Architecture of ß-lactoglobulin coating modulates bioinspired alginate dialdehyde-gelatine/polydopamine scaffolds for subchondral bone regeneration.

In this study, we developed polydopamine (PDA)-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds for subchondral bone regeneration. These polymeric scaffolds were then coated with ß-Lactoglobulin (ß-LG) at concentrations of 1 mg/ml and 2 mg/ml. Morphological analysis indicated a homogeneous coating of the ß-LG layer on the surface of network-like scaffolds. The ß-LG-coated scaffolds exhibited improved swelling capacity as a function of the ß-LG concentration. Compared to ADA-GEL/PDA scaffolds, the ß-LG-coated scaffolds demonstrated delayed degradation and enhanced biomineralization. Here, a lower concentration of ß-LG showed long-lasting stability and superior biomimetic hydroxyapatite mineralization. According to the theoretical findings, the single-state, representing the low concentration of ß-LG, exhibited a homogeneous distribution on the surface of the PDA, while the dimer-state (high concentration) displayed a high likelihood of uncontrolled interactions. ß-LG-coated ADA-GEL/PDA scaffolds with a lower concentration of ß-LG provided a biocompatible substrate that supported adhesion, proliferation, and alkaline phosphatase (ALP) secretion of sheep bone marrow mesenchymal stem cells, as well as increased expression of osteopontin (SPP1) and collagen type 1 (COL1A1) in human osteoblasts. These findings indicate the potential of protein-coated scaffolds for subchondral bone tissue regeneration. STATEMENT OF SIGNIFICANCE: This study addresses a crucial aspect of osteochondral defect repair, emphasizing the pivotal role of subchondral bone regeneration. The development of polydopamine-functionalized alginate dialdehyde-gelatine (ADA-GEL) scaffolds, coated with ß-Lactoglobulin (ß-LG), represents a novel approach to potentially enhance subchondral bone repair. ß-LG, a milk protein rich in essential amino acids and bioactive peptides, is investigated for its potential to promote subchondral bone regeneration. This research explores computationally and experimentally the influence of protein concentration on the ordered or irregular deposition, unravelling the interplay between coating structure, scaffold properties, and in-vitro performance. This work contributes to advancing ordered protein coating strategies for subchondral bone regeneration, providing a biocompatible solution with potential implications for supporting subsequent cartilage repair.

Hydrogels for Oral Tissue Engineering: Challenges and Opportunities.

Oral health is crucial to daily life, yet many people worldwide suffer from oral diseases. With the development of oral tissue engineering, there is a growing demand for dental biomaterials. Addressing oral diseases often requires a two-fold approach: fighting bacterial infections and promoting tissue growth. Hydrogels are promising tissue engineering biomaterials that show great potential for oral tissue regeneration and drug delivery. In this review, we present a classification of hydrogels commonly used in dental research, including natural and synthetic hydrogels. Furthermore, recent applications of these hydrogels in endodontic restorations, periodontal tissues, mandibular and oral soft tissue restorations, and related clinical studies are also discussed, including various antimicrobial and tissue growth promotion strategies used in the dental applications of hydrogels. While hydrogels have been increasingly studied in oral tissue engineering, there are still some challenges that need to be addressed for satisfactory clinical outcomes. This paper summarizes the current issues in the abovementioned application areas and discusses possible future developments.

Advances in Peptide-Based Hydrogel for Tissue Engineering.

The development of peptide-based materials has emerged as one of the most challenging aspects of biomaterials in recent years. It has been widely acknowledged that peptide-based materials can be used in a broad range of biomedical applications, particularly in tissue engineering. Among them, hydrogels have been attracting considerable interest in tissue engineering because they mimic tissue formation conditions by providing a three-dimensional environment and a high water content. It has been found that peptide-based hydrogels have received more attention due to mimicking proteins, particularly extracellular matrix proteins, as well as the wide variety of applications they are capable of serving. It is without a doubt that peptide-based hydrogels have become the leading biomaterials of today owing to their tunable mechanical stability, high water content, and high biocompatibility. Here, we discuss in detail various types of peptide-based materials, emphasizing peptide-based hydrogels, and then we examine in detail how hydrogels are formed, paying particular attention to the peptide structures that are incorporated into the final structure. Following that, we discuss the self-assembly and formation of hydrogels under various conditions, as well as the parameters to be considered as critical factors, which include pH, amino acid composi- tion within the sequence, and cross-linking techniques. Further, recent studies on the development of peptide-based hydrogels and their applications in tissue engineering are reviewed.

Electrosprayed Particles Loaded with Kartogenin as a Potential Osteochondral Repair Implant.

The restoration of cartilage damage is a slow and not always successful process. Kartogenin (KGN) has significant potential in this space-it is able to induce the chondrogenic differentiation of stem cells and protect articular chondrocytes. In this work, a series of poly(lactic-co-glycolic acid) (PLGA)-based particles loaded with KGN were successfully electrosprayed. In this family of materials, PLGA was blended with a hydrophilic polymer (either polyethyleneglycol (PEG) or polyvinylpyrrolidone (PVP)) to control the release rate. Spherical particles with sizes in the range of 2.4-4.1 µm were fabricated. They were found to comprise amorphous solid dispersions, with high entrapment efficiencies of >93%. The various blends of polymers had a range of release profiles. The PLGA-KGN particles displayed the slowest release rate, and blending with PVP or PEG led to faster release profiles, with most systems giving a high burst release in the first 24 h. The range of release profiles observed offers the potential to provide a precisely tailored profile via preparing physical mixtures of the materials. The formulations are highly cytocompatible with primary human osteoblasts.

On the mechanical aspect of additive manufactured polyether-ether-ketone scaffold for repair of large bone defects.

Polyether-ether-ketone (PEEK) is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing. This is due to its excellent biocompatibility, good heat and chemical stability and similar mechanical properties which mimics natural bone. In this study, three replicates of rectilinear scaffolds were designed for compression, tension, three-point bending and torsion test with unit cell size of 0.8 mm, a pore size of 0.4 mm, strut thickness of 0.4 mm and nominal porosity of 50%. Stress-strain graphs were developed from experimental and finite element analysis models. Experimental Young's modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression, 427 and 6.96 MPa respectively for tension, 257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test. The finite element model was found to be in good agreement with the experimental results. Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold, which stems from the low crystallinity of additive manufacturing PEEK. The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future, but the lower yield strength poses a design challenge.

On the Morphological Deviation in Additive Manufacturing of Porous Ti6Al4V Scaffold: A Design Consideration.

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 µm (2.5% excess) for vertical struts to 105.4 µm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 µm (4.2% excess) to 198.6 µm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 µm (-3.0% excess) for vertical struts to 92.8 µm (-8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 µm (-3.0% excess) to 168.7 µm (-21.1% excess). Compressive Young's modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young's modulus from α and ß phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.

TiO2 Nanotopography-Driven Osteoblast Adhesion through Coulomb's Force Evolution.

Nanotopography is an effective method to regulate cells' behaviors to improve Ti orthopaedic implants' in vivo performance. However, the mechanism underlying cellular matrix-nanotopography interactions that allows the modulation of cell adhesion has remained elusive. In this study, we have developed novel nanotopographic features on Ti substrates and studied human osteoblast (HOb) adhesion on nanotopographies to reveal the interactive mechanism regulating cell adhesion and spreading. Through nanoflat, nanoconvex, and nanoconcave TiO2 nanotopographies, the evolution of Coulomb's force between the extracellular matrix and nanotopographies has been estimated and comparatively analyzed, along with the assessment of cellular responses of HOb. We show that HObs exhibited greater adhesion and spreading on nanoconvex surfaces where they formed super matured focal adhesions and an ordered actin cytoskeleton. It also demonstrated that Coulomb's force on nanoconvex features exhibits a more intense and concentrated evolution than that of nanoconcave features, which may result in a high dense distribution of fibronectin. Thus, this work is meaningful for novel Ti-based orthopaedic implants' surface designs for enhancing their in vivo performance.

Fabrication of Biodegradable and Biocompatible Functional Polymers for Anti-Infection and Augmenting Wound Repair.

The problem of bacteria-induced infections threatens the lives of many patients. Meanwhile, the misuse of antibiotics has led to a significant increase in bacterial resistance. There are two main ways to alleviate the issue: one is to introduce antimicrobial agents to medical devices to get local drug releasing and alleviating systemic toxicity and resistance, and the other is to develop new antimicrobial methods to kill bacteria. New antimicrobial methods include cationic polymers, metal ions, hydrophobic structures to prevent bacterial adhesion, photothermal sterilization, new biocides, etc. Biodegradable biocompatible synthetic polymers have been widely used in the medical field. They are often used in tissue engineering scaffolds as well as wound dressings, where bacterial infections in these medical devices can be serious or even fatal. However, such materials usually do not have inherent antimicrobial properties. They can be used as carriers for drug delivery or compounded with other antimicrobial materials to achieve antimicrobial effects. This review focuses on the antimicrobial behavior, preparation methods, and biocompatibility testing of biodegradable biocompatible synthetic polymers. Degradable biocompatible natural polymers with antimicrobial properties are also briefly described. Finally, the medical applications of these polymeric materials are presented.

NPI-0052 and γ-radiation induce a synergistic apoptotic effect in medulloblastoma.

Medulloblastoma (MB) is the most common malignant solid paediatric brain tumour. The standard treatment for MB is surgical resection of the tumour, radiation and chemotherapy. This therapy is associated with high morbidity and adverse side effects. Hence, more targeted and less toxic therapies are vitally needed to improve the quality of life of survivors. NPI-0052 is a novel proteasome inhibitor that irreversibly binds the 20S proteasome subunit. This compound has anti-tumour activity in metastatic solid tumours, glioblastoma and multiple myeloma with a good safety profile. Importantly, NPI-0052 has a lipophilic structure and can penetrate the blood-brain barrier, making it a suitable treatment for brain tumours. In the present study, we performed an in silico gene expression analysis to evaluate the proteasome subunit expression in MB. To evaluate the anticancer activity of NPI-0052, we used a range of MB patient-derived MB cells and cell lines. The synergistic cell death of NPI-0052 with γ-radiation was evaluated in tumour organoids derived from patient-derived MB cells. We show that high expression of proteasome subunits is a poor prognostic factor for MB patients. Also, our preclinical work demonstrated that NPI-0052 can inhibit proteasome activity and activate apoptosis in MB cells. Moreover, we observe that NPI-0052 has a synergistic apoptotic effect with γ-radiation, a component of the current MB therapy. Here, we present compelling preclinical evidence that NPI-0052 can be used as an adjuvant treatment for p53-family-expressing MB tumours.