Peripheral
nerve injury (PNI) was the leading cause of permanent dysfunction
in movement and sensation. Synthesized nerve guide conduits (NGCs)
with Schwann Cells (SCs) can help peripheral nerve regeneration. However,
poor accessibility of SCs and lack of full coverage of seeded cells
on NGCs can lead to failure of nerve regeneration across long gaps
and full functional recovery. To overcome these limitations, bone
marrow stromal cells (BMSCs) and a novel culture method were proposed
in the current study. BMSCs were harvested and seeded on a never growth
factor (NGF)-loaded PCL nanofibrous NGCs and cultured with a rotary
cell culture system (RCCS) before implantation. The NGCs were tested
in vitro with PC-12 cells to validate the bioactivity of released
NGF and to access its ability to promote neurite extension. Also,
the NGCs were tested in vivo with rat sciatic nerve model to exam
its potential in bridging the long gap (15 mm segmental defect). The
efficacy of the NGCs was investigated based on the results of the
functional test, electrophysiology test, muscle atrophy, and histological
analysis. The results of in vitro PC-12 cell study confirmed the bioactivity
of released NGF and showed a significant increase in the neurite extension
with the help of PEG-diamine and BSA. These results showed that the
novel loading method could preserve the bioactivity of growth factors
and achieve a sustained release in vitro. Besides, the results of
the in vivo study exhibited a significant increase with the combination
of all additives. These results showed that with the help of NGF and
RCCS, the NGCs with the seeded BMSCs could enhance peripheral nerve
regeneration across long nerve injury gaps.
Artificial nerve guidance conduits (NGCs) are being investigated as an alternative to autografts, since autografts are limited in supply. A polycaprolactone (PCL)-based spiral NGC with crosslinked laminin on aligned nanofibers was evaluated in vivo post a successful in vitro assessment. PC-12 cell assays confirmed that the aligned nanofibers functionalized with laminin were able to guide and enhance neurite outgrowth. In the rodent model, the data demonstrated that axons were able to regenerate across the critical nerve gap, when laminin was present. Without laminin, the spiral NGC with aligned nanofibers group resulted in a random cluster of extracellular matrix tissue following injuries. The reversed autograft group performed best, showing the most substantial improvement based on nerve histological assessment and gastrocnemius muscle measurement. Nevertheless, the recovery time was too short to obtain meaningful data for the motor functional assessments. A full motor recovery may take up to years. An interesting observation was noted in the crosslinked laminin group. Numerous new blood capillary-like structures were found around the regenerated nerve. Owing to recent studies, we hypothesized that new blood vessel formation could be one of the key factors to increase the successful rate of nerve regeneration in the current study. Overall, these findings indicated that the incorporation of laminin into polymeric nerve conduits is a promising strategy for enhancing peripheral nerve regeneration. However, the best combination of contact-guidance cues, haptotactic cues, and chemotactic cues have yet to be realized. The natural sequence of nerve regeneration should be studied more in-depth before modulating any strategies.
Osteochondral defect repair poses a significant challenge in its reconstruction as the damage is presented in both articular cartilage and the underlying subchondral bone. Thus we present a osteochondral scaffold for articular cartilage repair.
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