ZIF-8 induced hydroxyapatite-like crystals enabled superior osteogenic ability of MEW printing PCL scaffolds.

ZIF-8 may experience ion-responsive degradation in ionic solutions, which will change its initial architecture and restrict its direct biological use. Herein, we report an abnormal phenomenon in which ZIF-8 induces large hydroxyapatite-like crystals when soaked directly in simulated body fluid. These crystals grew rapidly continuously for two weeks, with the volume increasing by over 10 folds. According to Zn2+ release and novel XRD diffraction peak presence, ZIF-8 particles can probably show gradual collapse and became congregate through re-nucleation and competitive coordination. The phenomenon could be found on ZIF-8/PCL composite surface and printed ZIF-8/PCL scaffold surface. ZIF-8 enhanced PCL roughness through changing the surface topography, while obviously improving the in-vivo and in-vitro osteoinductivity and biocompatibility. The pro-biomineralization property can make ZIF-8 also applicable in polylactic acid-based biomaterials. In summary, this study demonstrates that ZIF-8 may play the role of a bioactive additive enabling the surface modification of synthetic polymers, indicating that it can be applied in in-situ bone regeneration.

Clay Sculpture-Inspired 3D Printed Microcage Module Using Bioadhesion Assembly for Specific-Shaped Tissue Vascularization and Regeneration.

3D bioprinting techniques have enabled the fabrication of irregular large-sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)-gelatin-dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.

Reconfigurable Magnetic Liquid Building Blocks for Constructing Artificial Spinal Column Tissues.

All-liquid molding can be used to transform a liquid into free-form solid constructs, while maintaining internal fluidity. Traditional biological scaffolds, such as cured pre-gels, are normally processed in solid state, sacrificing flowability and permeability. However, it is essential to maintain the fluidity of the scaffold to truly mimic the complexity and heterogeneity of natural human tissues. Here, this work molds an aqueous biomaterial ink into liquid building blocks with rigid shapes while preserving internal fluidity. The molded ink blocks for bone-like vertebrae and cartilaginous-intervertebral-disc shapes, are magnetically manipulated to assemble into hierarchical structures as a scaffold for subsequent spinal column tissue growth. It is also possible to join separate ink blocks by interfacial coalescence, different from bridging solid blocks by interfacial fixation. Generally, aqueous biomaterial inks are molded into shapes with high fidelity by the interfacial jamming of alginate surfactants. The molded liquid blocks can be reconfigured using induced magnetic dipoles, that dictated the magnetic assembly behavior of liquid blocks. The implanted spinal column tissue exhibits a biocompatibility based on in vitro seeding and in vivo cultivating results, showing potential physiological function such as bending of the spinal column.

Graphene Oxide Functionalized Double-Layered Patch with Anti-Adhesion Ability for Abdominal Wall Defects.

BACKGROUND: Effective repair of full-thickness abdominal wall defects requires a patch with sufficient mechanical strength and anti-adhesion characteristics to avoid the formation of hernias and intra-abdominal complications such as intestinal obstruction and fistula. However, patches made from polymers or bio-derived materials may not meet these requirements and lack the bionic characteristics of the abdominal wall. MATERIALS AND METHODS: In this study, we report a consecutive electrospun method for preparing a double-layer structured nanofiber membrane (GO-PCL/CS-PCL) using polycaprolactone (PCL), graphene oxide (GO) and chitosan (CS). To expand the bio-functions (angiogenesis/reducing reactive oxygen species) of the patch (GO-PCL/NAC-CS-PCL), N-acetylcysteine (NAC) was loaded for the repair of full-thickness abdominal wall defects (2×1.5cm) in rat model. RESULTS: The double-layered patch (GO-PCL/NAC-CS-PCL) showed excellent mechanical strength and biocompatibility. After 2 months, rats treated with the patch exhibited the desired repair effect with no hernia formation, less adhesion (adhesion score: 1.50±0.50, P<0.001) and more collagen deposition (percentage of collagen deposition: 34.94%±3.31%, P<0.001). CONCLUSION: The double-layered nanomembranes presented in this study have good anti-hernia and anti-adhesion effects, as well as improve the microenvironment in vivo. It, therefore, holds good prospects for the repair of abdominal wall defects and provides a promising key as a postoperative anti-adhesion agent.

A biocompatible vascularized graphene oxide (GO)-collagen chamber with osteoinductive and anti-fibrosis effects promotes bone regeneration in vivo.

The survival of transplanted cells and tissues in bone regeneration requires a microenvironment with a vibrant vascular network. A tissue engineering chamber can provide this in vivo. However, the commonly used silicone chamber is biologically inert and can cause rejection reactions and fibrous capsule. Studies have revealed that collagen is highly biocompatible and graphene oxide (GO) could regulate osteogenic activity in vivo. Besides, GO can be cross-linked with natural biodegradable polymers to construct scaffolds. Methods: A vascularized GO-collagen chamber model was built by placing vessels traversing through the embedded tissue-engineered grafts (osteogenic-induced bone mesenchymal stem cells -gelatin) in the rat groin area. Osteogenic activity and inflammatory reactions were assessed using different methods including micro-CT scanning, Alizarin red staining, and immunohistochemical staining. Results: After one month, in vivo results showed that bone mineralization and inflammatory responses were significantly pronounced in the silicone model or no chamber (control) groups. Vascular perfusion analysis confirmed that the GO-collagen chamber improved the angiogenic processes. Cells labeled with EdU revealed that the GO-collagen chamber promoted the survival and osteogenic differentiation of bone mesenchymal stem cells. Conclusion: Overall, the novel biocompatible GO-collagen chamber exhibited osteoinductive and anti-fibrosis effects which improved bone regeneration in vivo. It can, therefore, be applied to other fields of regenerative medicine.

Multi-Layered Polyamide/Collagen Scaffolds with Topical Sustained Release of N-Acetylcysteine for Promoting Wound Healing.

BACKGROUND: Impaired wound healing might be associated with many issues, especially overactive of reactive oxygen species (ROS), deficiency of blood vessels and immature of epidermis. N-acetylcysteine (NAC), as an antioxidant, could solve these problems by inhibiting overreactive of ROS, promoting revascularization and accelerating re-epithelialization. How to deliver NAC in situ with a controllable releasing speed still remain a challenge. MATERIALS AND METHODS: In this study, we combined collagen (Col) with N-acetylcysteine to perform the characteristics of sustained release and chemically crosslinked Col/NAC composite with polyamide (PA) nanofibers to enhance the mechanical property of collagen and fabricated this multi-layered scaffold (PA-Col/NAC scaffold). The physical properties of the scaffolds such as surface characteristics, water absorption and tensile modulus were tested. Meanwhile, the ability to promote wound healing in vitro and in vivo were investigated. RESULTS: These scaffolds were porous and performed great water absorption. The PA-Col/NAC scaffold could sustainably release NAC for at least 14 days. After cell implantation, PA-Col/NAC scaffold showed better cell proliferation and cell migration than the other groups. In vivo, PA-Col/NAC scaffolds could promote wound healing best among all the groups. CONCLUSION: The multi-layered scaffolds could obviously accelerate the process of wound healing and exert better and prolonged effects.

Biocompatible graphene oxide-collagen composite aerogel for enhanced stiffness and in situ bone regeneration.

The developing bone graft substitutes have become a promising strategy for repairing large bone loss. Aerogels that made from natural polymers were widely investigated for synthetic bone graft due to their high porosity and great biocompatibility. However, the mechanical properties of natural polymer aerogel are extremely poor for large bone repair. Graphene oxide (GO) is one of the nanomaterials with great mechanical properties as well as biocompatibility, making it a promising component when constructing hybrid aerogels for bone regeneration. In the present study, we have developed a highly porous aerogel consist of GO and type I collagen (COL) using sol-gel process (concentrations of GO: 0%, 0.05%, 0.1%, and 0.2% w/v). Results indicated that GO-COL aerogels were highly porous and hydrophilic. Furthermore, the compressive modulus of GO-COL aerogels was enhanced with the GO concentration increased. For in vitro experiment, 0.1% GO-COL aerogel exhibited better biomineralization rate and cell compatibility than other groups of aerogels. For in vivo study, a better bone repair effect was observed in 0.1% GO-COL aerogels than COL aerogel in rat cranial defect models. This study indicated that 0.1% GO-COL aerogel exhibited good biocompatibility and osteogenic ability in vivo, which make it a promising biocompatible scaffold for bone regeneration and tissue engineering.

Sustained release of N-acetylcysteine by sandwich structured polycaprolactone/collagen scaffolds for wound healing.

PCL (poly-caprolactone) nanofibers have good biocompatibility and high porosity, which are usually utilized for application in wound dressings. However, wound healing could be hindered by the overproduction of reactive oxygen species (ROS) and different factors. Pure nanofibers cannot satisfy these requirements of wound healing. N-acetylcysteine (NAC), as an antioxidant, meets the requirements for wound healing by resisting the overproduction of ROS and by promoting angiogenesis and maturation of the epidermis. In this study, we prepared a sandwich structured PCL-Col/NAC scaffold using the molding method, which consisted of PCL nanofibers at the core and NAC-loaded collagen on both sides. The hydroscopicity and tensile modulus of PCL-Col/NAC scaffolds showed best performance of these properties among groups. Meanwhile, the drug release profiles of PCL-Col/NAC scaffolds were investigated using the HPLC method and the results suggested a sustained drug release of NAC for PCL-Col/NAC scaffolds. In addition, PCL-Col/NAC scaffolds presented better properties than the control groups in cell migration and proliferation. The in vivo wound healing therapy effect was studied using an oval (2 × 1 cm) full-thickness skin defect wound model for SD rats. After 21 days, gross view and histological analysis showed a favorable beneficial therapeutic effect as well as better epidermal maturation compared with the control groups. CD31 immunohistology results revealed relatively more new vessels in the PCL-Col/NAC group than the control groups. This study developed novel PCL-Col/NAC scaffolds with an excellent hydroscopicity, tensile modulus and the ability to promote epidermal maturation and angiogenesis, demonstrating its promising potential in wound healing treatment. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.