A novel titanium alloy for load-bearing biomedical implants: Evaluating the antibacterial and biocompatibility of Ti536 produced via electron beam powder bed fusion additive manufacturing process.

Additive manufacturing (AM) of Ti-based biomedical implants is a pivotal research topic because of its ability to produce implants with complicated geometries. Despite desirable mechanical properties and biocompatibility of Ti alloys, one major drawback is their lack of inherent antibacterial properties, increasing the risk of postoperative infections. Hence, this research focuses on the Ti536 (Ti5Al3V6Cu) alloy, developed through Electron Beam Powder Bed Fusion (EB-PBF), exploring bio-corrosion, antibacterial features, and cell biocompatibility. The microstructural characterization revealed grain refinement and the formation of Ti2Cu precipitates with different morphologies and sizes in the Ti matrix. Electrochemical tests showed that Cu content minimally influenced the corrosion current density, while it slightly affected the stability, defect density, and chemical composition of the passive film. According to the findings, the Ti536 alloy demonstrated enhanced antibacterial properties without compromising its cell biocompatibility and corrosion behavior, thanks to Ti2Cu precipitates. This can be attributed to both the release of Cu ions and the Ti2Cu precipitates. The current study suggests that the EB-PBF fabricated Ti536 sample is well-suited for use in load-bearing applications within the medical industry. This research also offers an alloy design roadmap for novel biomedical Ti-based alloys with superior biological performance using AM methods.

Surface modification of additive manufactured Ti6Al4V scaffolds with gelatin/alginate- IGF-1 carrier: An effective approach for healing bone defects.

The study investigates the potential of porous scaffolds with Gel/Alg-IGF-1 coatings as a viable candidate for orthopaedic implants. The scaffolds are composed of additively manufactured Ti6Al4V lattices, which were treated in an alkali solution to obtain the anatase and rutile phases. The treated surface exhibited hydrophilicity of <11.5°. A biopolymer carrier containing Insulin-like growth factor 1 was coated on the samples using immersion treatment. This study showed that the surface-modified porous Ti6Al4V scaffolds increased cell viability and proliferation, indicating potential for bone regeneration. The results demonstrate that surface modifications can enhance the osteoconduction and osteoinduction of Ti6Al4V implants, leading to improved bone regeneration and faster recovery. The porous Ti6Al4V scaffolds modified with surface coating of Gel/Alg-IGF-1 exhibited a noteworthy increase in cell viability (from 80.7 to 104.1%viability) and proliferation. These results suggest that the surface modified scaffolds have potential for use in treating bone defects.

Investigation of physical, mechanical and biological properties of polyhydroxybutyrate-chitosan/graphene oxide nanocomposite scaffolds for bone tissue engineering applications.

Mechanical properties appropriate to native tissues, as an essential component in bone tissue engineering scaffolds, plays a significant role in tissue formation. In the current study, Poly-3 hydroxybutyrate-chitosan (PC) scaffolds reinforced with graphene oxide (GO) were made by the electrospinning method. The addition of GO led to a decrease in fibers diameter, an increase in thermal capacity and an improvement in the surface hydrophilicity of nanocomposite scaffolds. A significant increase in the mechanical properties of PC/GO (PCG) nanocomposite scaffolds was achieved due to the inherent strength of GO as well as its uniform dispersion throughout the polymeric matrix owing to hydrogen bonding and polar interactions. Also, lower biological degradation of the scaffolds (~30% in 100 days) due to the presence of GO provides essential mechanical support for bone regeneration. In addition, the bioactivity results showed that GO reinforcement significantly increases the biomineralization on the surface of the scaffolds. Evaluating cell adhesion and proliferation, as well as ALP activity of MG-63 cells on PC and PCG scaffolds indicated the positive effect of GO on scaffolds' biocompatibility. Overall, the improvement of physicochemical, mechanical, and biological properties of GO-reinforced scaffolds shows the potential of PCG nanocomposite scaffolds for bone tissue engineering.

Three-Dimensional in Vitro Models: A Promising Tool To Scale-Up Breast Cancer Research.

Common models used in breast cancer studies, including two-dimensional (2D) cultures and animal models, do not precisely model all aspects of breast tumors. These models do not well simulate the cell-cell and cell-stromal interactions required for normal tumor growth in the body and lake tumor like microenvironment. Three-dimensional (3D) cell culture models are novel approaches to studying breast cancer. They do not have the restrictions of these conventional models and are able to recapitulate the structural architecture, complexity, and specific function of breast tumors and provide similar in vivo responses to therapeutic regimens. These models can be a link between former traditional 2D culture and in vivo models and are necessary for further studies in cancer. This review attempts to summarize the most common 3D in vitro models used in breast cancer studies, including scaffold-free (spheroid and organoid), scaffold-based, and chip-based models, particularly focused on the basic and translational application of these 3D models in drug screening and the tumor microenvironment in breast cancer.

Electrospun Polyurethane-Gelatin Composite: A New Tissue-Engineered Scaffold for Application in Skin Regeneration and Repair of Complex Wounds.

Wound healing is vital for patients with complex wounds including burns. While the gold standard of skin transplantation ensures a surgical treatment to heal wounds, it has its limitations, for example, insufficient donor sites for patients with large burn wounds and creation of wounds and pain when harvesting the donor skin. Therefore, tissue-engineered skin is of paramount importance. The aim of this study is to investigate and characterize an elastomeric acellular scaffold that would demonstrate the ability to promote skin regeneration. A hybrid gelatin-based electrospun scaffold is fabricated via the use of biodegradable polycarbonate polyurethane (PU). It is hypothesized that the addition of PU would enable a tailored degradation rate and an enhanced mechanical strength of electrospun gelatin. Introducing 20% PU to gelatin scaffolds (Gel80-PU20) results in a significant increase in the degradation resistance, yield strength, and elongation of these scaffolds without altering the cell viability. In vivo studies using a mouse excisional wound biopsy grafted with the scaffolds reveals that the Gel80-PU20 scaffold enables greater cell infiltration than clinically established matrices, for example, Integra (dermal regeneration matrix, DRM), a benchmark scaffold. Immunostaining shows fewer macrophages and myofibroblastic cells on the Gel80-PU20 scaffold when compared with the DRM. The findings show that electrospun Gel80-PU20 scaffolds hold potential for generating tissue substitutes and overcoming some limitations of conventional wound care matrices.

Promotion of dermal regeneration using pullulan/gelatin porous skin substitute.

Tissue-engineered dermal substitutes represent a promising approach to improve wound healing and provide more sufficient regeneration, compared with current clinical standards on care of large wounds, early excision, and grafting of autografts. However, inadequate regenerative capacity, impaired regeneration/degradation profile, and high cost of current commercial tissue-engineered dermal regeneration templates hinder their utilization, and the development of an efficient and cost-effective tissue-engineered dermal substitute remains a challenge. Inspired from our previously reported data on a pullulan/gelatin scaffold, here we present a new generation of a porous pullulan/gelatin scaffold (PG2) served as a dermal substitute with enhanced chemical and structural characteristics. PG2 shows excellent biocompatibility (viability, migration, and proliferation), assessed by in vitro incorporation of human dermal fibroblasts in comparison with the Integra® dermal regeneration template (Control). When applied on a mouse full-thickness excisional wound, PG2 shows rapid scaffold degradation, more granulation tissue, more collagen deposition, and more cellularity in comparison with Control at 20 days post surgery. The faster degradation is likely due to the enhanced recruitment of inflammatory macrophages to the scaffold from the wound bed, and that leads to earlier maturation of granulation tissue with less myofibroblastic cells. Collectively, our data reveal PG2's characteristics as an applicable dermal substitute with excellent dermal regeneration, which may attenuate scar formation.

Exosomes from acellular Wharton's jelly of the human umbilical cord promotes skin wound healing.

BACKGROUND: Compromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton's jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown. METHODS: We performed mass spectrometry on acellular gelatinous Wharton's jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo. RESULTS: Subjecting the acellular gelatinous Wharton's jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton's jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton's jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton's jelly exosomes on wound healing. CONCLUSIONS: Exosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton's jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.

Biomaterials for Skin Substitutes.

Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.

Peptide and peptide-carbon nanotube hydrogels as scaffolds for tissue & 3D tumor engineering.

The use of hybrid self-assembling peptide (EFK8)-carbon nanotube (SWNT) hydrogels for tissue engineering and in vitro 3D cancer spheroid formation is reported. These hybrid hydrogels are shown to enhance the attachment, spreading, proliferation and movement of NIH-3T3 cells relative to that observed using EFK8-only hydrogels. After five days, ∼30% more cells are counted when the hydrogel contains SWNTs. Also, 3D encapsulation of these cells when injected in hydrogels does not adversely affect their behavior. Compressive modulus measurements and microscopic examination suggest that SWNTs have this beneficial effect by providing sites for cell anchorage, spreading and movement rather than by increasing hydrogel stiffness. This shows that the cells have a particular interaction with SWNTs not shared with EFK8 nanofibers despite a similar morphology. The effect of EFK8 and EFK8-SWNT hydrogels on A549 lung cancer cell behavior is also investigated. Increasing stiffness of EFK8-only hydrogels from about 44 Pa to 104 Pa promotes a change in A549 morphology from spheroidal to a stretched one similar to migratory phenotype. EFK8-SWNT hydrogels also promote a stretched morphology, but at lower stiffness. These results are discussed in terms of the roles of both microenvironment stiffness and cell-scaffold adhesion in cancer cell invasion. Overall, this study demonstrates that applications of peptide hydrogels in vitro can be expanded by incorporating SWNTs into their structure which further provides insight into cell-biomaterial interactions. STATEMENT OF SIGNIFICANCE: For the first time we used hybrid self-assembling peptide-carbon nanotube hybrid hydrogels (that we have recently introduced briefly in the "Carbon" journal in 2014) for tissue engineering and 3D tumor engineering. We showed the potential of these hybrid hydrogels to enhance the efficiency of the peptide hydrogels for tissue engineering application in terms of cell behavior (cell attachment, spreading and migration). This opens up new rooms for the peptide hydrogels and can expand their applications. Also our system (peptide and peptide-CNT hydrogels) was used for cancer cell spheroid formation showing the effect of both tumor microenvironment stiffness and cell-scaffold adhesion on cancer cell invasion. This was only possible based on the presence of CNTs in the hydrogel while the stiffness kept constant. Finally it should be noted that these hybrid hydrogels expand applications of peptide hydrogels through enhancing their capabilities and/or adding new properties to them.