Functional Hydrogel Co-Remolding Migration and Differentiation Microenvironment for Severe Spinal Cord Injury Repair.

Spinal cord injury (SCI) activates nestin+ neural stem cells (NSCs), which can be regarded as potential seed cells for neuronal regeneration. However, the lesion microenvironment seriously hinders the migration of the nestin+ cells to the lesion epicenter and their differentiation into neurons to rebuild neural circuits. In this study, a photosensitive hydrogel scaffold is prepared as drug delivery carrier. Genetically engineered SDF1α and NT3 are designed and the scaffold is binary modified to reshape the lesion microenvironment. The binary modified scaffold can effectively induce the migration and neuronal differentiation of nestin+ NSCs in vitro. When implanted into a rat complete SCI model, many of the SCI-activated nestin+ cells migrate into the lesion site and give rise to neurons in short-term. Meanwhile, long-term repair results also show that implantation of the binary modified scaffold can effectively promote the maturation, functionalization and synaptic network reconstruction of neurons in the lesion site. In addition, animals treated with binary scaffold also showed better improvement in motor functions. The therapeutic strategy based on remolding the migration and neuronal differentiation lesion microenvironment provides a new insight into SCI repair by targeting activated nestin+ cells, which exhibits excellent clinical transformation prospects.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys.

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Dual-Cues Laden Scaffold Facilitates Neurovascular Regeneration and Motor Functional Recovery After Complete Spinal Cord Injury.

Complete transection spinal cord injury (SCI) severely disrupts the integrity of both neural circuits and the microvasculature system. Hence, fabricating a functional bio-scaffold that could coordinate axonal regeneration and vascular reconstruction in the lesion area may emerge as a new paradigm for complete SCI repair. In this study, a photosensitive hydrogel scaffold loaded with collagen-binding stromal cell-derived factor-1a and Taxol liposomes is capable of inducing migration of endothelial cells and promoting neurite outgrowth of neurons in vitro. In addition, when implanted into a rat T8 complete transection SCI model, the above dual-cues laden scaffold exhibits a synergistic effect on facilitating axon and vessel regeneration in the lesion area within 10 days after injury. Moreover, long-term therapeutic effects are also observed after dual-cues laden scaffold implantation, including revascularization, descending and propriospinal axonal regeneration, fibrotic scar reduction, electrophysiological recovery, and motor function improvement. In summary, the dual-cues laden scaffold has good clinical application potential for patients with severe SCI.

Binary scaffold facilitates in situ regeneration of axons and neurons for complete spinal cord injury repair.

The limited regrowth of transected axons and insufficient regeneration of lost neurons in adult mammals collectively hinder complete spinal cord injury (SCI) repair. Hence, designing an ideal bio-scaffold which could coordinate the regeneration of axons and neurons in situ might be able to effectively facilitate the reconstruction of neural circuits and the recovery of nerve function after complete SCI. In this study, a sponge-like collagen scaffold with good drug release characteristics and good nerve cell compatibility was prepared and used as a drug delivery platform. When doubly modified with Taxol liposomes and collagen-binding neurotrophic factor 3, the scaffold dually alleviated myelin-derived inhibition on neurite outgrowth of neurons and neuronal differentiation of neural stem cells in vitro. Meanwhile, the binary-drug modified scaffold was also able to simultaneously promote both axonal and neuronal regeneration when implanted into a complete transected SCI model. Additionally, the regenerated axons and neurons throughout the lesion site formed extensive synaptic connections. Finally, complete SCI rats that received binary scaffold implantation exhibited optimal neuroelectrophysiological recovery and hindlimb locomotor improvement. Taken together, implantation of the binary scaffold can establish neural bridging networks for functional recovery, representing a clinically promising strategy for complete SCI repair.

A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing.

Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients. Some studies have shown that separate administration of vascular endothelial growth factor (VEGF) or stromal cell derived factor 1α (SDF-1α) exhibited a therapeutic effect in promoting angiogenesis in the wound healing process. In this study, a collagen membrane is prepared as a drug delivery scaffold to investigate whether combined administration of SDF-1α and VEGF has a synergistic therapeutic effect on diabetic wound healing. We specifically fused a collagen-binding domain (CBD) with SDF-1α and VEGF separately, and sustained release of the two recombinant proteins from the collagen scaffold is successfully observed. Meanwhile, when a CBD-VEGF and CBD-SDF-1α co-modified scaffold is implanted in a diabetic rat skin wound model, it not only shows a synergistic effect in facilitating angiogenesis but also reduces inflammation in the short-term. Moreover, long-term results reveal that the co-modified scaffold is also able to enhance rapid wound healing, promote blood vessel regeneration, and assist cell proliferation, re-epithelialization and extracellular matrix accumulation. Taken together, our study indicates that the CBD-VEGF and CBD-SDF-1α co-modified scaffold helps in quick recovery from diabetic wounds by coordinating angiogenesis and inflammation.

On the compensation of horizontal coma aberrations in young human eyes.

The nature of the compensation of horizontal coma (Z(3)(1)) between optical elements of the human eye has been studied and the compensative mechanism has been attributed to a passive process linked to angle kappa of the eye. We measured the horizontal coma in the anterior cornea, the whole eye and the internal optics for 221 young subjects. Thirty-three eyes with minimum angle lambda and 53 eyes with relatively large angle lambda were selected from these eyes to test the hypothesis that horizontal coma compensation is linked to angle kappa. Significant horizontal coma in the anterior cornea was observed for the group with minimum angle lambda in both the right (-0.12 +/- 0.07 microm) and left eyes (0.12 +/- 0.10 microm), and this was well compensated by the internal optics so that the level of horizontal coma in the whole eye over a 6-mm pupil size was very low (-0.05 +/- 0.07 microm for OD and 0.02 +/- 0.08 microm for OS). The horizontal coma in the anterior cornea was significantly correlated to the horizontal coma in the internal optics for both the right and the left eye. The results suggest that there is another source of horizontal coma, in addition to that linked to angle kappa, in the anterior cornea, and also a new compensative mechanism to balance the corneal coma, perhaps in the posterior cornea or the lens.

[The relationship between corneal astigmatism with a vector-based method and whole eye second order wavefront aberrations].

OBJECTIVE: To investigate the relationship between corneal astigmatism and second order wavefront aberration in myopic eyes. METHODS: The corneal astigmatism and the whole eye wavefront aberrations of both eyes of 246 subjects were measured using the Humphrey corneal topography and the WASCA wavefront analyzer. According to axial of the corneal astigmatism, the subjects were divided into five groups (WR(0), WR(180), AR, OA(45) and OA(135)). The corneal astigmatism was decomposed into J(45) and J(0) with a Vector-based method, and correlated with the 2nd order Zernike aberrations (C(3) and C(5)). RESULTS: The mean corneal astigmatisms for the five groups were -1.34 D x 6.87 degrees, -1.03 D x 23.15 degrees, -0.48 D x 89.55 degrees, -0.91 D x 156.87 degrees and -1.02 D x 176.74 degrees respectively. Most of the corneal J(45) and J(0) components were correlated significantly with the C(3) and the C(5) aberrations in the whole eye. While the correlation coefficients (R(2)) between the J(45) and the C(3) were 0.138, 0.119, 0.090, 0.526 and 0.501, the R(2) between the J(0) and the C(5) were 0.711, 0.736, 0.864, 0.866 and 0.785 for the five groups respectively. CONCLUSIONS: The corneal astigmatism plays an important role in determining the 2nd order wavefront aberration in the whole eye, and the combination processes between the corneal and internal astigmatism (compensation and/or addition) change with the axial of the corneal astigmatism.