ADSC-derived exosomes-coupled decellularized matrix for endometrial regeneration and fertility restoration.

Endometrium is suspectable to severe injury due to recurrent abortion, curettage or intrauterine infection which could lead to pathological conditions and sabotage women's fertility. Promoting endometrium regeneration is the core of the treatments to uterine related infertility. Patients who received traditional treatments can only expect limited effects, thereby novel therapies are badly in need to promote endometrium regeneration. Here we generated a decellularized extracellular matrix (ECM) from porcine dermis, and composited adipose stem cell derived exosomes (ADSC-exos) on it (ECM@ADSC-exos). In vitro experiments proved that ECM@ADSC-exos exhibited good cytocompatibility and could improve cell proliferation, migration and angiogenesis. We also observed that, when implanted in the uterine cavity of a rat model of endometrium injury, ECM@ADSC-exos improved endometrium regeneration, enhanced local angiogenesis, promoted myometrium repair and finally preserved fertility. Our results proved that ECM@ADSC-exos could be a novel option for endometrium regeneration.

Integrity of the ECM Influences the Bone Regenerative Property of ECM/Dicalcium Phosphate Composite Scaffolds.

Due to the limitation of clinical autologous bone supply and other issues, the development of bone regeneration materials is still a hot topic. Natural tissue-derived bone repair materials have good biocompatibility and degradability, but their structure and properties are likely to be adversely affected during terminal sterilization. In this study, a composite scaffold consisting of the acellular extracellular matrix and dicalcium phosphate (ECM/DCP) was fabricated and terminally sterilized by γ-ray irradiation. In addition, the ECM/DCP scaffold was saturated with water and was also sterilized by γ-ray irradiation (RX-ECM/DCP). Results showed that the triple helix structure of collagen was better maintained in RX-ECM/DCP than in ECM/DCP. The thermal stability of RX-DCP/ECM was much better than that of ECP/ECM. The in vitro and in vivo performances of both types of scaffolds were also evaluated. The RX-ECM/DCP scaffold exhibited better in vitro bioactivity than that of the ECM/DCP scaffold as evidenced by more mineral formation in the simulated body fluid. In addition, RX-ECM/DCP also induced more effective bone regeneration than the ECM/DCP scaffold did in a rat calvarial defect model. Results sufficiently demonstrated that the addition of water to the scaffold could protect the structure of the ECM/DCP scaffold from being damaged by γ-ray irradiation during the terminal sterilization process. In summary, this study demonstrated a means to protect the ECM structure, which in turn led to the improvement of bone regenerative properties of the materials during γ-ray irradiation of ECM-based bone repair materials.

Transformation of acellular dermis matrix with dicalcium phosphate into 3D porous scaffold for bone regeneration.

Animal derived biomaterials have attracted much attentions in treating large size bone defect due to their excellent biocompatibility and potent bioactivities offered by the biomacromolecules and growth factors contained in these materials. Dermis-derived matrix (ADM) has been used as skin grafts and wound dressings for decades, however its application in bone tissue engineering has been largely limited as ADM possesses a dense structure which does not support bone tissue ingrowth. Recently, we have successfully fabricated porous scaffold structure using an ADM with the aid of micronization technique. When integrated with inorganic components such as calcium phosphate, ADM could be transformed to bone graft substitutes with desirable osteogenic properties. While purified and chemically cross-linked collagen has lost its natural structure, our ADM successfully preserved natural tropocollagen structure, as well as other bioactive components. A composite scaffold was fabricated by incorporating dicalcium phosphate (DCP) microparticles into ADM microfibers and freeze-dried to form a highly porous structure. Unlike conventional ADM materials, this scaffold possesses high porosity with interconnected pores. More importantly, our evaluation data demonstrated that it performed much more effective in treating critical bone defects in comparison with best commercial product on the market. In a head-to-head comparison with a commercial bone graft material Bongold®, the ADM/DCP scaffold showed superior osteogenic capacity by filling the defect with well-organized new bone tissue in a rabbit radius segmental defect model. Put together, our results exhibited a novel bone graft substitute was developed by circumventing processing barriers associated with natural ADM, which offers another novel bone graft substitute for bone regeneration.

Utility of Air Bladder-Derived Nanostructured ECM for Tissue Regeneration.

Exploration for ideal bone regeneration materials still remains a hot research topic due to the unmet clinical challenge of large bone defect healing. Bone grafting materials have gradually evolved from single component to multiple-component composite, but their functions during bone healing still only regulate one or two biological processes. Therefore, there is an urgent need to develop novel materials with more complex composition, which convey multiple biological functions during bone regeneration. Here, we report an naturally nanostructured ECM based composite scaffold derived from fish air bladder and combined with dicalcium phosphate (DCP) microparticles to form a new type of bone grafting material. The DCP/acellular tissue matrix (DCP/ATM) scaffold demonstrated porous structure with porosity over 65% and great capability of absorbing water and other biologics. In vitro cell culture study showed that DCP/ATM scaffold could better support osteoblast proliferation and differentiation in comparison with DCP/ADC made from acid extracted fish collagen. Moreover, DCP/ATM also demonstrated more potent bone regenerative properties in a rat calvarial defect model, indicating incorporation of ECM based matrix in the scaffolds could better support bone formation. Taken together, this study demonstrates a new avenue toward the development of new type of bone regeneration biomaterial utilizing ECM as its key components.