Frontiers of Materials Science (v.8, #1)

Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a highperformance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.
Keywords: electrospinning; monocomponent; multicomponent; scaffold; core-shell; drug; biomolecule; growth factor; controlled release

Increasing evidence shows that magnetic fields and magnetic responsive scaffolds can play unique roles in promoting bone repair and regeneration. This article addresses the synergistic effects of magnetic scaffolds in response to external magnetic fields on the bone regeneration in situ. Additionally, the exploration of using magnetic scaffolds as tools in the bone implant fixation, local drug delivery and mimicking microenvironment of stem cell differentiation are introduced. We also discussed possible underlying mechanisms and perspectives of magnetic responsive scaffolds in the bone repair and regeneration.
Keywords: bone repair; magnetic scaffold; magnetic field; physical stimulation

Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells by Jin-Ling Ma; Jeroen J. J. P. van den Beucken; Ju-Li Pan; Fu-Zhai Cui; Su Chen (32-38).
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 tissue-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.
Keywords: mesenchymal stem cell (MSC); endothelial cell (EC); coculture; vascularization; tissue regeneration

Conducting polypyrrole in tissue engineering applications by Zhong-Bing Huang; Guang-Fu Yin; Xiao-Ming Liao; Jian-Wen Gu (39-45).
Polypyrrole (PPy), the earliest prepared conducting polymer, has good biocompatibility, easy synthesis and flexibility in processing. Compared with metal and inorganic materials, doped PPy has better mechanical match with live tissue, resulting in its many applications in biomedical field. This mini-review presents some information on specific PPy properties for tissue engineering applications, including its synthesis, doping, bio-modification. Although some challenges and unanswered problems still remain, PPy as novel biomaterial has promoted the development tissue engineering for its clinical application in the future.
Keywords: conducting polypyrrole; doping; modification; tissue engineering

Preparation and application of highly porous aerogel-based bioactive materials in dentistry by Andrea Kuttor; Melinda Szalóki; Tünde Rente; Farkas Kerényi; József Bakó; István Fábián; István Lázár; Attila Jenei; Csaba Hegedüs (46-52).
In this study, the possibility of preparation and application of highly porous silica aerogel-based bioactive materials are presented. The aerogel was combined with hydroxyapatite and β-tricalcium phosphate as bioactive and osteoinductive agents. The porosity of aerogels was in the mesoporous region with a maximum pore diameter of 7.4 and 12.7 nm for the composite materials. The newly developed bioactive materials were characterized by scanning electron microscopy. The in vitro biological effect of these modified surfaces was also tested on SAOS-2 osteogenic sarcoma cells by confocal laser scanning microscopy.
Keywords: aerogel; sol-gel technique; bioactive material; SAOS-2 cell

High-strength mineralized collagen artificial bone by Zhi-Ye Qiu; Chun-Sheng Tao; Helen Cui; Chang-Ming Wang; Fu-Zhai Cui (53-62).
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 vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.
Keywords: mineralized collagen (MC); high strength; biomimetic mineralization; cold compression molding

In vitro biocompatibility evaluation of silk-fibroin/polyurethane membrane with cultivation of HUVECs by Mei Zhou; Wei-Ci Wang; Yong-Gui Liao; Wen-Qi Liu; Miao Yu; Chen-Xi Ouyang (63-71).
In order to investigate the in vitro biocompatibility of a novel polyurethane (PU) membrane modified by incorporation of superfine silk-fibroin powder (SFP), which was prepared for small-diameter vascular grafts, with the cultivation of human umbilical vein endothelial cells (HUVECs), PU and SFP were mixed with the ratios of 9:1, 7:3, 5:5, 3:7 (PU:SFP) to make four composite materials. Unmodified PU and polytetrafluoroethylene (PTFE) were added as control groups. CCK-8 assay was used to evaluate the cytotoxicity of these biomaterials. Data were processed using SPSS, and P < 0.05 was considered to be statistically significant. Adherence and spreading of HUVECs on the surface of specimens was observed using direct contact cultivation. The toxicity ratings of the novel composites were grade 0–1, which is in the acceptable range. In all the experimental groups except control, SFP/PU with ratio of 1:9 had the least cytotoxicity property, and more content of SFP in the composite showed no improvement of the biocompatibility. HUVECs strongly attached to and grew on the surface of the biomaterials, and proliferated rapidly. The proliferation ability increased with increased proportion of SFP; however the cell quantity on the surface of the materials decreased when the proportion of SFP was equal to or larger than that of PU in the composite. It is concluded that this novel material has excellent cellular affinity with no cytotoxicity to HUVECs. Adding SFP gives PU better biocompatibility, while further research on optimum blend ratios is still needed.
Keywords: polyurethane (PU); silk-fibroin (SF); small diameter vascular graft; biocompatibility; human umbilical vein endothelial cell (HUVEC)

Time-sequential changes of differentially expressed miRNAs during the process of anterior lumbar interbody fusion using equine bone protein extract, rhBMP-2 and autograft by Da-Fu Chen; Zhi-Yu Zhou; Xue-Jun Dai; Man-Man Gao; Bao-Ding Huang; Tang-Zhao Liang; Rui Shi; Li-Jin Zou; Hai-Sheng Li; Cody Bünger; Wei Tian; Xue-Nong Zou (72-86).
The precise mechanism of bone regeneration in different bone graft substitutes has been well studied in recent researches. However, miRNAs regulation of the bone formation has been always mysterious. We developed the anterior lumbar interbody fusion (ALIF) model in pigs using equine bone protein extract (BPE), recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS), and autograft as bone graft substitute, respectively. The miRNA and gene expression profiles of different bone graft materials were examined using microarray technology and data analysis, including self-organizing maps, KEGG pathway and Biological process GO analyses. We then jointly analyzed miRNA and mRNA profiles of the bone fusion tissue at different time points respectively. Results showed that miRNAs, including let-7, miR-129, miR-21, miR-133, miR-140, miR-146, miR-184, and miR-224, were involved in the regulation of the immune and inflammation response, which provided suitable inflammatory microenvironment for bone formation. At late stage, several miRNAs directly regulate SMAD4, Estrogen receptor 1 and 5-hydroxytryptamine (serotonin) receptor 2C for bone formation. It can be concluded that miRNAs play important roles in balancing the inflammation and bone formation.
Keywords: miRNA; bone protein extract (BPE); recombinant human bone morphogenetic protein-2 (rhBMP-2); autograft

Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture by Ke-Bin Liu; Kui Huang; Yu Teng; Yan-Zheng Qu; Wei Cui; Zhen-Fei Huang; Ting-Fang Sun; Xiao-Dong Guo (87-94).
Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 (n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 (n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination (p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation (p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.
Keywords: comminuted distal radius fracture; bone graft; augmentation

Synthesis, characterization and biological evaluation of poly [LA-co-(Glc-alt-Lys)] for nerve regeneration scaffold by Yi-Xia Yin; Ji-Ling Yi; Li-Juan Xie; Qiong-Jiao Yan; Hong-Lian Dai; Shi-Pu Li (95-101).
A novel nerve repairing material poly [LA-co-(Glc-alt-Lys)] (PLGL) was synthesized. The viability and growth of Schwann cells (SCs) co-cultured with poly (D, Llactic acid) (PDLLA) films (control group) and PLGL films were evaluated by MTTassay and SEM observation. Then, contact angle measurement, histological assessment and enzyme-linked immunosorbent assay (ELISA) testing on inflammatory-related cytokines such as IL-10 and TGF-β1 were performed. The results showed that, compared with PDLLA, PLGL films possesses better hydrophilicity, biocompatibility, degradation property and less inflammatory reaction. The present study indicated that PLGL scaffolds would meet the requirements of artificial nerve scaffold and have a potential application in the fields of nerve regeneration.
Keywords: Schwann cell (SC); poly [LA-co-(Glc-alt-Lys)] (PLGL); implantation; inflammatory factor; biocompatibility

Conductive Au-biopolymer composites have promising applications in tissue engineering such as nerve tissue regeneration. In this study, silk fibroin nanofibers were formed in aqueous solution by regulating silk self-assembly process and then used as template for Au nanowire fabrication. We performed the synthesis of Au seeds by repeating the seeding cycles for several times in order to increase the density of Au seeds on the nanofibers. After electroless plating, densely decorated Au seeds grew into irregularly shaped particles following silk nanofiber to fill the gaps between particles and finally form uniform continuous nanowires. The conductive property of the Au-silk fibroin nanowires was studied with current-voltage (I–V) measurement. A typical ohmic behavior was observed, which highlighted their potential applications in nerve tissue regeneration.
Keywords: silk; Au nanowire; electrical conductivity; biological device