by a fusion peptide capturing exosomes targets to titanium implants accurately resulting the enhancement of osseointegration peri-implant.

BACKGROUND: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient's body and expected to find a method to treat implant with BMSC-exos in vivo directly. METHODS: A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface. RESULTS: Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy. CONCLUSION: This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.

Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants.

Titanium (Ti) and its alloys have been universally used as surgical implants, and the clinical need for modifying titanium surfaces to accelerate early stage osseointegration and prevent implant loosening is in huge demand. 3D printing technology is an accurate and controllable method to create titanium implants with complex nanostructures, which provide enough space to react and fit in the microenvironment of cells. Recently, extracellular vesicles (EVs) have attracted attention in promoting osteogenesis. The vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) have been proved to pack osteogenic-relative RNAs thereby regulating the osteogenic differentiation and mineralization of the target BMSCs. Arg-Gly-Asp (RGD)-derived peptides are typical peptides used to improve cell attachment and proliferation in bone tissue engineering. A novel strategy is proposed to load RGD-derived peptides on EVs with a fusion peptide (EVsRGD) and colonize EVsRGD on the titanium surface via a specific bonding peptide. In this study, we verify that the presence of EVsRGD enables the realization of the synergetic effect of EVs and RGD, enhancing the osteogenic differentiation and mineralization of BMSCs in vitro, resulting in satisfactory osseointegration around implants in vivo.

Functional extracellular matrix hydrogel modified with MSC-derived small extracellular vesicles for chronic wound healing.

OBJECTIVES: Diabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds. MATERIALS AND METHODS: Small extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa-based hydrogel material through peptides (SC-Ps-sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC-Ps-sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC-Ps-sEVs. The diabetic wound model was used to investigate the function/role of SC-Ps-sEVs hydrogel in promoting wound healing. RESULTS: A functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full-thickness skin wounds healing in diabetic rat model. CONCLUSIONS: This work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.

Chimeric Peptides Quickly Modify the Surface of Personalized 3D Printing Titanium Implants to Promote Osseointegration.

Titanium (Ti) and titanium alloys have been widely used in the field of biomedicine. However, the unmatched biomechanics and poor bioactivities of conventional Ti implants usually lead to insufficient osseointegration. To tackle these challenges, it is critical to develop a novel Ti implant that meets the bioadaptive requirements for load-bearing critical bone defects. Notably, three-dimensional (3D)-printed Ti implants mimic the microstructure and mechanical properties of natural bones. Additionally, eco-friendly techniques based on inorganic-binding peptides have been applied to modify Ti surfaces. Herein, in our study, Ti surfaces were modified to reinforce osseointegration using chimeric peptides constructed by connecting W9, RP1P, and minTBP-1 directly or via (GP)4, respectively. PR1P is derived from the extracellular VEGF-binding domain of prominin-1, which increases the expression of VEGF and promotes the binding of VEGF to endothelial cells, thereby accelerating angiogenesis. W9 induces osteoblast differentiation in bone marrow mesenchymal stem cells and human mesenchymal stem cells to promote bone formation. Overall, chimeric peptides promote osseointegration by promoting angiogenesis and osteogenesis. Additionally, chimeric peptides with P3&4 were more effective than those with P1&2 in improving osseointegration, which might be ascribed to the capacity of P3&4 to provide a greater range for chimeric peptides to express their activity. This work successfully used chimeric peptides to modify 3D-Ti implant surfaces to improve osseointegration on the implant-bone surface.

Evaluation of self-prepared absorbable hemostatic cellulose fibrils.

To evaluate the effectiveness and safety of self-prepared absorbable hemostatic fibrils.A kind of absorbable hemostatic fibrils were prepared by self-developed patent technique. The physical form and molecular structure of the fibrils and a marketed product Surgicel were characterized by general observation and infrared spectroscopy; the carboxyl content, pH value and relative molecular mass of fibrils were determined by potentiometric titration method, pH meter and copper ethylenediamine method, respectively. The behavior of the fibrils and Surgicel in contact with blood was observed by inverted microscope, the cytotoxicity was evaluated by agarose diffusion cell assay . The external iliac artery hemorrhage model and the back muscle infiltration model in rats were established. The hemostatic effectiveness of the fibrils was investigated by hemostasis time and blood weight, and the degradation and biosafety of fibrils were investigated by observation photography, immune organ weighing, hematology and coagulation index measuring, and histopathological examination. The fibrils and Surgicel had similar molecular structures. Compared with the raw material regenerated cellulose, the typical carboxyl stretching vibration absorption peak of -COOH appeared near in both fibrils and Surgicel. The carboxyl content of the two materials was about 20%, and the pH value was about 3. The relative molecular mass of the fibers after oxidation was 4466±79, which was close to that of Surgicel(>0.05). After contacting with blood, the volume of fibrils and Surgicel expanded, and absorbed blood of dozens of times as their own weight. The results of agar diffusion test showed that the fibrils had no cytotoxicity. The results of animal experiments showed that the hemostasis completed within and there was no significant difference in blood weight and speed of hemostasis between two products (both >0.05). The fibrils could be degraded 1 week after being implanted to the bleeding sites of the muscle. There were no pathological effects on the appearance, body weight, food intake, immunological tissue thymus, spleen, lymph nodes, hematology and coagulation indexes of the rats, and no obvious abnormality found in the histopathological examination. The prepared absorbable hemostatic fibrils have excellent biological safety and effectiveness.