Methods of Modification of Mesenchymal Stem Cells and Conditions of Their Culturing for Hyaline Cartilage Tissue Engineering

The use of mesenchymal stromal cells (MSCs) for tissue engineering of hyaline cartilage is a topical area of regenerative medicine that has already entered clinical practice. The key stage of this procedure is to create conditions for chondrogenic differentiation of MSCs, increase the synthesis of hyaline cartilage extracellular matrix proteins by these cells and activate their proliferation. The first such works consisted in the indirect modification of cells, namely, in changing the conditions in which they are located, including microfracturing of the subchondral bone and the use of 3D biodegradable scaffolds. The most effective methods for modifying the cell culture of MSCs are protein and physical, which have already been partially introduced into clinical practice. Genetic methods for modifying MSCs, despite their effectiveness, have significant limitations. Techniques have not yet been developed that allow studying the effectiveness of their application even in limited groups of patients. The use of MSC modification methods allows precise regulation of cell culture proliferation, and in combination with the use of a 3D biodegradable scaffold, it allows obtaining a hyaline-like regenerate in the damaged area. This review is devoted to the consideration and comparison of various methods used to modify the cell culture of MSCs for their use in regenerative medicine of cartilage tissue.

Biodegradable 3D Printed Scaffolds of Modified Poly(trimethylene carbonate) Composite Materials with Poly(L-lactic acid) and Hydroxyapatite for Bone Regeneration

The biodegradable scaffolds based on biomedical polymeric materials have attracted the wide interest in bone transplantation for clinical treatment to bone defects without the second operation. The composite materials of poly(trimethylene carbonate), poly(L-lactic acid) and hydroxyapatite (PTMC/PLA/HA) were prepared by the modification and blending of poly(trimethylene carbonate) (PTMC) with poly(L-lactic acid) (PLA) and hydroxyapatite nanoparticles (HA). The PTMC/PLA/HA scaffolds were further prepared by additive manufacturing using the biological 3D printing method. The PTMC/PLA/HA composite materials and scaffolds were also characterized by fourier transform infrared spectroscopy (FT-IR), GPC, automatic contact-angle, SEM, XRD, differential scanning calorimetry (DSC) and thermogravimetry (TG). Subsequently, their properties, such as the mechanic, biodegradation, drug controlled release, cell cytotoxicity, cell compatibility in vitro and proliferation/differentiation assay in vivo, were also investigated. Experiment results indicated that PTMC/PLA/HA scaffolds possessed the low toxicity, good biodegradability and good biocompatibility and then improved the cell proliferation of osteoblast cells (MC3T3-E1). Moreover, PTMC/PLA/HA enhanced the adhesion and proliferation of MC3T3-E1 cells, allowing penetration of host cells within the construct boundaries, and then can enable the growing of bone cells and induction of bone tissue regeneration. Therefore, PTMC/PLA/HA composite materials can be used as the potential biodegradable scaffolds for bone regeneration and tissue engineering in vivo.

Bio Scaffolds

Abstract‘Bio Scaffolds’ explores a series of design tectonics that emerge from a co-creation between human, machine and natural intelligences. This research establishes an integral connection between form and materiality by enabling biological materials to become a co-creator within the design and fabrication process. In this research paper, we explore a hybrid between architectural aesthetics and biological agency by choreographing natural growth through form. ‘Bio Scaffolds’ explores a series of 3D printed biodegradable scaffolds that orchestrate both Mycelia growth and degradation through form. A robotic arm is introduced into the system that can respond to the organism’s natural behavior by injecting additional Mycelium culture into a series of sacrificial frameworks. Equipped with computer vision systems, feedback controls, scanning processes and a multi-functional end-effector, the machine tends to nature by reacting to its patterns of growth, moisture, and color variation. Using this cybernetic intelligence, developed between human, machine, and Mycelium, our intention is to generate unexpected structural and morphological forms that are represented via a series of 3D printed Mycelium enclosures. ‘Bio Scaffolds’ explores an interplay between biological and computational complexity through non anthropocentric micro habitats.

Biomedical Applications of Metal 3D Printing

Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth: ( a) the improvement of mainstream additive manufacturing methods and associated feedstock; ( b) the exploration of mature, less utilized metal 3D printing techniques; ( c) the optimization of additively manufactured load-bearing structures via artificial intelligence; and ( d) the creation of monolithic, multimaterial, finely featured, multifunctional implants.

Techniques and materials used to optimize attached gingiva size: literature review

The aim of this review was to examine the techniques for performing keratinized gingival augmentation and grafts, as well as the materials used, which are often required to ensure proper wound closure. Tissue engineering of the oral mucosa represents an interesting alternative to obtain sufficient autologous tissue to repair oral soft tissue defects using biodegradable scaffolds and can improve vascularization and epithelialization, which are critical for successful outcomes.

203 Developing and Fine-Tuning Novel 3D-Printed Biodegradable Scaffolds to Promote Auricular Cartilaginous Regeneration for Surgical Implantation

Introduction Microtia, a congenital cartilaginous defect, poses major challenges in cosmetic surgery. Biodegradable polymers promote chondrogenesis, with promises of seeding cells into synthetic-polymer-implants for surgical fixation. However, existing polymers used in auricular reconstruction present limitations including inflammation, fibrosis, and extrusion. This study aimed to modulate the mechanical properties of the novel polylactic-acid/polyhydroxyalkanoate (PLA/PHA) blend by 3D-printing and hence, evaluate its suitability to the auricular microenvironment in developing next-generation reconstructs. Method Digitally defined PLA/PHA scaffolds were free-form 3D-printed at various infill densities and thicknesses. Through tensile testing, tensile moduli, yield point, maximum strength, tensile toughness, and stiffness were calculated, alongside Finite Element Analysis (FEA) and contact angle tests. Finally, preliminary cell seeding was conducted. Results Increasing infill densities of PLA/PHA scaffolds from 30%-60% significantly increased tensile moduli, yield point and maximum strength (P < 0.01). Tensile stiffness increased significantly with scaffold thicknesses between 1mm-2mm (P < 0.05). Cell studies showed promising proliferative activity. Conclusions The mechanical properties and structural stiffness of 3D-printed PLA/PHA scaffolds can be significantly tailored by altering infill density and thickness, respectively. The digitally defined interconnected pores within printed PLA/PHA scaffolds reduce stiffness mismatches between surgical-synthetic polymers and auricular cartilage, potentially promoting cell migration and nutrition transportation in future reconstructs.

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.

Antibacterial Albumin-Tannic Acid Coatings for Scaffold-Guided Breast Reconstruction

Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa, two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.