Assembly of Interfacial Polyelectrolyte Complexation Fibers with Mineralization Gradient for Physiologically-Inspired Ligament Regeneration.

Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, interfacial polyelectrolyte complexation (IPC) spinning technique, along with a custom-designed collection system, to fabricate a hierarchical scaffold mimicking native ligament structure, is utilized. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite (HAp) mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor (CTGF) and conducting mesenchymal stem cells transplantation, the regenerative potential of the synthetic ligament is significantly amplified. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment.

Peptide-functionalized double network hydrogel with compressible shape memory effect for intervertebral disc regeneration.

As a prominent approach to treat intervertebral disc (IVD) degeneration, disc transplantation still falls short to fully reconstruct and restore the function of native IVD. Here, we introduce an IVD scaffold consists of a cellulose-alginate double network hydrogel-based annulus fibrosus (AF) and a cellulose hydrogel-based nucleus pulposus (NP). This scaffold mimics native IVD structure and controls the delivery of Growth Differentiation Factor-5 (GDF-5), which induces differentiation of endogenous mesenchymal stem cells (MSCs). In addition, this IVD scaffold has modifications on MSC homing peptide and RGD peptide which facilitate the recruitment of MSCs to injured area and enhances their cell adhesion property. The benefits of this double network hydrogel are high compressibility, shape memory effect, and mechanical strength comparable to native IVD. In vivo animal study demonstrates successful reconstruction of injured IVD including both AF and NP. These findings suggest that this double network hydrogel can serve as a promising approach to IVD regeneration with other potential biomedical applications.

Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance.

Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release.