Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

Regenerative Engineering for Knee Osteoarthritis Treatment： Biomaterials and Cell-Based Technologies

Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Extracellular matrix from human umbilical cordderived mesenchymal stem cells as a scaffold for peripheral nerve regeneration

The extracellular matrix,which includes collagens,laminin,or fibronectin,plays an important role in peripheral nerve regeneration.Recently,a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche.However,extensive clinical use of Schwann cells remains limited because of the limited origin,loss of an autologous nerve,and extended in vitro culture times.In the present study,human umbilical cord-derived mesenchymal stem cells（h UCMSCs）,which are easily accessible and more proliferative than Schwann cells,were used to prepare an extracellular matrix.We identified the morphology and function of h UCMSCs and investigated their effect on peripheral nerve regeneration.Compared with a non-coated dish tissue culture,the h UCMSC-derived extracellular matrix enhanced Schwann cell proliferation,upregulated gene and protein expression levels of brain-derived neurotrophic factor,glial cell-derived neurotrophic factor,and vascular endothelial growth factor in Schwann cells,and enhanced neurite outgrowth from dorsal root ganglion neurons.These findings suggest that the h UCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

In vitro Characterization of PBLG-g-HA/PLLA Nanocomposite Scaffolds

The purpose of the present study was to synthesize a new composites scaffold containing poly（γ-benzyl-L-glutamate） modified hydroxyapatite/（poly（L-lactic acid））（PBLG-g-HA/PLLA） and to investigate their in vitro behaviour on bone mesenchymal stromal cells（BMSCs）. The results demonstrated that BMSC proliferation was signifi cantly increased on PBLG-g-HA/PLLA scaffolds after 3 and 7 days post seeding when compared to PLLA and HA/PLLA scaffolds. The in vitro osteogenic differentiation also favoured the composite PBLG-g-HA/PLLA scaffolds when compared to controls by signifi cantly increasing Runx2, ALP or osteocalcin mRNA expression as assessed by real-time PCR. The results illustrate the potential of PBLG-g-HA/PLLA scaffolds for bone tissue engineering applications. And the in vivo testing further confi rms the PBLG-gHA/PLLA scaffolds＇ potentioal for healing critical bone defects.

Modelling the development of biological structures displaying longitudinal geometries in vitro:culturing pluripotent stem cells on plasma-treated,growth factor-coupled polycaprolactone fibres

Many biological structures such as nerves,blood and lymphatic vessels,and muscle fibres exhibit longitudinal ge-ometries with distinct cell types extending along both the length and width of internal linear axes.Modelling these three-dimensional structures in vitro is challenging:the best-defined stem-cell differentiation systems are mono-layer cultures or organoids using pluripotent stem cells.Pluripotent stem cells can differentiate into functionally mature cells depending on the signals received,holding great promise for regenerative medicine.However,the integration of in vitro differentiated cell types into diseased tissue remains a challenge.Engineered scaffolds can bridge this gap if the appropriate signalling systems are incorporated into the scaffold.Here,we have taken a biomimicry approach to generate longitudinal structures in vitro.In this approach,mouse embryonic stem cells are directed to differentiate to specific cell types on the surface of polycaprolactone(PCL)fibres treated by plasma-immersion ion implantation and to which with lineage-specifying molecules have been covalently im-mobilised.We demonstrate the simplicity and utility of our method for efficiently generating high yields of the following cell types from these pluripotent stem cells:neurons,vascular endothelial cells,osteoclasts,adipocytes,and cells of the erythroid,myeloid,and lymphoid lineages.Strategically arranged plasma-treated scaffolds with differentiated cell types could ultimately serve as a means for the repair or treatment of diseased or damaged tissue.

Biomedical applications of magneto-responsive scaffolds

Stimuli-responsive biomaterials, capable of responding on-demand to changes in their local environment, have become a subject of interest in the field of regenerative medicine. Magneto-responsive biomaterials, which can be manipulated spatiotemporally via an external magnetic field, have emerged as promising candidates as active scaffolds for advanced drug delivery and tissue regeneration applications. These specialized biomaterials can be synthesized by physically and/or chemically incorporating magnetic nanoparticles into the biomaterial structure. However, despite their promising impact on the future of regenerative medicine, magneto-responsive biomaterials still have several limitations that need to be overcome before they can be implemented clinically in a reliable manner, as predicting their behavior and biocompatibility remains an ongoing challenge. This review article will focus on discussing the current fabrication methods used to synthesize magneto-responsive materials, efforts to predict and characterize magneto-responsive biomaterial behavior, and the application of magneto-responsive biomaterials as controlled drug delivery systems, tissue engineering scaffolds, and artificial muscles.

Preparation and Characterization of Hydroxyapatite-Coated Selenium Nanoparticles and their Interaction with Osteosarcoma(SaOS-2) Cells

Nanotechnology has taken a firm step to revolutionize the field of orthopedic implants. Current research on bone implants focuses to develop implants with multifaceted functions viz., osteoinduction, chemoprevention, antimicrobial action etc., especially for cancerous bone resection. The objective of the present study was to synthesize a novel composite for bone implants, possessing the above properties. Selenium was selected owing to its chemopreventive and chemotherapeutic properties. Hydroxyapatite was selected owing to its bioactivity and similarity in composition to bone mineral properties. Selenium nanoparticles were prepared by chemical reduction method and coated with hydroxyapatite.Hydroxyapatite-coated selenium nanoparticle（HASnp） was characterized physico-chemically using fourier transform infrared spectroscopy, X-ray diffractometry, scanning electron microscope, and energy-dispersive X-ray spectroscopy.HASnp was analysed in vitro using SaOS-2 cell line. Enhanced cell proliferation and alkaline phosphatase activity were observed in HASnp-treated cells. The results indicate that HASnp is highly suitable for the use in orthopedic applications.