Degradation rate is an important index for evaluating biomaterials. The authors' aim was to determine whether the degradation rate of biomaterials is different in distinct tissues and to clarify the underlying mechanism of degradation. The collagen-chitosan (CG-CS) composite scaffolds were prepared using freeze-drying technology. The porosity, water absorption and swelling ratio of the scaffolds were tested in vitro. The scaffolds were implanted into the subcutis, spinal cord and brain tissues of SD rats, the rate of degradation was assessed by continuous monitoring of weight loss, the pathological changes of target areas were observed by histological staining, and matrix metalloproteinase 9 (MMP-9) and lysozyme were detected at the rapid stage of degradation of the scaffolds. Physical and chemical property testing confirmed that CG-CS composite scaffold components can meet the biological requirements of in vivo transplantation. The in vivo experimental results showed that the scaffolds were completely absorbed in the subcutis at 12 days, the scaffolds in the spinal cord and brain groups exhibited progressive mass loss starting from the 3rd week, and a substantial fraction of the scaffold was degraded at 12 weeks. HE staining found that compared with the spinal cord and brain groups, macrophages and capillaries appeared earlier in the subcutis group, and the number was significantly higher (P < 0.05). Western blot analysis showed that the MMP-9 and lysozyme levels in the subcutis were higher than those in the spinal cord and brain (P < 0.05). The results of in vivo experiments demonstrated that the CG-CS scaffold has good biocompatibility and biodegradability, while the rate of degradation was significantly different between the three tissues at the same time point. Macrophage behavior and vascularization in different parts of the body may result in control over the balance of degradation and reconstruction.

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.

Effective treatments promoting axonal regeneration and functional recovery for spinal cord injury (SCI) are still in the early stages of development. Most approaches have been focused on providing supportive substrates for guiding neurons and overcoming the physical and chemical barriers to healing that arise after SCI. Although collagen has become a promising natural substrate with good compatibility, its low mechanical properties restrict its potential applications. The mechanical properties mainly rely on the composition and pore structure of scaffolds. For the composition of a scaffold, we used heparin sulfate to react with collagen by crosslinking. For the structure, we adopted a three-dimensional (3D) printing technology to fabricate a scaffold with a uniform pore distributions. We observed that the internal structure of the scaffold printed with a 3D bioprinter was regular and porous. We also found that both the compression modulus and strengths of the scaffold were significantly enhanced by the collagen/heparin sulfate composition compared to a collagen scaffold. Meanwhile, the collagen/heparin sulfate scaffold presented good biocompatibility when it was co-cultured with neural stem cells in vitro. We also demonstrated that heparin sulfate modification significantly improved bFGF immobilization and absorption to the collagen by examining the release kinetics of bFGF from scaffolds. Two months after implantating the scaffold into transection lesions in T10 of the spinal cord in rats, the collagen/heparin sulfate group demonstrated significant recovery of locomotor function and according to electrophysiological examinations. Parallel to functional recovery, collagen/heparin sulfate treatment further ameliorated the pathological process and markedly increased the number of neurofilament (NF) positive cells compared to collagen treatment alone. These data suggested that a collagen/heparin sulfate scaffold fabricated by a 3D bioprinter could enhance the mechanical properties of collagen and provide continuous guidance channels for axons, which would improve the neurological function after SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1324-1332, 2017.

Long-term exposure to fine particulate matter (PM2.5) may cause adverse pregnancy outcomes but the mechanisms are not clear. Our research confirms that PM2.5 induced DNA damage, and inhibited cell proliferation in HTR-8/SVneo cells, presenting in a dose- and time-dependent manners. Using quantitative proteomics, the 182 and 486 differentially expressed proteins in cells treated with 120μgml−1 PM2.5 for 24 and 48h were involved in many critical biological processes, including of cell proliferation, response to DNA damage, regulation of small GTPase mediated signal transduction, and etc. Further validation indicated that PM2.5 blocked the cell cycle at the G2/M phase through activation of the ATR-Cyclin E1/Cdk6 pathway, and it reduced the migration and invasion by upregulating TIMP1 and TIMP2 expression and downregulating Collagen I expression. Our findings were consistent with the observed effects of PM2.5 on cell cycle arrest and inhibition of migration and invasion in human extravillous trophoblast.

Mesenchymal stem cells (MSCs), which are regarded as promising candidates for cell replacement therapies, are able to regulate immune responses after traumatic brain injury (TBI). Secondary immune response following the mechanical injury is the essential factor leading to the necrosis and apoptosis of neural cells during and after the cerebral edema has subsided and there is lack of efficient agent that can mitigate such neuroinflammation in the clinical application. By means of three molecular pathways (prostaglandin E2 (PGE2), tumor-necrosis-factor-inducible gene 6 protein (TSG-6), and progesterone receptor (PR) and glucocorticoid receptors (GR)), MSCs induce the activation of macrophages/microglia and drive them polarize into the M2 phenotypes, which inhibits the release of pro-inflammatory cytokines and promotes tissue repair and nerve regeneration. The regulation of MSCs and the polarization of macrophages/microglia are dynamically changing based on the inflammatory environment. Under the stimulation of platelet lysate (PL), MSCs also promote the release of pro-inflammatory cytokines. Meanwhile, the statue of macrophages/microglia exerts significant effects on the survival, proliferation, differentiation and activation of MSCs by changing the niche of cells. They form positive feedback loops in maintaining the homeostasis after TBI to relieving the secondary injury and promoting tissue repair. MSC therapies have obtained great achievements in several central nervous system disease clinical trials, which will accelerate the application of MSCs in TBI treatment.

OBJECTIVE:To explore a method of three-dimensional (3D) printing technology for preparation of personalized rat brain tissue cavity scaffolds so as to lay the foundation for the repair of traumatic brain injury (TBI) with tissue engineered customized cavity scaffolds.METHODS:Five male Sprague Dawley rats[weighing (300±10) g] were induced to TBI models by electric controlled cortical impactor. Mimics software was used to reconstruct the surface profile of the damaged cavity based on the MRI data, computer aided design to construct the internal structure. Then collagen-chitosan composite was prepared for 3D bioprinter of bionic brain cavity scaffold.RESULTS:MRI scans showed the changes of brain tissue injury in the injured side, and the position of the cavity was limited to the right side of the rat brain cortex. The 3D model of personalized cavity containing the internal structure was successfully constructed, and cavity scaffolds were prepared by 3D printing technology. The external contour of cavity scaffolds was similar to that of the injured zone in the rat TBI; the inner positive crossing structure arranged in order, and the pore connectivity was good.CONCLUSIONS:Combined with 3D reconstruction based on MRI data, the appearance of cavity scaffolds by 3D printing technology is similar to that of injured cavity of rat brain tissue, and internal positive cross structure can simulate the topological structure of the extracellular matrix, and printing materials are collagen-chitosan complexes having good biocompatibility, so it will provide a new method for customized cavity scaffolds to repair brain tissue cavity after TBI.