Biodegradable Hydrophobic Injectable Polymers for Drug Delivery and Regenerative Medicine

Biodegradable, hydrophobic, and injectable liquid polymers are capable of achieving the minimally invasive, sustained, and local release of drugs. These hydrophobic injectable polymers also have potential in the area of regenerative medicine where the biomaterial should be stable for a certain period and then degrade to allow the growth of cells/tissues. This review presents exclusive coverage of biocompatible hydrophobic injectable pasty or liquid polymers that can be injected without the use of any solvent for drug delivery, tissue augmentation, and regenerative medicine application. The synthesis methodologies of several major types of hydrophobic pasty polymers used in the biomedical fields and their properties with the foremost criteria to serve as injectable biomaterial for localized drug delivery and regenerative medicine is described. The hydrophobic biodegradable injectable polymers discussed are aliphatic polyesters, polycarbonates and polyanhydrides, prepared from: lactic acid, glycolic acid, caprolactone, aliphatic diols and diacids, hydroxy fatty acids, and triglycerides such as castor oil.     

Biospecific Self‐Assembly of a Nanoparticle Coating for Targeted and Stimuli‐Responsive Drug Delivery

Biology provides a range of materials, mechanisms, and insights to meet the diverse requirements of nanomedicine. Here, a biologically based nanoparticle coating system that offers three characteristic features is reported. First, the coating can be self‐assembled through a noncovalent biospecific interaction mechanism between a lectin protein (Concanavalin A) and the polysaccharide glycogen. This biospecific self‐assembly enables the coating to be applied simply without the generation of covalent bonds. Second, glycoprotein‐based biofunctionality can be incorporated into the coating through the same noncovalent biospecific interaction mechanism. Here, the glycoprotein transferrin is incorporated into the coating since this moiety is commonly used to target cancer cells through a receptor‐mediated endocytosis mechanism. Third, the coating can be triggered to disassemble in response to a reduction in pH that is characteristic of endosomal uptake. In a proof‐of‐concept study, comparing coated and uncoated nanoparticles, model drug‐loaded nanoparticles (doxorubicin‐loaded mesoporous silica nanoparticles) are prepared and it is observed that the coated nanoparticle has enhanced cytotoxicity for cancer cell lines but attenuated cytotoxicity for noncancerous cell lines. These studies demonstrate that biology provides unique materials and mechanism appropriate to meet the needs for emerging applications in the medical and life sciences.     

Single- and Multiscale Laser Patterning of 3D Printed Biomedical Titanium Alloy: Toward an Enhanced Adhesion and Early Differentiation of Human Bone Marrow Stromal Cells

This study explores the enhancement of biocompatible titanium-based implants through surface functionalization for improved bone healing. Specifically, a near-beta type Ti-13Nb-13Zr alloy is 3D printed using laser powder bed fusion and subsequently textured using nanosecond (ns) and picosecond (ps) direct laser interference patterning (DLIP) to create single-scale and multi-scale surface textures. On these textures, the cell behavior, morphology, metabolic activity and osteogenic differentiation potential of human bone marrow stromal cells are assessed using fluorescence microscopy and MTS assays. Moreover, tissue non-specific alkaline phosphatase activity served as an early osteoblast production marker. Compared to untextured specimens, both types of textures exhibited higher metabolic activity and cell proliferation. Single-scale ns-DLIP textures encouraged cell extensions anchored in groove regions, while ps-DLIP textures with hierarchical structures promoted cell extensions attaching to nanostructures on sidewalls. The groove width and nanotopographies in groove areas facilitated cell spreading. Surface topography, roughness, and surface chemistry (surface energy, wettability) influenced cell adhesion, proliferation, and differentiation. A comprehensive evaluation of DLIP-generated surface textures, including their topography and chemical states, complements the factors affecting in vitro cell behavior. Overall, this research demonstrates the potential of surface-functionalized 3Dprinted titanium for a novel generation of biocompatible implants.     

Biodegradable Nanoparticles of Polyacrylic Acid–Stabilized Amorphous CaCO3 for Tunable pH‐Responsive Drug Delivery and Enhanced Tumor Inhibition

Inorganic nanoparticles (NPs) are promising drug delivery carriers owing to their high drug loading efficiency, scalable preparation, facile functionalization, and chemical/thermal stability. However, the clinical translation of inorganic nanocarriers is often hindered by their poor biodegradability and lack of controlled pH response. Herein, a fully degradable and pH‐responsive DOX@ACC/PAA NP (pH 7.4–5.6) is developed by encapsulating doxorubicin (DOX) in poly(acrylic acid) (PAA) stabilized amorphous calcium carbonate (ACC) NPs. The DOX‐loaded NPs have small sizes (62 ± 10 nm), good serum stability, high drug encapsulation efficiency (>80%), and loading capacity (>9%). By doping proper amounts of Sr²⁺ or Mg²⁺, the drug release of NPs can be further modulated to higher pH responsive ranges (pH 7.7–6.0), which enables drug delivery to the specific cell domains of tissues with a less acidic microenvironment. Tumor inhibition and lower drug acute toxicity are further confirmed via intracellular uptake tests and zebrafish models, and the particles also improve pharmacokinetics and drug accumulation in mouse xenograft tumors, leading to enhanced suppression of tumor growth. Owing to the excellent biocompatibility, biodegradability, and tunable drug release behavior, the present hybrid nanocarrier may find broad applications in tumor therapy.     

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

The application of combinational therapy makes up for the limitation of monotherapy and achieves superior treatment against cancer. However, the combinational therapy remains restricted by the poor tumor‐specific delivery and the abscopal effect. Herein, reactive oxygen species (ROS)‐responsive PEGylated bilirubin nanoparticles (BRNPs) are developed to encapsulate two glutathione‐activatable drugs, including dimer‐7‐ethyl‐10‐hydroxycamptothecin (d‐SN38) and dimer‐lonidamine (d‐LND). Dimerization of the drugs significantly increases the drug loading capacity and the encapsulation efficiency of nanoparticles. With the assistance of iRGD peptide (cRGDKGPDC), the cellular uptake of BRNPs is more than double when compared with the control. In response to high levels of intracellular ROS, d‐SN38 and d‐LND are rapidly released from nanoparticles (SL@BRNPs). Furthermore, the pharmacodynamic experiments verify combining SL@BRNPs with anti‐PD‐L1 antibody greatly inhibits the primary tumor of breast cancer, improves CD8+ T cells levels, and CD8+ T cells/Tregs ratios in the tumor. Additionally, it shows high immune memory effect and can prevent the growth of lung metastasis. Taken together, the strategy pioneers a new way for the rational design of nanoassemblies through the combination of activatable drug dimers and stimuli‐responsive drug release, and a successful application of novel drug delivery systems in combination with the immune checkpoint blockade antibody.