Self-Reinforced PTLG Copolymer with Shish Kebab Structures and a Bionic Surface as Bioimplant Materials for Tissue Engineering Applications.

Green and biodegradable materials with great mechanical properties and biocompatibility will offer new opportunities for next-generation high-performance biological materials. Herein, the novel oriented shish kebab crystals of a novel poly(trimethylene carbonate-lactide-glycolide) (PTLG) vascular stent are first reported to be successfully fabricated through a feasible solid-state drawing process to simultaneously enhance the mechanical performance and biocompatibility. The crystal structure of this self-reinforced vascular stent was transformed from spherulites to a shish kebab crystal, which indicates the mechanical interlocking effect and prevents the lamellae from slipping with a significant improvement of mechanical strength to 333 MPa. Meanwhile, it is different from typical biomedical polymers with smooth surface structures, and the as-obtained PTLG vascular stent exhibits a bionic surface morphology with a parallel micro groove and ridge structure. These ridges and grooves were attributed to the reorganization of cytoskeleton fiber bundles following the direction of blood flow shear stress. The structure and parameters of these morphologies were highly similar to the inner surface of blood vessels of the human, which facilitates cell adhesion growth to improve its proliferation, differentiation, and activity on the surface of PTLG.

Fabrication and evaluation of 3D printed poly(l-lactide) copolymer scaffolds for bone tissue engineering.

The application of poly(L-lactic acid) (PLLA) in tissue engineering is limited due to its brittleness and uncontrollable degradation rate. In this study, the flexible p-dioxanone (PDO) and highly reactive glycolide (GA) units were introduced into PLLA segments by chemical modification to prepare poly(l-lactide-ran-p-dioxanone-ran-glycolide) (PLPG) copolymers. The copolymers were then processed into the PLPG scaffold by a 3D printing technology. The physicochemical properties of the PLPG copolymers were studied by NMR, DSC, XRD, GPC, and SEM. Furthermore, the mechanical properties, degradation properties, and biocompatibility of the PLPG scaffolds were also studied. The results showed that introducing PDO and GA units disrupted the regularity of PLLA, decreasing the crystallinity of the PLPG copolymers. However, introducing PDO and GA units could effectively improve the mechanical and degradation properties of the PLLA scaffolds. In vitro cell culture experiments indicated that the PLPG scaffolds supported proliferation, growth, and differentiation of MC3T3-E1 cells. The PLPG scaffolds reported herein, with controllable degradation rates and mechanical performance, may find applications in bone tissue engineering.

Biodegradable membrane of poly(l-lactide acid-dioxanone-glycolide) and stereocomplex poly(lactide) with enhanced crystallization and biocompatibility.

The membranes of poly(l-lactide acid-p-dioxanone-glycolide) (PLPG) with stereocomplex poly(lactic acid) (sc-PLA) were prepared by the solution blending way. It was observed that sc-PLA significantly heightened the crystallizing behavior of PLLA segments of the PLPG matrix. The crystallizing behavior displayed that the temperature of crystallization shifted to a higher range than that of PLPG. Moreover, the half-time of crystallization sharply decreased in value as the sc-PLA content increased in value on account of the pre-eminent nucleation ability of sc-PLA. TGA results revealed the thermal stability of the samples with the increase of sc-PLA compared to PLPG. Meanwhile, enzymatic degradation results indicated that the mass loss rate of the membrane decreased with the introduction of sc-PLA, but the overall degradation ability was still greater than that of PLLA. In the meantime, the biological experiment indicated that the membrane possessed low cytotoxicity.

Effects on the crystallization behavior and biocompatibility of poly(LLA-ran-PDO-ran-GA) with poly(d-lactide) as nucleating agents.

The blends of poly(l-lactide acid-p-dioxanone-glycolide) (PLPG) with poly(d-lactide) (PDLA) (PLPG/PDLA) were prepared by a solution-casting method. The effects of PDLA on the properties of the PLPG were studied. DSC and WAXD results confirmed that PLA stereocomplex (sc-PLA) crystals were formed by blending PLLA segments in PLPG with PDLA, and the melting endotherm for both PLLA and sc-PLA relied on PDLA content. The non-isothermal crystallization results indicated that the crystallization process was remarkably accelerated by the addition of PDLA. Meanwhile, the results of isothermal crystallization indicated that the half-time of crystallization decreased with the increase of PDLA content. Besides, the enzymatic degradation behavior of the samples showed that with the increase of PDLA content, the mass loss gradually decreased. Furthermore, TGA and DTG results indicated that the thermal degradation of the samples was a complex process. Moreover, the biocompatibility of the samples was tested by cell culture and using CCK-8 and live/dead staining. Results showed that the samples possessed lower cytotoxicity. Therefore, the PLPG/PDLA blends are promising candidate materials in biomedical applications.

Improving Mechanical Properties and Biocompatibilities by Highly Oriented Long Chain Branching Poly(lactic acid) with Bionic Surface Structures.

Exploiting the solid-state drawing (SSD) process toward polymer materials for medical implant devices is of significance to simultaneously improve the mechanical property and biocompatibility. Herein, for the first time, the bionic implants with a microvalley surface of oriented long chain branching PLA (b-PLA) was fabricated by a feasible SSD process. The as-obtained b-PLAs could not only show a high tensile strength (278.1 MPa) and modulus (4.32 GPa) but also bear a superior protein adsorption as high as 622 ng/cm2. Such exceptional mechanical properties and biocompatibility could be ascribed to the SSD process-induced highly orientation degree and the morphology of parallel grooves within ridges structures, resulting in the greatly enhanced crystallinity and surface hydrophobicity as well as a biocompatible vascular endothelial microstructure for cell to adhesion and growth and thus an improved proliferation, differentiation, and activity of osteoblasts with spindle-shaped and spread morphology on surface of the b-PLAs. These findings may pave the way for designing the novel biomaterials for vascular stent or tissue engineering devices by the SSD process.

Magnetic bioinspired micro/nanostructured composite scaffold for bone regeneration.

Magnetic-responsive materials are promising for applications in various biomedical fields. Especially, superparamagnetic nanoparticles are widely used in magnetic system for bone tissue engineering owing to superior biocompatibility and long term stability. Based on the idea of in situ bionics, we successfully incorporate the nano-hydroxyapatite (nHAP) and Fe3O4 nanoparticles which were prepared by in situ crystallization and freeze-drying technique into the chitosan/collagen (CS/Col) organic matrix to achieve the uniform dispersion of inorganic substrate with nanometer-scale. The in vitro results of the physicochemical and biocompatibility tests showed that CS/Col/Fe3O4/nHAP magnetic scaffold possessed superior structural and mechanical performance for cell adhesion and proliferation, as well as the osteogenic differentiation. Mineralization experiments showed better bioactive and good ability of in situ biomimetic mineralization. Moreover, from the in vivo model of SD rats' skull defects proved that the CS/Col/Fe3O4/nHAP hybrid scaffold had a better tissue compatibility and higher bone regeneration ability when implanted into the skull defects comparing to control group. Herein, the magnetic hybrid micro/nanostructured scaffold showed a potential application for bone defect repair.

Biomimetic mineralized hierarchical hybrid scaffolds based on in situ synthesis of nano-hydroxyapatite/chitosan/chondroitin sulfate/hyaluronic acid for bone tissue engineering.

Biomimetic mineralized hybrid scaffolds are widely used as natural bone substitute materials in tissue engineering by mimicking vital characters of extracellular matrix (ECM). However, the fabrication of hybrid scaffolds with suitable mechanical properties and good biocompatibility remains a challenge. To solve the problems mentioned above, biomimetic calcium phosphate mineralized organic-inorganic hybrid scaffold composed of nano hydroxyapatite (nHAP), Chitosan (CS), Chondroitin sulfate (CSA) and hyaluronic acid (HA) with hierarchical micro/nano structures was successfully developed. In this process, an efficient and easy-to-accomplish method combining in situ biomimetic synthesis with freeze-drying technology was applied. The chemical structure of the scaffolds was confirmed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Surface morphology of scaffolds was characterized by Scanning electron microscopy (SEM). The nHAP/CS/CSA/HA hybrid scaffolds with a well-distributed pore size showed suitable mechanical strength which is not only due to the addition of the nHAP but also the interaction between the positively charged CS and the negatively charged CSA and HA. Simultaneously, the biocompatibility was evaluated by the MTT cytotoxicity assay, alkaline phosphatase (ALP) activity, Hoechst 33258 fluorescence staining. All those results proved that the scaffolds possess good biocompatibility and the components added have enhanced the proliferation and differentiation of osteoblast. Thus, it can be anticipated that the in situ biomimetic mineralized nHAP/CS/CAS/HA hybrid scaffolds will be promising candidates for bone tissue engineering.

Bioinspired double polysaccharides-based nanohybrid scaffold for bone tissue engineering.

The fabrication of bone scaffolds with interconnected porous structure, adequate mechanical properties and excellent biocompatibility presents a great challenge. Herein, a hybrid nanostructured chitosan/chondroitin sulfate/hydroxyapatite (ChS/CSA/HAP) in situ composite scaffold was prepared by in situ fabrication and freeze-drying technique. The composition and morphology of scaffold were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). It proved that the low crystallinity of HAP crystals were uniformly distributed in ChS/CSA organic matrix and the nanostructured hybrid scaffold exhibited good mechanical property. The biocompatibility and in vitro bioactivity were detected by MTT-assay, maturation (alkaline phosphatase (ALP) activity), Hoechst 33258 and PI fluorescence staining. In vitro tests indicated that the hybrid scaffold not only promoted the adhesion and proliferation of osteoblasts, but also improved the growth of the osteoblasts. Therefore, it is promising for bone repair application in bone tissue engineering.

Facile preparation of biphasic-induced magnetic icariin-loaded composite microcapsules by automated in situ click technology.

This research aims to prepare the biphasic-induced magnetic composite microcapsules (BIMCM) as a promising environmental stimuli-responsive delivery vehicle to dispose the problem of drug burst effect. The paper presented a novel automated in situ click technology of magnetic chitosan/nano hydroxyapatite (CS/nHA) microcapsules. Fe3O4 magnetic nanoparticles (MNP) and nHA were simultaneously in situ crystallized by one-step process. Icariin (ICA), a plant-derived flavonol glycoside, was combined to study drug release properties of BIMCM. BIMCM were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Thermal gravimetric analysis/Differential Scanning Calorimetry(TGA/DSC) in order to reveal their component and surface morphology as well as the role of the in situ generated Fe3O4 MNP and nHA. The magnetic test showed the BIMCM were super-paramagnetic. Both in situ generated Fe3O4 MNP and nHA serve as stable inorganic crosslinkers in BIMCM to form many intermolecular crosslinkages for the movability of the CS chains. This makes ICA loaded microcapsules take on a sustained release behavior and results in the self-adjusting of surface morphology, decreasing of swelling and degradation rates. In addition, in vitro tests were systematically carried out to examine the biocompatibility of the microcapsules by MTT test, Wright-Giemsa dying assay and AO/EB fluorescent staining method. These results demonstrated that successful introduction of the in situ click Fe3O4 MNP provided an alternative strategy because of magnetic sensitivity and sustained release. As such, the novel ICA loaded biphasic-induced magnetic CS/nHA/MNP microcapsules are expected to find potential applications in drug delivery system for bone repair.

In situ strategy for bone repair by facilitated endogenous tissue engineering.

Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues.