Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell-and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well‐defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward‐lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin‐A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell‐instructive material parameter in the field of biomaterial‐guided tissue regeneration.

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Unrepaired defects in the annulus fibrosus of intervertebral discs are associated with degeneration and persistent back pain. A clinical need exists for a disc repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disc height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disc biomechanics with low herniation risk, suggesting further evaluation for disc repair may be warranted.

Reproduction of the anatomical structures and functions of tissues using cells and designed 3D scaffolds is an ongoing challenge. For this, scaffolds with appropriate biomorphic surfaces promoting cell attachment, proliferation and differentiation are needed. In this study, eight triply-periodic minimal surface (TPMS)-based scaffolds were designed using specific trigonometric equations, providing the same porosity and the same number of unit cells, while presenting different surface curvatures. The scaffolds were fabricated by stereolithography using a photocurable resin based on the biocompatible, biodegradable and rubber-like material, poly(trimethylene carbonate) (PTMC). A numerical approach was developed to calculate the surface curvature distributions of the TPMS architectures. Moreover, the scaffolds were characterized by scanning electron microscopy, micro-computed tomography and water permeability measurements. These original scaffold architectures will be helpful to decipher the biofunctional role of the surface curvature of scaffolds intended for tissue engineering applications.

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Novel 5-Z-amino-d-valerolactone (5-NHZ-VL) was synthesized with an aim to prepare degradable polyesters and copolyesters having amino pendant groups. Following a straightforward and efficient synthetic pathway, 5-NHZ-VL was obtained in only two steps and up to 50% yield. The monomer was fully characterized by 1 H NMR, 13 C NMR, ESI mass spectrometry, and HPLC. Various conventional conditions were tested for this lactone ring-opening polymerization and led to the novel corresponding poly(5-NHZ-VL) (M n ¼ 7000 g/mol; PD ¼ 1.2). Following this homopolymerization, 5-NHZ-VL was copolymerized with e-caprolactone to generate a family of copolyesters with an amino-group content ranging from 10 to 80%. Finally, the polyelectrolyte poly(5-NH 3 þ -VL) was recovered by removal of the protecting group under acidic conditions, and integrity of the polyester backbone was confirmed by 1 H NMR. V C 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 5891-5898, 2010