A Designer Scaffold with Immune Nanoconverters for Reverting Immunosuppression and Enhancing Immune Checkpoint Blockade Therapy

Current cancer immunotherapy based on immune checkpoint blockade (ICB) still suffers from low response rate and systemic toxicity. To overcome the limitation, a novel therapeutic platform that can revert nonimmunogenic tumors into immunogenic phenotype is highly required. Herein, a designer scaffold loaded with both immune nanoconverters encapsulated with resiquimod (iNCVs (R848)) and doxorubicin, which provides the polarization of immunosuppressive tumor‐associated macrophages (TAMs) and myeloid‐derived suppressor cells (MDSCs) into tumoricidal antigen‐presenting cells (APCs), rather than depleting them, as well as in situ vaccination that can be generated in vivo without the need to previously analyze and sequence tumor antigens to favor neoantigen‐specific T cell responses is suggested. Local and sustained release of iNCVs (R848) and doxorubicin from the designer scaffold not only reduces the frequency of immunosuppressive cells in tumors but also increases systemic antitumor immune response, while minimizing systemic toxicity. Reshaping the tumor microenivronment (TME) using the designer‐scaffold‐induced synergistic antitumor immunity with ICB effects and long‐term central and effector memory T cell responses, results in the prevention of postsurgical tumor recurrence and metastasis. The spatiotemporal modulation of TMEs through designer scaffolds is expected to be a strategy to overcome the limitations and improve the therapeutic efficacy of current immunotherapies with minimized systemic toxicity.     

Scaffolds with Tunable Properties Constituted by Electrospun Nanofibers of Polyglycolide and Poly(ε‐caprolactone)

Electrospun scaffolds constituted by different mixtures of two biodegradable polyesters are prepared. Specifically, materials with well differentiated properties can be derived from the blending of hydrophilic polyglycolide (PGA) and hydrophobic poly(ε‐caprolactone) (PCL), which are also two of the most applied polymers for biomedical uses. Electrospinning conditions are selected in order to get homogeneous and continuous fibers with diameters in the nano/micrometric range. These conditions are also applied to load the different scaffolds with curcumin (CUR) and polyhexamethylene biguanide (PHMB) as hydrophobic and hydrophilic bactericide compounds, respectively. Physicochemical characterization of both unloaded and loaded scaffolds is performed and involved Fourier transform infrared and ¹H NMR spectroscopies, morphological observations by scanning electron microscopy, study of thermal properties through calorimetry and thermogravimetric analysis, and evaluation of surface characteristics through contact angle measurements. Release behavior of the loaded scaffolds is evaluated in two different media. Results point out a well differentiated behavior where the delivery of CUR and even PHMB are highly dependent on the PGA/PCL ratio, the capability of the medium to swell the polymer matrix, and the diffusion of the selected solvent into the electrospun fibers. All samples show a bactericide effect in both hydrophilic cell culture and hydrophobic agar media.     

The Regeneration of Large-Sized and Vascularized Adipose Tissue Using a Tailored Elastic Scaffold and dECM Hydrogels

A dome-shaped elastic poly(l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue.     

聚乳酸及其共聚物制备医用多孔材料的研究进展(Ⅰ)

详细介绍了20世纪80～90年代间,聚乳酸及其共聚物制备生物可降解医用多孔支架材料技术及其发展状况,并对各种方法所制备多孔支架材料的性状进行了分析和比较.     

Specially elaborated thermally induced phase separation to fabricate poly(L‐lactic acid) scaffolds with ultra large pores and good interconnectivity

Poly(L ‐lactic acid) (PLLA) scaffolds with pore diameters from several micrometers to ～300 μm were fabricated by a specially elaborated thermally induced phase separation technique. Two different coarsening protocols, i.e., normal coarsening and multi‐step coarsening were compared in consideration of phase separation and domain growth. A normal coarsening route produced scaffolds with pore size from several micrometers to 150 μm depending on the coarsening time after phase separation, accompanying with the emergence of isolated pores at long time coarsening. Scaffolds with large pores with size up to ～300 μm were fabricated by the two‐step coarsening technique, e.g., the PLLA‐solvent (dioxane/water) system was coarsened at a temperature after phase separation for a period, followed by coarsening at a lower temperature for another period. In parallel with formation of the large pores, the interconnectivity between pores was also improved, which was evidenced by scanning electron microscopy, gelatin solution pervasion, and collagen entrapment. The present technique provides the ability to produce scaffolds with high purity, controllable microstructures, and ease of modification, and hence can be widely used in tissue engineering field. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3336–3342, 2006     

Advances in Hard Tissue Engineering Materials——Nanocellulose-based Composites

Nanocellulose (NC) has attracted much interest in the tissue engineering (TE) field because of its properties including biocompatibility, renewability, non-toxicity, functionality, and excellent mechanical performance. This review mainly focused on the advanced applications of NC-based composites in hard TE including cartilage TE, bone TE, and dental TE, illustrated the processing methods for synthesizing scaffolds including electrospinning, freeze-drying, and 3D printing, reviewed the current status of hard TE, and presented perspective on the future of TE technology.     

Carbohydrates as scaffolds in drug discovery

Drug discovery has long suffered from the difficulty of having to place pharmacophoric groups in just the right spatial arrangement to elicit the desired biological response. Although some molecule classes have been discovered that seem to be privileged structures for at least some drug-receptor interactions, there remains the challenge to design and synthesize molecules with high specific affinity to pharmacologically important targets. With their high density of stereochemical information and their relative rigidity, carbohydrates provide excellent platforms upon which to display a number of substituents in a sterically defined way, hence offering the opportunity to harness their unique features for the drug-discovery process. This review highlights the progress that has been made in the development of carbohydrate scaffolds for drug discovery.     

Osteointegration of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) scaffolds incorporated with violacein

This work reports on the production and in vivo evaluation of biodegradable scaffolds of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) incorporated with violacein, an antibiotic and antitumoral agent. PHBV produced in a bioreactor by Chromobacterium violaceum was pressed and partially sintered to produce scaffolds with 3 mm of diameter and 3 mm of height. The scaffolds were microstructurally characterized and exhibited suitable micromorphology for bone ingrowth. The PHBV-violacein scaffolds were implanted in femur of Wistar rats, extracted and analyzed after 30 and 60 days of surgery. Histological evaluation revealed that no inflammatory reaction occurred and new bone tissue was formed in the implant. The results indicated that PHBVs with violacein are potential candidates for application in regenerative bone tissue engineering.     

Solvent-Free Fabrication of Tissue Engineering Scaffolds With Immiscible Polymer Blends

A completely organic solvent-free fabrication method is developed for tissue engineering scaffolds by gas foaming of immiscible polylactic acid (PLA) and sucrose blends, followed by water leaching. PLA scaffolds with above 90% porosity and 25–200 µm pore size were fabricated. The pore size and porosity was controlled with process parameters including extrusion temperature and foaming process parameters. Dynamic mechanical analysis showed that the extrusion temperature could be used to control the scaffold strength. Both unfoamed and foamed scaffolds were used to culture glioblastoma (GBM) cells M059 K. The results showed that the cells grew better in the foamed PLA scaffolds. The method presented in the paper is versatile and can be used to fabricate tissue engineering scaffolds without any residual organic solvents.