No abstract

Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p<0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.

Peripheral nerve injury is a major clinical problem and often results in a poor functional recovery. Despite obvious clinical need, treatment strategies have been largely suboptimal. In the nervous system, exosomes, which are nanosized extracellular vesicles, play a critical role in mediating intercellular communication. More specifically, microRNA carried by exosomes are involved in various key processes such as nerve and vascular regeneration, and exosomes originating from Schwann cells, macrophages, and mesenchymal stem cells can promote peripheral nerve regeneration. In this review, the current knowledge of exosomes' and their miRNA cargo's role in peripheral nerve regeneration are summarized. The possible future roles of exosomes in therapy and the potential for microRNA-containing exosomes to treat peripheral nerve injuries are also discussed.

Summary Objective To establish the performance of location specific computer measures of radiographic joint space width (JSW) compared to measurements of minimum joint space width (mJSW) for the assessment of medial compartment knee osteoarthritis (OA). The study also investigated the most disease-responsive location for measuring medial compartment JSW. Methods Serial bilateral Posterior Anterior (PA) conventional radiographs acquired with a fixed flexion protocol were obtained 36 months apart in 118 persons with knee OA participating in the Health, Aging and Body Composition (Health ABC) Study. Measurements of medial compartment mJSW and JSW at seven fixed locations were facilitated by the use of semi-automated software that delineated the femoral and tibial margins of the joint. A human reader operated custom software to verify and correct the software-drawn margins where necessary. Paired images were displayed with the reader blinded to the chronological order. The amount of joint space narrowing was measured and the standardized response mean (SRM) was used as a metric to quantify performance. Results For all subjects, the mJSW SRM value was 0.42 while, for the most responsive location specific measure of JSW, it was SRM = 0.46. For subjects with a Kellgren–Lawrence (KL) score less than or equal to 1, mJSW (SRM = 0.40) was more responsive than the new measures (Maximum SRM = 0.30). For KL = 2 or 3, SRM = 0.49 for mJSW, and SRM = 0.74 for the most responsive location specific measure of JSW. Improved responsiveness was observed in the more central portion of the joint on the more diseased knees. Conclusions Location specific computer measures of JSW are feasible and potentially provide a superior method to assess radiographic OA for more diseased subjects. This new measure has the potential to improve the power of clinical studies that use a fixed flexion protocol.