Improved Human Bone Marrow Mesenchymal Stem Cell Osteogenesis in 3D Bioprinted Tissue Scaffolds with Low Intensity Pulsed Ultrasound Stimulation (original) (raw)
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Advanced Biosystems, 2018
The current treatment options for bone injuries or diseases requiring surgical interventions are autografts, allografts, and artificial implantations. All suffer from significant shortcomings, e.g., insufficient donor tissue availability for autografts, risk of potential immunological rejection for allografts, and lack of proper integration with host tissues, and therefore, multiple surgeries for artificial implantation. [2,3] With increasing incidence of these disorders, alternative strategies for bone tissue repair and regeneration are desirable. Tissue engineering provides a promising tool for tissue repair and generation by growing tissues directly from cells in a bio-mimicking environment by providing a biocompatible scaffold with suitable growth factors and mechanical cues. [4] Human mesenchymal stem cells (hMSCs) have been widely investigated as a potential cell source for bone tissue engineering. [5] The advantage of the hMSCs lies in their ability to differentiate into a variety of cell types, such as osteoblasts, chondrocytes, or adipocytes when exposed to proper environmental and chemical factors. [6,7] 3D printing has emerged as a novel means for constructing a proper environment and patient injury-specific scaffolds for replacements and grafts. [7,8] The scaffolds can be printed from biodegradable materials using computer-assisted design (CAD) packages using CT or MRI images of the injury site. 3D printed structures with controllable pore sizes could also be custom designed to mimic the in vivo microenvironment, where seeded stem cells would grow, proliferate, and differentiate into desired tissues. These constructs would be implanted into the injury sites and integrated with the host tissue as the scaffold material degrades. A number of external factors such as ultrasound, [9-11] electromagnetic fields, [12] bone growth factors (bone morphogenic protein), [13] and medicines (Alendronate) [14] have been known to improve and promote bone cell growth and fracture healing. Traditionally, ultrasound has been utilized as a diagnostic modality. However, low intensity pulsed ultrasound (LIPUS)intensities less than 100 mW cm −2 and frequencies between 0.75 and 1.5 MHz-has been known to have therapeutic potentials [15] and has been approved for bone fracture healing in the United States by the Food and Drug Administration (FDA). It
Scientific reports, 2016
Lipid-coated microbubbles are used to enhance ultrasound imaging and drug delivery. Here we apply these microbubbles along with low intensity pulsed ultrasound (LIPUS) for the first time to enhance proliferation and chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in a 3D printed poly-(ethylene glycol)-diacrylate (PEG-DA) hydrogel scaffold. The hMSC proliferation increased up to 40% after 5 days of culture in the presence of 0.5% (v/v) microbubbles and LIPUS in contrast to 18% with LIPUS alone. We systematically varied the acoustic excitation parameters-excitation intensity, frequency and duty cycle-to find 30 mW/cm(2), 1.5 MHz and 20% duty cycle to be optimal for hMSC proliferation. A 3-week chondrogenic differentiation results demonstrated that combining LIPUS with microbubbles enhanced glycosaminoglycan (GAG) production by 17% (5% with LIPUS alone), and type II collagen production by 78% (44% by LIPUS alone). Therefore, integrating LIPUS and microbubbles appea...
Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update
Life
Trauma and bone loss from infections, tumors, and congenital diseases make bone repair and regeneration the greatest challenges in orthopedic, craniofacial, and plastic surgeries. The shortage of donors, intrinsic limitations, and complications in transplantation have led to more focus and interest in regenerative medicine. Structures that closely mimic bone tissue can be produced by this unique technology. The steady development of three-dimensional (3D)-printed bone tissue engineering scaffold therapy has played an important role in achieving the desired goal. Bioceramic scaffolds are widely studied and appear to be the most promising solution. In addition, 3D printing technology can simulate mechanical and biological surface properties and print with high precision complex internal and external structures to match their functional properties. Inkjet, extrusion, and light-based 3D printing are among the rapidly advancing bone bioprinting technologies. Furthermore, stem cell therap...
OBJECTIVES: Bioprinting of bone and cartilage suffers from low mechanical properties. Here we have developed a unique inkjet bioprinting approach of creating mechanically strong bone and cartilage tissue constructs using poly(ethylene glycol) dimethacrylate, gelatin methacrylate, and human MSCs. RESULTS: The printed hMSCs were evenly distributed in the polymerized PEG-GelMA scaffold during layer-by-layer assembly. The procedure showed a good biocompatibility with >80% of the cells surviving the printing process and the resulting constructs provided strong mechanical support to the embedded cells. The printed mesenchymal stem cells showed an excellent osteogenic and chondrogenic differentiation capacity. Both osteogenic and chondrogenic differentiation as determined by specific gene and protein expression analysis (RUNX2, SP7, DLX5, ALPL, Col1A1, IBSP, BGLAP, SPP1, Col10A1, MMP13, SOX9, Col2A1, ACAN) was improved by PEG-GelMA in comparison to PEG alone. These observations were consistent with the histological evaluation. CONCLUSIONS: Inkjet bioprinted-hMSCs in simultaneously photocrosslinked PEG-GelMA hydrogel scaffolds demonstrated an improvement of mechanical properties and osteogenic and chondrogenic differentiation, suggesting its promising potential for usage in bone and cartilage tissue engineering.
3D printing of bone tissue engineering scaffolds
Bioactive Materials, 2020
Tissue engineering is promising in realizing successful treatments of human body tissue loss that current methods cannot treat well or achieve satisfactory clinical outcomes. In scaffold-based bone tissue engineering, a high performance scaffold underpins the success of a bone tissue engineering strategy and a major direction in the field is to produce bone tissue engineering scaffolds with desirable shape, structural, physical, chemical and biological features for enhanced biological performance and for regenerating complex bone tissues. Three-dimensional (3D) printing can produce customized scaffolds that are highly desirable for bone tissue engineering. The enormous interest in 3D printing and 3D printed objects by the science, engineering and medical communities has led to various developments of the 3D printing technology and wide investigations of 3D printed products in many industries, including biomedical engineering, over the past decade. It is now possible to create novel bone tissue engineering scaffolds with customized shape, architecture, favorable macro-micro structure, wettability, mechanical strength and cellular responses. This article provides a concise review of recent advances in the R & D of 3D printing of bone tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of bone tissue engineering scaffolds through 3D printing.
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine, 2016
Bone tissue engineering is strongly dependent on the use of three-dimensional scaffolds that can act as templates to accommodate cells and support tissue ingrowth. Despite its wide application in tissue engineering research, polycaprolactone presents a very limited ability to induce adhesion, proliferation and osteogenic cell differentiation. To overcome some of these limitations, different calcium phosphates, such as hydroxyapatite and tricalcium phosphate, have been employed with relative success. This work investigates the influence of nano-hydroxyapatite and micro-hydroxyapatite (nHA and mHA, respectively) particles on the in vitro biomechanical performance of polycaprolactone/hydroxyapatite scaffolds. Morphological analysis performed with scanning electron microscopy allowed us to confirm the production of polycaprolactone/hydroxyapatite constructs with square interconnected pores of approximately 350 µm and to assess the distribution of hydroxyapatite particles within the poly...
Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue
Advanced healthcare materials, 2017
Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMALOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to pr...