Artificial nerve conduits capable of adequately releasing neurotrophic factors are extensively studied to bridge nerve defects. However, the lack of neurotrophic factors in the proximal area and their visible effects in axonal retrograde transport following nerve injury is one of the factors causing an incomplete nerve regeneration. Herein, an advanced conduit made of silk fibroin is produced, which can incorporate growth factors and promote an effective regeneration after injury. For that, enzymatically crosslinked silk fibroin-based conduits are developed to be used as a platform for the controlled delivery of neurotrophic factors. Nerve growth factor and glial-cell line derived neurotrophic factor (GDNF) are incorporated using two different methodologies: i) crosslinking and ii) absorption method. The release profile is measured by ELISA technique. The bioactivity of the neurotrophic factors is evaluated in vitro by using primary dorsal root ganglia. When implanted in a 10 mm sciatic nerve defect in rats, GDNF-loaded silk fibroin conduits reveal retrograde neuroprotection as compared to autografts and plain silk fibroin conduit. Therefore, the novel design presents a substantial improvement of retrograde trafficking, neurons' protection, and motor nerve reinnervation.

It has been shown that hydrogel bilayered scaffolds combining cartilage-and bone-like layers are most advantageous for treating osteochondral defects. In this study, it is proposed the use of low acyl gellan gum (LAGG) for developing bilayered hydrogel scaffolds for osteochondral tissue engineering. The cartilage-like layer of the GG-based bilayered hydrogel scaffolds is composed of LAGG (2 wt%). By adding a 2 wt% LAGG aqueous solution to different amounts of HAp (5-20 wt%) it was possible to produce the bone-like layer. In vitro bioactivity tests were performed by means of soaking the LAGG/LAGG-HAp hydrogel scaffolds in a simulated body fluid solution up to 14 days. Scanning electron microscopy, Fourier transform infra-red spectroscopy and X-ray diffraction analyses demonstrated that apatite formation is limited to the bone-like layer of the LAGG/LAGG-HAp bilayered hydrogel scaffolds.

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Natural‐based hydrogels have been widely used for tissue engineering and regenerative medicine (TERM) as a platform to better mimic the native extracellular matrix of different tissues. Polysaccharides and proteins of natural origin have been functionalized, tuned, and processed used different methods to produce different scaffolds and medical devices. Herein, the recent reports dealing with the application of natural‐based hydrogels in TERM strategies are overviewed. Moreover, different methodologies used to process the polymeric hydrogels are also described as well as the most relevant strategies used within the scope of TERM.

Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers are limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(ɛ-lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of 16 aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically crosslinked methacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels, and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in the proximity of the implanted gel surface. Copyright © 2016 John Wiley & Sons, Ltd.

A silk fibroin bioink for the production of patient‐specific memory‐shape implants is proposed by Joaquim M. Oliveira and co‐workers in article number https://doi.org/10.1002/adhm.201701021 using a fast setting enzymatic‐based cross‐linking reaction. The reproducibility and the reliability of this bioink allow the production of different scaffolds with superior mechanical performance. Its versatility gives new opportunity concerning tissue engineering approaches, in particular for the biofabrication of patient‐specific memory‐shape implants.

The incorporation and delivery of neurotrophic factors that stimulate nerve repair in previously developed tunable enzymatically crosslinked silk fibroin‐based conduits are presented. In article number 2000753 by Joaquim M. Oliveira and co‐workers, glial cell line‐derived neurotrophic factor (GDNF), acting upon motor and sensory neurons, also instigating angiogenesis, uses these conduits as a platform for its controlled delivery, enhancing motor and sensory regeneration both in vivo and in vitro.

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