Rapid bone regeneration within a three-dimensional defect without the use of bone grafts, exogenous growth factors, or cells remains a major challenge. We report here on the use of selfassembling peptide nanostructured gels to promote bone regeneration that have the capacity to mineralize in biomimetic fashion. The main molecular design was the use of phosphoserine residues in the sequence of a peptide amphiphile known to nucleate hydroxyapatite crystals on the surfaces of nanofibers. We tested the system in a rat femoral critical size defect by placing preassembled nanofiber gels in a 5 mm gap and analyzed bone formation with micro-computed tomography and histology. We found within 4 weeks significantly higher bone formation relative to controls lacking phosphorylated residues and comparable bone formation to that observed in animals treated with a clinically used allogenic bone matrix.

Microscale topographical features have been known to affect cell behavior. An important target in this area is to integrate top down techniques with bottom up self-assembly to create three-dimensional (3D) patterned bioactive mimics of extracellular matrices. We report a novel approach toward this goal and demonstrate its use to study the behavior of human mesenchymal stem cells (hMSCs). By incorporating polymerizable acetylene groups in the hydrophobic segment of peptide amphiphiles (PAs), we were able to micro-pattern nanofiber gels of these bioactive materials. PAs containing the cell adhesive epitope arginine-glycine-aspartic acid-serine (RGDS) were allowed to self-assemble within microfabricated molds to create networks of either randomly oriented or aligned ~30 nm diameter nanofiber bundles that were shaped into topographical patterns containing holes, posts, or channels up to 8 μm in height and down to 5 μm in lateral dimensions. When topographical patterns contained nanofibers aligned through flow prior to gelation, the majority of hMSCs aligned in the direction of the nanofibers even in the presence of hole microtextures and more than a third of them maintained this alignment when encountering perpendicular channel microtextures. Interestingly, in topographical patterns with randomly oriented nanofibers, osteoblastic differentiation was enhanced on hole microtextures compared to all other surfaces.

Tissue engineering approaches to treatment of intervertebral disc degeneration (IDD) represent a novel avenue of addressing the biologic basis of this disease. However, such approaches remain limited by their invasive nature and disruption to the annular fibrosis (AF). This study sought to explore a new minimally‐invasive tissue‐engineering approach utilizing an injection of a photopolymerizable biogel scaffold seeded with mesenchymal stem cells (MSCs) directly into the nucleus pulposus (NP). This study was performed using rabbit specimens for both in vivo and in vitro outcome measures. The treatment in this study was performed by injecting 25 μl of 10% (w/v) methacrylated gelatin biogel with 0.15% (w/v) lithium phenyl 2,4,6‐trimethylbenzoylphosphinate (LAP) and rabbit MSCs (1 × 106) cells/ml into the NP. Samples were then photopolymerized in situ using non‐ultraviolet light irradiation via a fiberoptic wire. For the in vitro arm of this study, gene expression analysis demonstrated increased anabolic activity in irradiated MSCs with and without biogel scaffolds. For the in vivo arm of this study, while GAG analysis did not demonstrate significant differences between groups, MRI analysis exhibited a trend toward improved NP matrix. Histological analysis was consistent with increased cellularity and less severe disc degeneration in the MSC + Gel group. However, osteophyte formation was noted in both Stab and MSC + Gel groups after the study period. Increased matrix gene expression of irradiated groups within in vitro studies indicates a photobiologic effect of 405 nm light. Despite promising anabolic actions, osteophyte formation and AF defects could not be avoided with implementation of this minimally‐invasive tissue‐engineering approach. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1451–1459, 2019.

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