Porous tantalum-composited gelatin nanoparticles hydrogel integrated with mesenchymal stem cell-derived endothelial cells to construct vascularized tissue in vivo

The ideal scaffold material of angiogenesis should have mechanical strength and provide appropriate physiological microporous structures to mimic the extracellular matrix environment.In this study,we constructed an integrated three-dimensional scaffold material using porous tantalum(pTa),gelatin nanoparticles(GNPs)hydrogel,and seeded with bone marrow mesenchymal stem cells(BMSCs)-derived endothelial cells(ECs)for vascular tissue engineering.The characteristics and biocompatibility of pTa and GNPs hydrogel were evaluated by mechanical testing,scanning electron microscopy,cell counting kit,and live-cell assay.The BMSCs-derived ECs were identified by flow cytometry and angiogenesis assay.BMSCs-derived ECs were seeded on the pTa-GNPs hydrogel scaffold and implanted subcutaneously in nude mice.Four weeks after the operation,the scaffold material was evaluated by histomorphology.The superior biocompatible ability of pTa-GNPs hydrogel scaffold was observed.Our in vivo results suggested that 28 days after implantation,the formation of the stable capillary-like network in scaffold material could be promoted significantly.The novel,integrated pTa-GNPs hydrogel scaffold is biocompatible with the host,and exhibits biomechanical and angiogenic properties.Moreover,combined with BMSCs-derived ECs,it could construct vascular engineered tissue in vivo.This study may provide a basis for applying pTa in bone regeneration and autologous BMSCs in tissue-engineered vascular grafts.

Engineering biomolecular systems: Controlling the self-assembly of gelatin to form ultra-small bioactive nanomaterials

The size of nanocarriers determines the biological property of the materials, especially as it relates to intratumoral distribution. Previous research has shown that sizes of 10-50 nm penetrate deep inside the tumor, resulting in better efficacy. On the other hand, studies have shown that gelatin exhibits excellent biological properties, including compatibility, degradability, and toxicity. Therefore, FDA approved gelatin as a safe material to use as an excipient in injectables. The bottleneck is the nonexistence of smaller-sized gelatin nanoparticles (GNPs) to realize the full potential of these biomaterials. Yet, GNPs with sizes of less than 50 nm have not been reported;the synthetic strategy reported in the literature uses “uncontrolled crosslinking coupled with nanoprecipitation”, resulting in larger particle size. We have developed a new method to self-assemble gelatin strands by using an anionic, phosphate-based crosslinker and controlled precipitation. The method we developed produced ultra-small gelatin nanoparticles (GX) of size 10 nm with a high degree of reproducibility, and it was characterized using dynamic light scattering (DLS), Energy-dispersive X-ray spectroscopy (EDS), High-resolution transmission, and scanning electron microscopy (HR-TEM/STEM). We also explored GX as a bioactive platform to encapsulate imaging and therapy agents within the cavity. Interestingly, we were able to encapsulate 2 nm size gold nanoparticles within the void of GX. The versatile nature of the GX particles was further demonstrated by surface functionalizing with larger size gelatin nanoparticles to form core-satellite nanocomposites. Additionally, we studied the tumor penetrability of dye-tagged 10, 50, and 200 nm gelatin nanoparticles. The study showed that smaller size gelatin nanoparticles penetrate deeper tumor regions than larger particles. In general, GX was efficient in penetrating the inner region of the spheroids. The results demonstrate the potential capabilities of ultra-small GX nanoparticles for multi-staged payload delivery, diagnostics, and cancer therapy.