Zeitschrift für Gewebewissenschaft und -technik

Introduction: CXCL12 (Stromal cell-derived factor 1α, SDF - 1α) plays an important role in the nervous system development and neural repair, and is gradiently expressed in the central nervous system, mediating proper neural progenitor cell (NPCs) migration and survival. Due to a relatively short half-life and restriction of the blood-brain barrier (BBB) in systemic bioactive factor delivery, the delivery of CXCL12 and other bioactive factors has become a great challenge in research and clinical application.

Aims: In order to observe the change of concentration grade and release time of CXCL12we studied the dynamic CXCL12 prolonged release pattern with the injectable, nontoxic, modifiable and degradable RADA16-I peptide hydrogel. The hydrogel resulted in a relatively stable CXCL12 concentration and provided more suitable microenvironment for stem cell survival and migration in vitro. The following major experiments were conducted: 1. Anti-adhesion and neural protection with RADA16-I were performed in rabbit skull trauma model; 2. Fluorescent semi-quantitative CLSM was used for analysis of CXCL12 released from CXCL12 hydrogel mixture, and ELISA for detecting CXCL12 release kinetic curve was utilized; 3. Effective concentration was estimated through the peak concentration of CXCL12 load and was determined with trans-well migration assay.

Results: 1. RADA16-I alone potentially played a role in anti-adhesion and neural repair. Furthermore, RADA16-I hydrogel slow-release system smoothly released chemokine CXCL12 in vitro.

2. Stable CXCL12 released system was more effective to be used for tissue repair compared to quickly declined CXCL12 without hydrogel system.

3. The peak concentration (50 ng/ml) of CXCL12 load released from hydrogel was the functional concentration for the induction of directional migration in mouse neuronal progenitor cells (mNPCs).

Conclusions: Slow-released hydrogel system and mixture, RADA16-I and CXCL12, offered effective grade level for cell migration. This system is potentially beneficial for neural tissue protection and neural repair in clinic.

Bone tissues can repair and regenerate itself in many clinical cases, bone fractures repair without scar formation. Nevertheless, in large bone defects and pathological fractures, bone healing fail to heal. Bone grafting is defined as implantation of material which promotes fracture healing, through osteoconduction osteogenesis and osteoinduction. Ideal bone grafting depends on several factors such as defect size, ethical issues, biomechanical characteristics, tissue viability, shape and volume, associated complications, cost, graft size, graft handling, and biological characteristics. The materials that are used as bone graft can be divided into separate major categories, such as autografts, allografts, and xenografts. Synthetic substitutes and tissue-engineered biomaterials are other options. Each of these instances has some advantages and disadvantages. Between the all strategies for improving fracture healing and enhance the outcome of unification of the grafts, tissue engineering is a suitable option. A desirable tissue-engineered bone must have properties similar to those of autografts without their limitations. None of the used bone grafts has all the ideal properties including low donor morbidity, long shelf life, efficient cost, biological safety, no size restriction, and osteoconductive, osteoinductive, osteogenic, and angiogenic properties; but Tissue engineering tries to supply most of these features. In addition it is able to induce healing and reconstruction of bone defects. Combining the basis of orthopedic surgery with knowledge from different sciences like materials science, biology, chemistry, physics, and engineering can overcome the limitations of current therapies. Combining the basis of orthopedic surgery with knowledge from different sciences like materials science, biology, chemistry, physics, and engineering can overcome the limitations of current therapies.

Vascular Dementia (VaD) is a neurodegenerative disease caused by vascular lesions that leads to reduced Cerebral Blood Flow (CBF). We investigated the potential of Endothelial Progenitor-like Cells (EPC-like cells) in mitigating dementia symptoms by improving the endothelial remodelling in the ischemic VaD mice. EPC-like cells could be differentiated from CD117 positive bone marrow cells with cytokines, e.g. VEGF, b-FGF, EGF, IL-1β and IGF-1, and then characterized by surface markers (CD117+, CD31+, Tie2+ and VE-Cadherin+) and biological function of tube formation and LDL uptake. The feasibility in treating VaD was assessed by using the carotid artery ligation VaD mouse model. Among EPC-like cells, about 93% of cell population expressed CD117 molecules and 27% of cell population expressed CD31 molecules, which demonstrated the ability for the tube formation and phagocytosis. Half number of dementia mice in disease group was established with increased latency, which could be restored to normal latency with EPC-like cells treatment in another dementia mice group. In conclusion, the EPClike cells improved memory function of VaD mice, which demonstrated the potential of EPC-like cells in treating VaD.