High biocompatible polyacrylamide hydrogels fabricated by surface mineralization for subchondral bone tissue engineering.

The subchondral bone is an important part of cartilage which contains a large amount of hydroxyapatite. The mineral components of subchondral bone is the key factor which determines the biomechanical strength, and then affects the biological function of articular cartilage. Here, a mineralized polyacrylamide (PAM-Mineralized) hydrogel with good ALP activity, cell adhesion and biocompatibility was fabricated for subchondral bone tissue engineering. The micromorphology, composition and mechanical properties of PAM and PAM-Mineralized hydrogels were studied. The PAM hydrogels showed a porous structure, while the PAM-Mineralized hydrogels had well-distributed layers of hydroxyapatite mineralization on the surface. The XRD results show that the characteristic peak of hydroxyapatite (HA) was measured in PAM-Mineralized, indicating that the main component of the mineralized structure formed on the surface of the hydrogel after mineralization is HA. The formation of HA ectively decreased the rate of equilibrium swelling of the PAM hydrogel, with PAM-M reaching swelling equilibrium at 6 h. Meanwhile, compressive strength of PAM-Mineralized hydrogel (moisture state) reached 290 ± 30 kPa, compressive modulus reached 130 ± 4 kPa. PAM-Mineralized hydrogels did not affect the growth and proliferation of MC3T3-E1 cells. Surface mineralization of PAM hydrogel could significantly improve osteogenic differentiation of MC3T3-E1 cells. These results showed that PAM-Mineralized hydrogel could possess potential application in the field of subchondral bone tissue engineering.

A facile method to fabricate high performance PVA/PAA-AS hydrogel via the synergy of multiple hydrogen bonding and Hofmeister effect.

Hydrogels are widely used in biomedical engineering, which often require matched mechanical properties to meet specific demands. Recently, numerous research studies have contributed to tissue engineering hydrogels by soaking strategies to obtain designed properties. Herein, a strategy to fabricate poly(vinyl alcohol)/poly(acrylic acid)-ammonium sulfate (PVA/PAA-AS) hydrogel by successively soaking an aqueous PAA solution and (NH4)2SO4 solution based on the synergy of multiple hydrogen bonding and Hofmeister effect is reported, which exhibits remarkable comprehensive mechanical properties: rigidity (elastic modulus: 0.7-3.6 MPa), strength at break (tensile stress: 3.2-12.0 MPa; strain 320-650%), and toughness (fracture energy: 4.5-30.0 MJ m-3). Besides, PVA/PAA-AS hydrogel with unique spring-like microstructure exhibited super-resilience in 30% strain range by energy-transforming mechanism. Compared with pure PVA hydrogel, PVA/PAA-AS hydrogel has the equal excellent cytocompatibility. Therefore, PVA/PAA-AS hydrogel with high strength, modulus, toughness, super-resilience and excellent biocompatibility has potential applications in the soft tissue engineering field such as muscles, tendons, and ligaments.

Preparation of PAA/PAM/MXene/TA hydrogel with antioxidant, healable ability as strain sensor.

Conductive hydrogels based on MXene have gained more attention due to the excellent conductive property and biocompatibility. At present, they have great potential in electronic skins, personally healthcare monitoring and human motion sensing. However, MXene are prone to be oxidized due to the abundant hydroxyls, which results in the unstable conductive property of hydrogel. To improve the shortcoming, conductive PAA/PAM/MXene/TA hydrogel was prepared, in which the introduction of TA can prevent MXene from oxidation owing to the great deal of pyrogallol groups. Mechanical tests showed that the tensile strength, toughness and elongation at break of PAA/PAM/MXene/TA hydrogel are 0.251 ± 0.05 MPa, 0.895 ± 0.16 MJ/m3 and 560.82 ± 19.56%, respectively, indicating the hydrogel possess good stretchability. In addition, the MXene and TA were introduced into hydrogel through hydrogen bonds, which endow the hydrogel with good restorability and self-healing property. Resistance variation-strain curves demonstrated that the introduction of MXene endue the hydrogel with appreciable sensing performances. Moreover, in vitro cytotoxicity assay indicated that the hydrogel has good biocompatibility. In conclusion, PAA/PAM/MXene/TA hydrogel has great potential in flexible wearable sensor field.

Bone-like hydroxyapatite anchored on alginate microspheres for bone regeneration.

Inspired by the initial mineralization process in bone matrix vesicles (MVs), we used Dulbecco's Modified Eagle's Medium (DMEM) to establish the similar physiological environment to that in MVs for biomimetic mineralization on alginate (ALG) microspheres. The results showed that HA crystals were firstly formed and anchored on the membrane of microspheres like the initial deposition of hydroxyapatite crystals inside MVs. With the continuous growth and accumulation of mineral crystals, HA coating was finally formed on ALG microspheres. The mineralized ALG microspheres (M-ALG microspheres) show good biocompatibility and osteogenic performance. The HA coating is also conducive to the active migration of osteoblasts to the surface of M-ALG microspheres. Collectively, bone-like HA crystals anchored on ALG microspheres may provide a good prospect to promote the repair of bone defects.

Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine.

Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.

Core-Shell Nanofibers with a Shish-Kebab Structure Simulating Collagen Fibrils for Bone Tissue Engineering.

The repair of bone defects is one of the great challenges facing modern orthopedics clinics. Bone tissue engineering scaffold with a nanofibrous structure similar to the original microstructure of a bone is beneficial for bone tissue regeneration. Here, a core-shell nanofibrous membrane (MS), MS containing glucosamine (MS-GLU), MS with a shish-kebab (SK) structure (SKMS), and MS-GLU with a SK structure (SKMS-GLU) were prepared by micro-sol electrospinning technology and a self-induced crystallization method. The diameter of MS nanofibers was 50-900 nm. Contact angle experiments showed that the hydrophilicity of SKMS was moderate, and its contact angle was as low as 72°. SK and GLU have a synergistic effect on cell growth. GLU in the core of MS was demonstrated to obviously promote MC3T3-E1 cell proliferation. At the same time, the SK structure grown on MS-GLU nanofibers mimicked natural collagen fibers, which facilitated MC3T3-E1 cell adhesion and differentiation. This study showed that a biomimetic SKMS-GLU nanofibrous membrane was a promising tissue engineering scaffold for bone defect repair.

Application of electrospun nanofibers in bone, cartilage and osteochondral tissue engineering.

Tissue damage related to bone and cartilage is a common clinical disease. Cartilage tissue has no blood vessels and nerves. The limited cell migration ability results in low endogenous healing ability. Due to the complexity of the osteochondral interface, the clinical treatment of osteochondral injury is limited. Tissue engineering provides new ideas for solving this problem. The ideal tissue engineering scaffold must have appropriate porosity, biodegradability and specific functions related to tissue regeneration, especially bioactive polymer nanofiber composite materials with controllable biodegradation rate and appropriate mechanical properties have been getting more and more research. The nanofibers produced by electrospinning have high specific surface area and suitable mechanical properties, which can effectively simulate the natural extracellular matrix (ECM) of bone or cartilage tissue. The composition of materials can affect mechanical properties, plasticity, biocompatibility and degradability of the scaffold, thereby further affect the repair efficiency. This article reviews the characteristics of polymer materials and the application of its electrospun nanofibers in bone, cartilage and osteochondral tissue engineering.

Uniform Fe3O4/Gd2O3-DHCA nanocubes for dual-mode magnetic resonance imaging.

The multimodal magnetic resonance imaging (MRI) technique has been extensively studied over the past few years since it offers complementary information that can increase diagnostic accuracy. Simple methods to synthesize contrast agents are necessary for the development of multimodal MRI. Herein, uniformly distributed Fe3O4/Gd2O3 nanocubes for T 1-T 2 dual-mode MRI contrast agents were successfully designed and synthesized. In order to increase hydrophilicity and biocompatibility, the nanocubes were coated with nontoxic 3,4-dihydroxyhydrocinnamic acid (DHCA). The results show that iron (Fe) and gadolinium (Gd) were homogeneously distributed throughout the Fe3O4/Gd2O3-DHCA (FGDA) nanocubes. Relaxation time analysis was performed on the images obtained from the 3.0 T scanner. The results demonstrated that r 1 and r 2 maximum values were 67.57 ± 6.2 and 24.2 ± 1.46 mM-1·s-1, respectively. In vivo T 1- and T 2-weighted images showed that FGDA nanocubes act as a dual-mode contrast agent enhancing MRI quality. Overall, these experimental results suggest that the FGDA nanocubes are interesting tools that can be used to increase MRI quality, enabling accurate clinical diagnostics.

High strength polyvinyl alcohol/polyacrylic acid (PVA/PAA) hydrogel fabricated by Cold-Drawn method for cartilage tissue substitutes.

Poly (vinyl alcohol) (PVA) hydrogel has been considered as promising cartilage replacement materials due to its excellent characteristics such as high water content, low frictional behavior and excellent biocompatibility. However, lack of sufficient mechanical properties and cytocompatibility are two key obstacles for PVA hydrogel to be applied as cartilage substitutes. Herein, Polyacrylic acid (PAA) has been introduced into PVA hydrogel to balance these problems. Compared with pure PVA hydrogel, PVA/PAA hydrogel has the equal excellent biocompatibility, and its cell adhesion is significantly improved. In order to further improve the mechanical properties of hydrogels, Cold-Drawn treatment of hydrogels is performed in this paper. Compared to pure 12% PVA hydrogel, 40.8-fold, 50.8-fold, and 46.8-fold increase in tensile strength, tensile modulus, and toughness, respectively, which can be obtained from 12% PVA/PAA Cold-Drawn hydrogel. These biocompatible composite hydrogels have a great application potential as cartilage tissue substitutes.