A Nontoxic and Biocompatible Method for Augmenting Mechanical Strength of Acellular Matrix by Silk Fibroin Impregnation.

Biological scaffolds are plagued by poor biomechanical properties and untimely degradation. These limitations have yet to be addressed without compromising their biocompatibility. It is desirable to avoid inflammation and have degradation with concomitant host collagen deposition or even site-appropriate in situ regeneration for the successful outcome of an implanted biological scaffold. This work aims to achieve this by utilizing a biocompatible method to modify acellular scaffolds by impregnating alkaline-catalyzed citric acid (CA) cross-linking between the extracellular matrix proteins and silk fibroin (SF)/SF-gelatin (SFG) blends. Combinatorial detergent decellularization was employed to prepare a decellularized porcine liver scaffold (DPL). After proving the decellularization efficiency, the scaffold underwent modification by vacuum impregnation with CA containing SF (SF100DPL) and SFG blends (SFG5050DPL and SFG3070DPL) following pre-cross-linking, drying, and post-cross-linking. The subsequent strength augmentation was demonstrated by significant improvement in tensile strength from 2.4 ± 0.4 MPa (DPL) to, 3.8 ± 0.7 MPa (SF100DPL), 3.4 ± 0.7 MPa (SFG5050DPL), and 3.5 ± 0.2 MPa (SFG3070DPL); Young's modulus from 8.7 ± 1.8 MPa (DPL) to 20 ± 1.9 MPa (SF100DPL), 13.3 ± 2.6 MPa (SFG5050DPL), and 16 ± 1.2 MPa (SFG3070DPL); and suture retention strength from 0.9 ± 0.08 MPa (DPL) to 2.3 ± 0.2 MPa (SF100DPL), 2.8 ± 1.2 MPa (SFG5050DPL), and 2.6 ± 0.9 MPa (SFG3070DPL). The degradation resistance of the modified scaffolds was also markedly improved. Being cytocompatible, its ability to incite tolerable inflammatory and immune responses was confirmed by rat subcutaneous implantation for 14, 30, and 90 days, in terms of inflammatory cell infiltration, neoangiogenesis, and in vitro cytokine release to assess B-cell and T-cell activation. Such ECM composite scaffolds with appropriate strength and biocompatibility offer great promise in soft tissue repair applications such as skin grafting.

Therapeutic delivery of nucleic acids for skin wound healing.

Though wound care has advanced, treating chronic wounds remains a challenge and there are many clinical issues that must be addressed. Gene therapy is a recent approach to treating chronic wounds that remains in its developmental stage. The limited reports available describe the therapeutic applications of various forms of nucleic acid delivery for treating chronic wounds, including DNA, mRNA, siRNA, miRNA and so on. Though these bioactive molecules represent great therapeutic potential, sustaining their bioactivity in the wound bed is a challenge. To overcome this hurdle, delivery systems are also being widely investigated. In this review, nucleic acid-based therapy and its delivery for treating chronic wounds is discussed in detail.

Thiol redox-sensitive cationic polymers for dual delivery of drug and gene.

Recently greater emphasis has been given to combination therapy for generating synergistic effects of treating cancer. Recent studies on thiol-sensitive nanocarriers for the delivery of drug or gene have shown promising results. In this review, we will examine the rationale and advantage in using nanocarriers for the combined delivery of different anticancer drugs and biologics. Here, we also discuss the role of nanocarriers, particularly redox-sensitive polymers in evading or inhibiting the efflux pump in cancer and how they modulate the sensitivity of cancer cells. The review aims to provide a good understanding of the new pattern of cancer treatment and key concerns for designing nanomedicine of synergistic combinations for cancer therapy.