In the last thirty years, tissue engineering (TI) has emerged as an alternative method to regenerate tissues and organs and restore their function by implanting specific lineage cells, growth factors, or biomolecules functionalizing a matrix scaffold. Recently, several pathologies have led to bone loss or damage, such as malformations, bone resorption associated with benign or malignant tumors, periodontal disease, traumas, and others in which a discontinuity in tissue integrity is observed. Bone tissue is characterized by different stiffness, mechanical traction, and compression resistance as a function of the different compartments, which can influence susceptibility to injury or destruction. For this reason, research into repairing bone defects began several years ago to find a scaffold to improve bone regeneration. Different techniques can be used to manufacture 3D scaffolds for bone tissue regeneration based on optimizing reproducible scaffolds with a controlled hierarchical porous structure like the extracellular matrix of bone. Additionally, the scaffolds synthesized can facilitate the inclusion of bone or mesenchymal stem cells with growth factors that improve bone osteogenesis, recruiting new cells for the neighborhood to generate an optimal environment for tissue regeneration. In this review, current state-of-the-art scaffold manufacturing based on the use of polycaprolactone (PCL) as a biomaterial for bone tissue regeneration will be described by reporting relevant studies focusing on processing techniques, from traditional—i.e., freeze casting, thermally induced phase separation, gas foaming, solvent casting, and particle leaching—to more recent approaches, such as 3D additive manufacturing (i.e., 3D printing/bioprinting, electrofluid dynamics/electrospinning), as well as integrated techniques. As a function of the used technique, this work aims to offer a comprehensive overview of the benefits/limitations of PCL-based scaffolds in order to establish a relationship between scaffold composition, namely integration of other biomaterial phases’ structural properties (i.e., pore morphology and mechanical properties) and in vivo response.

The FDA’s approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the Ca_V1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic β-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas’s capability to produce insulin is still effective.

The advent of 3D printing technologies has led to a new era in tissue regeneration, offering unparalleled precision and versatility in fabricating scaffolds for various biomedical applications. Robocasting and stereolithography stand out among these technologies for their distinct advantages in engineering complex tissue structures. Robocasting, an extrusion-based 3D printing technique, has shown significant promise in cartilage tissue engineering. Its ability to precisely deposit biomaterials layer-by-layer allows the creation of porous scaffolds with encapsulated cells and bioactive molecules that improve mechanical properties and biological functionality. These scaffolds support the proliferation and differentiation of chondrocytes or mesenchymal stem cells, facilitating the regeneration of damaged cartilage. Stereolithography, a light-based 3D printing technique, offers remarkable resolution and accuracy with highly detailed structures that closely resemble the complex architecture of tissues. This makes it particularly suitable for new treatments for injuries and diseases of cartilage and ocular tissue regeneration. Integrating robocasting and stereolithography presents a synergistic approach to replicating cartilage and ocular tissues' complex physical and biological environments, offering innovative regenerative therapies. This review highlights the recent advancements and potential of robocasting and stereolithography in regenerative medicine, focusing on their applications in cartilage and ocular tissue regeneration. Graphical Abstract

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.