Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury.

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1ß, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.

Integration of mesenchymal stem cell sheet and bFGF-loaded fibrin gel in knitted PLGA scaffolds favorable for tendon repair.

Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA-fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF-fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction.

Local application of MDL28170-loaded PCL film improves functional recovery by preserving survival of motor neurons after traumatic spinal cord injury.

Neuronal death and organization degeneration can happen inordinately after spinal cord injury (SCI), which lead to nerve dysfunction. We aimed to determine whether local application of a cell permeable calpain I inhibitor (MDL28170) can promote SCI recovery by increasing neuronal cell viability. MDL28170-loaded polycaprolactone (PCL) film was fabricated. Scanning electron microscopy showed the surface of PCL film was smooth with holes (diameter at µM level). The PCL film was non-toxic, biological compatibility, and had good neuron adhension and slow release characteristic. MDL28170 increased VSC4.1 motor neurons' viability under tunicamycin (an endoplasmic reticulum stress) induced injury. In a traumatic SCI rat model, MDL28170-loaded PCL film reduced the area of lesion cavity, and promoted recovery of locomotor behavior. Moreover, the expression of GAP-43 was upregulated after MDL28170-loaded PCL film treatment. Thus, our findings demonstrated that localized delivery of MDL28170 could promote SCI recovery by inhibiting endoplasmic reticulum stress, preserving survival of the motor neurons, which may point out a promising therapeutic target for treating SCI patient.