Biomaterials
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SHH plays a significant role in peripheral nerve regeneration and has clinical potential to be used as a regenerative therapy for the CN in prostatectomy patients and in other patients with neuropathy of peripheral nerves. Efforts to regenerate the cavernous nerve (CN), which provides innervation to the penis, have been minimally successful, with little translation into improved clinical outcomes. ⋯ Morphological, functional and molecular analysis revealed that SHH protein is essential to maintain CN architecture, and that SHH treatment promoted CN regeneration, suppressed penile apoptosis and caused a 58% improvement in erectile function in less than half the time reported in the literature. These studies show that SHH has substantial clinical application to regenerate the CN in prostatectomy and diabetic patients, that this methodology has broad application to regenerate any peripheral nerve that SHH is necessary for maintenance of its structure, and that this nanotechnology method of protein delivery may have wide spread application as an in vivo delivery tool in many organs.
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Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. ⋯ Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.
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Spinal cord crushed injury is clinically common. Promoting targeted neural regeneration at the crushed site of spinal cord could be important for the repair. It has been demonstrated in our previous work that native human BDNF fused with a collagen-binding domain (CBD-BDNF) can bind to collagen specifically to exert the neurotrophic effect on promoting axonal regeneration. ⋯ We thus speculate that CBD-BDNF will bind to the extracellular matrix collagen and concentrate at the injury site to improve the therapy. Using the rat spinal cord crushed injury model, we have found that CBD-BDNF by one-time intrathecally injection could be retained and concentrated at the injury site for a longer time than native BDNF without collagen-binding domain. CBD-BDNF could promote better neural regeneration and locomotion recovery.
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Efficacious hemostatic agents have significant potential for use in rapid exsanguinating hemorrhage control by emergency medical technician or military medic nowadays. Unfortunately, the topical hemostats currently available in market still have various disadvantages. In this study, a series of macroporous chitosan coated mesoporous silica xerogel beads (CSSX) with good biocompatibility were developed. ⋯ The textural properties of the CSSX beads were optimized by in vitro and in vivo evaluation for promoting blood clotting and the results indicated that the prepared CSSX beads can significantly accelerate the contact activation pathway of coagulation cascade and produce desirable hemostasis, with the best efficiency from the CSSX prepared with 2% chitosan and 5% PEG. Furthermore, these CSSX beads were observed to create no exothermic reaction and the subsequential tissue thermal injury by histological examination, and exhibited no obvious cytotoxicity even after 7 days. The results of the present study forward CSSX bead as a safe hemostatic system and present a platform for further optimization studies of materials with enhanced hemostatic capabilities for specific injury types.
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Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4h/day for 30 days. ⋯ Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2+/-35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2+/-38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue.