High-strength mineralized collagen artificial bone

Mineralized collagen （MC） is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal＇s cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in v/vo implantation assay demonstrated good biocompatibility of the material, and in v/vo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load- bearing sites.

Strength and fatigue properties of three-step sintered dense nanocrystal hydroxyapatite bioceramics

Dense hydroxyapatite （HA） ceramic is a promising material for hard tissue repair due to its unique physical properties and biologic properties. However, the brittleness and low compressive strength of traditional HA ceramics limited their applications, because previous sintering methods produced HA ceramics with crystal sizes greater than nanometer range. In this study, nano-sized HA powder was employed to fabricate dense nanocrystal HA ceramic by high pressure molding, and followed by a three-step sintering process. The phase composition, microstructure, crystal dimension and crystal shape of the sintered ceramic were examined by X-ray diffraction （XRD） and scanning electron microscopy （SEM）. Mechanical properties of the HA ceramic were tested, and cytocompatibility was evaluated. The phase of the sintered ceramic was pure HA, and the crystal size was about 200 nm. The compressive strength and elastic modulus of the HA ceramic were comparable to human cortical bone, especially the good fatigue strength overcame brittleness of traditional sintered HA ceramics. Cell attachment experiment also demonstrated that the ceramics had a good cytocompatibility.

Poly(methyl methacrylate) bone cement composited with mineralized collagen for osteoporotic vertebral compression fractures in extremely old patients

To examine the clinical effects of a new bone cement composed of poly(methyl methacrylate)(PMMA)and mineralized collagen(MC)compared with pure PMMA bone cement in treating osteoporotic vertebral compression fractures(OVCFs)in patients aged over 80.In all,32 cases using pure PMMA bone cement and 31 cases using MC-modified PMMA(MC-PMMA)bone cement for OVCFs between June 2014 and March 2016 were screened as PMMA group and MC-PMMA group,respectively,with an average age of over 80.The operation duration,intraoperative blood loss,hospital stay,oswestry disability index(ODI),visual analogue scale(VAS),anterior vertebral height(AVH),intermediate vertebral height(IVH)and posterior vertebral height(PVH)of injured vertebrae,vertebral computed tomography value,re-fracture rate of adjacent vertebrae,correction rate of spinal kyphotic angle and wedge-shaped vertebra angle and surgical complications were compared between the two groups.In the early post-operative period,the VAS,ODI,AVH and IVH in MC-PMMA group were comparable to those in the traditional PMMA group.Moreover,the MC-PMMA group showed better effects compared with the PMMA group 12months after surgery.Thus,this new bone cement has superior clinic effects in the long term.

Various fates of neuronal progenitor cells observed on several different chemical functional groups

Neuronal progenitor cells cultured on gold-coated glass surfaces modified by different chemical functional groups, including hydroxyl （-OH）, carboxyl （COOH）, amino （-NH2）, bromo （-Br）, mercapto （-SH）, - Phenyl and methyl （-CH3）, were studied here to investigate the influence of surface chemistry on the cells＇ adhesion, morphology, proliferation and functional gene expression. Focal adhesion staining indicated in the initial culture stage cells exhibited morphological changes in response to different chemical functional groups. Cells cultured on -NH2 grafted surface displayed focal adhesion plaque and flattened morphology and had the largest contact area. However, their counter parts on -CH3 grafted surface displayed no focal adhesion and rounded morphology and had the smallest contact area. After 6 days culture, the proliferation trend was as follows： NH2〉 SH〉-COOH〉 Phenyl〉 Br〉 OH〉-CH3. To deter- mine the neural functional properties of the cells affected by surface chemistry, the expression of glutamate decarboxylase （GAD67）, nerve growth factor （NGF） and brain- derived neurotrophic factor （BDNF） were characterized. An increase of GAD67 expression was observed on - NH2, -COOH and -SH grafted surfaces, while no increase in NGF and BDNF expression was observed on any chemical surfaces. These results highlight the importance of surface chemistry in the fate determination of neuronal progenitor cells, and suggest that surface chemistry must be considered in the design of biomaterials for neural tissue engineering.

Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration

Repairing damage in the craniofacial skeleton is challenging.Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis.Here,we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor(VEGF)for implantation into animal models of mandibular defects.BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular.Animals were divided into(i)controls with no growth factors;(ii)BMP-2 alone;or(iii)BMP-2 and VEGF combined.CT and hisomputed tomography and histological staining were performed to assess bone repair.New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced.This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.

Scaffolds for central nervous system tissue engineering

Traumatic injuries to the brain and spinal cord of the central nervous system （CNS） lead to severe and permanent neurological deficits and to date there is no universally accepted treatment. Owing to the profound impact, extensive studies have been carried out aiming at reducing inflammatory responses and overcoming the inhibitory environment in the CNS after injury so as to enhance regeneration. Artificial scaffolds may provide a suitable environment for axonal regeneration and functional recovery, and are of particular importance in cases in which the injury has resulted in a cavitary defect. In this review we discuss development of scaffolds for CNS tissue engineering, focusing on mechanism of CNS injuries, various biomaterials that have been used in studies, and current strategies for designing and fabricating scaffolds.

Cancer cell proliferation controlled by surface chemistry in its microenvironment

Hepatoma cells （Hepg2s） as typical cancer cells cultured on hydroxyl （-OH） and methyl （- CH3） group surfaces were shown to exhibit different proliferation and morphological changes. Hepg2s cells on OH surfaces grew much more rapidly than those on -CH3 surfaces. Hepg2s cells on -OH surfaces had the larger contact area and the more flattened morphology, while those on CH3 surfaces exhibited the smaller contact area and the more rounded morphology. After 7 days of culture, the migration of Hepg2s cells into clusters on the CH3 surfaces behaved significantly slower than that on the OH surfaces. These chemically modified surfaces exhibited regulation of Hepg2s cells on proliferation, adhesion, and migration, providing a potential treatment of liver cancer.

A new rabbit model of implant-related biofilm infection： development and evaluation

This study is to establish a rabbit model for human prosthetic joint infection and biofiim formation. Thirty-two healthy adult rabbits were randomly divided into four groups and implanted with stainless steel screws and ultra-high molecular weight polyethylene （UHMWPE） washers in the non-articular surface of the femoral lateral condyle of the right hind knees. The rabbit knee joints were inoculated with 1 mL saline containing 0, 102, 103, 104 CFU of Staphylococcus epidermidis （S. epidermidis） isolated from the patient with total knee arthroplasty （TKA） infection, respectively. On the 14th postoperative day, the UHMWPE washers from the optimal 103 CFU group were further examined. The SEM examination showed a typical biofilm construction that circular S. epidermidis were embedded in a mucous-like matrix. In addition, the LCSM examination showed that the biofilm consisted of the polysaccharide stained bright green fluorescence and S. epidermidis radiating red fluorescence. Thus, we successfully create a rabbit model for prosthetic joint infection and biofilm formation, which should be valuable for biofilm studies.

Recent progress in injectable bone repair materials research

Minimally invasive injectable self-setting materials are useful for bone repairs and for bone tissue regeneration in situ. Due to the potential advantages of these materials, such as causing minimal tissue injury, nearly no influence on blood supply, easy operation and negligible postoperative pain, they have shown great promises and successes in clinical applications. It has been proposed that an ideal injectable bone repair material should have features similar to that of natural bones, in terms of both the microstructure and the composition, so that it not only provides adequate stimulus to facilitate cell adhesion, proliferation and differentiation but also offers a satisfactory biological environment for new bone to grow at the implantation site. This article reviews the properties and applications of injectable bone repair materials, including those that are based on natural and synthetic polymers, calcium phosphate, calcium phosphate/ polymer composites and calcium sulfate, to orthopedics and bone tissue repairs, as well as the progress made in biomimetic fabrication of injectable bone repair materials.

Biomaterials for reconstruction of cranial defects

Reconstruction of cranial defect is commonly performed in neurosurgical operations. Many materials have been employed for repairing cranial defects. In this paper, materials used for cranioplasty, including autografts, allografts, and synthetic biomaterials are comprehensively reviewed. This paper also gives future perspective of the materials and development trend of manufacturing process for cranioplasty implants.

Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells

Cellular strategies remain a crucial component in bone tissue engineering （BTE）. So far, the outcome of cell-based strategies from initial clinical trials is far behind compared to animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the Ussue-engineered constructs. Cocultures, by introducing angiogenic cells into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, pre-clinical studies demonstrated that cocultures enhance vascularization and bone formation compared to monocultures. However, there has been no report on the application of cocultures in clinics. Therefore, this mini-review aims to provide an overview regarding （i） critical parameters in cocultures and the outcomes of cocultures compared to monocultures in the currently available pre-clinical studies using human mesenchymal stem cells implanted in orthotopic animal models; and （ii） the usage of monocultures in clinical application in BTE.

Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

CT： Artificial tissue engineering scaffods can potentially provide supportand guidance for the regrowth of severed axons following nerve injury. In this study a hybrid biomaterial composed of alginate and hyaluronic acid （HA） was synthesized characterized in terms of its suitability for covalent modification, biocompatibility fir living Schwann cells and feasibility to construct three dimensional （3D） Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calcium ions that ionically crosslink alginate.Amide formation was found to be dependent on the concentrations of cabodiimide and calclum chloride. The double-crosslinked composite hydrogels display blocompatibllity that is comparable to simple HA hydrogels, allowing for Schwann cell survival and significant difference was found between composite hydrogels made from different of alginate and HA. A 3D BioPIotterTM rapid prototyping system was used to fabricats 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated ;from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.

Tumor-suppressor effects of chemical functional groups in an in vitro co-culture system

Liver normal cells and cancer cells co-cultured on surfaces modified by different chemical functional groups, including mercapto （-SH）, hydroxyl （-OH） and methyl （-CHz） groups. The results showed that different cells exhibited changes in response to different surfaces. Normal cells on -SH surface exhibited the smallest contact area with mostly rounded morphology, which led to the death of cancer cells, while cancer cells could not grow on -CH3 groups, which also died. In the co-culture system, the -CH3 group exhibited its unique effect that could trigger the death of cancer cells and had no effects on normal cells. Our findings provide useful information on strategies for the design of efficient and safe regenerative medicine materials.

Important Topics in the Future of Tissue Engineering

Over 150 participants from around the world congregated on the beautiful island of Kos—home of Hippocrates,Father of Medicine—from June 20 to June 25,2014,to share their research findings and engage in dialogue pertaining to progress in tissue engineering.Since the field’s inception,we have witnessed its astonishing development over the past 30 years and the groundbreaking work stemming from both laboratory and clinical settings.Despite continuously evolving concepts and strategies,the essential ingredients of scaffolds,cells and growth factors remain to be explored further.

Editorial

In recent years,biomaterials have advanced into a burgeoning interdisciplinary research field combining traditional material science,engineering,biology and medicine.Over the last half-century,many types of lifeless materials such as metals,ceramics and polymers have become‘bio’-materials,making their way into the fabrication of medical devices for the repair or replacement of damaged or deteriorating human tissues and organs.As we proceed into this new century,this process has accelerated.In the last decade alone,the integration of advances in materials and life sciences with cutting-edge medical sciences and nanotechnologies has driven biomaterial research into an explosive phase.