Lifeboat Foundation

In situ bioprinting, which involves 3D printing biocompatible structures and tissues directly within the body, has seen steady progress over the past few years. In a recent study, a team of researchers developed a handheld bioprinter that addresses key limitations of previous designs, i.e., the ability to print multiple materials and control the physicochemical properties of printed tissues. This device will pave the way for a wide variety of applications in regenerative medicine, drug development and testing, and custom orthotics and prosthetics.

The emergence of regenerative medicine has resulted in substantial improvements in the lives of patients worldwide through the replacement, repair, or regeneration of damaged tissues and organs. It is a promising solution to challenges such as the lack of organ donors or transplantation-associated risks. One of the major advancements in regenerative medicine is on-site (or “in situ”) bioprinting, an extension of 3D printing technology, which is used to directly synthesize tissues and organs within the human body. It shows great potential in facilitating the repair and regeneration of defective tissues and organs.

Although significant progress has been made in this field, currently used in situ bioprinting technologies are not devoid of limitations. For instance, certain devices are only compatible with specific types of bioink, while others can only create small patches of tissue at a time. Moreover, their designs are usually complex, making them unaffordable and restricting their applications.

Scientists from the NIHR Great Ormond Street Hospital Biomedical Research Centre (a collaboration between GOSH and UCL), London, and University of Padova, Italy, have shown for the first time how 3D printing can be achieved inside “mini-organs” growing in hydrogels—controlling their shape, activity, and even forcing tissue to grow into “molds.”

This can help teams study cells and organs more accurately, create realistic models of organs and disease, and even better understand how cancer spreads through different tissues.

A particularly promising area of research at the Zayed Centre for Research (a partnership between Great Ormond Street Hospital (GOSH), GOSH Charity and University College London Great Ormond Street Institute of Child Health (UCL GOS ICH)) is organoid science—the creation of micro-versions of organs like the stomach, the intestines and the lungs.

Cultured meat is gaining momentum, with large production facilities under construction and the arduous approval process for the finished products inching forward. Most of the industry’s focus thus far has been on ground beef, chicken, pork, and steak. Save for one startup that was working on lab-grown salmon, fish have been largely left out of the fray.

But last month an Israeli company called Steakholder Foods announced it had 3D printed a ready-to-cook fish fillet using cells grown in a bioreactor. The company says the fish is the first of its kind in the world, and they’re aiming to commercialize the 3D bioprinter used to create it.

Steakholder Foods didn’t produce the fish cells it used to print the fillet. They partnered with Umami Meats, a Singapore-based company working on cultured seafood. Umami created the fish cells the same way companies like Believer Meats and Good Meat create lab-grown chicken or beef: they extract cells from a fish (in a process that doesn’t harm it) and mix those cells with a cocktail of nutrients to make them divide, multiply, and mature. They signal the cells to turn into muscle and fat, which they then harvest and form into a finished product.

Will new molecular bioprinting technologies soon allow us to print our DNA?

Other research points to a future when we will be able to print DNA, nucleotide by nucleotide.

An Australian team of scientists and engineers invent a tiny, flexible, and soft robotic arm to 3D print biomaterial inside a human body.

The F3DB is a proof-of-concept 3D bioprinter that can be inserted into the body to make repairs to damaged tissue.

Researchers at the University of New South Wales, Sydney, have developed a flexible 3D bioprinter that can layer organic material directly onto organs or tissue. Unlike other bioprinting approaches, this system would only be minimally invasive, perhaps helping to avoid major surgeries or the removal of organs. It sounds like the future — at least in theory — but the research team warns it’s still five to seven years away from human testing.

The printer, dubbed F3DB, has a soft robotic arm that can assemble biomaterials with living cells onto damaged internal organs or tissues. Its snake-like flexible body would enter the body through the mouth or anus, with a pilot / surgeon guiding it toward the injured area using hand gestures. In addition, it has jets that can spray water onto the target area, and its printing nozzle can double as an electric scalpel. The team hopes its multifunctional approach could someday be an all-in-one tool (incising, cleaning and printing) for minimally invasive operations.

Continue reading “This insertable 3D printer will repair tissue damage from the inside” »

Engineers from UNSW Sydney have developed a miniature and flexible soft robotic arm which could be used to 3D print biomaterial directly onto organs inside a person’s body.

3D bioprinting is a process whereby biomedical parts are fabricated from so-called bioink to construct natural tissue-like structures.

Continue reading “3D bioprinting inside the human body could be possible thanks to new soft robot” »

Rationally designed bioinks enable bioprinting of mechanically and physiologically relevant vascular conduits.

In addition to laser-assisted bioprinting, other light-based 3D bioprinting techniques include digital light processing (DLP) and two-photon polymerization (TPP)-based 3D bioprinting. DLP uses a digital micro-mirror device to project a patterned mask of ultraviolet (UV)/visible range light onto a polymer solution, which in turn results in photopolymerization of the polymer in contact [56, 57]. DLP can achieve high resolution with rapid printing speed regardless of the layer’s complexity and area. In this method of 3D bioprinting, the dynamics of the polymerization can be regulated by modulating the power of the light source, the printing rate, and the type and concentrations of the photoinitiators used. TPP, on the other hand, utilizes a focused near-infrared femtosecond laser of wavelength 800 nm to induce polymerization of the monomer solution [56]. TPP can provide a very high resolution beyond the light diffraction limit since two-photon absorption only happens in the center region of the laser focal spot where the energy is above the threshold to trigger two-photon absorption [56].

The recent development of the integrated tissue and organ printer (ITOP) by our group allows for bioprinting of human scale tissues of any shape [45]. The ITOP facilitates bioprinting with very high precision; it has a resolution of 50 μm for cells and 2 μm for scaffolding materials. This enables recapitulation of heterocellular tissue biology and allows for fabrication of functional tissues. The ITOP is configured to deliver the bioink within a stronger water-soluble gel, Pluronic F-127, that helps the printed cells to maintain their shape during the printing process. Thereafter, the Pluronic F-127 scaffolding is simply washed away from the bioprinted tissue. To ensure adequate oxygen diffusion into the bioprinted tissue, microchannels are created with the biodegradable polymer, polycaprolactone (PCL). Stable human-scale ear cartilage, bone, and skeletal muscle structures were printed with the ITOP, which when implanted in animal models, matured into functional tissue and developed a network of blood vessels and nerves [45]. In addition to the use of materials such as Pluronic F-127 and PCL for support scaffolds, other strategies for improving structural integrity of the 3D bioprinted constructs include the use of suitable thickening agents such as hydroxyapatite particles, nanocellulose, and Xanthan and gellan gum. Further, the use of hydrogel mixtures instead of a single hydrogel is a helpful strategy. For example, the use of gelatin-methacrylamide (GelMA)/hyaluronic acid (HA) mixture instead of GelMA alone shows enhanced printability since HA improves the viscosity of mixture while crosslinking of GelMA retains post-printing structural integrity [58].

To date, several studies have investigated skin bioprinting as a novel approach to reconstruct functional skin tissue [44, 59,60,61,62,63,64,65,66,67]. Some of the advantages of fabrication of skin constructs using bioprinting compared to other conventional tissue engineering strategies are the automation and standardization for clinical application and precision in deposition of cells. Although conventional tissue engineering strategies (i.e., culturing cells on a scaffold and maturation in a bioreactor) might currently achieve similar results to bioprinting, there are still many aspects that require improvements in the production process of the skin, including the long production times to obtain large surfaces required to cover the entire burn wounds [67]. There are two different approaches to skin bioprinting: in situ bioprinting and in vitro bioprinting. Both these approaches are similar except for the site of printing and tissue maturation. In situ bioprinting involves direct printing of pre-cultured cells onto the site of injury for wound closure allowing for skin maturation at the wound site. The use of in situ bioprinting for burn wound reconstruction provides several advantages, including precise deposition of cells on the wound, elimination of the need for expensive and time-consuming in vitro differentiation, and the need for multiple surgeries [68]. In the case of in vitro bioprinting, printing is done in vitro and the bioprinted skin is allowed to mature in a bioreactor, after which it is transplanted to the wound site. Our group is working on developing approaches for in situ bioprinting [69]. An inkjet-based bioprinting system was developed to print primary human keratinocytes and fibroblasts on dorsal full-thickness (3 cm × 2.5 cm) wounds in athymic nude mice. First, fibroblasts (1.0 × 10⁵ cells/cm²) incorporated into fibrinogen/collagen hydrogels were printed on the wounds, followed by a layer of keratinocytes (1.0 × 10⁷ cells/cm²) above the fibroblast layer [69]. Complete re-epithelialization was achieved in these relatively large wounds after 8 weeks. This bioprinting system involves the use of a novel cartridge-based delivery system for deposition of cells at the site of injury. A laser scanner scans the wound and creates a map of the missing skin, and fibroblasts and keratinocytes are printed directly on to this area. These cells then form the dermis and epidermis, respectively. This was further validated in a pig wound model, wherein larger wounds (10 cm × 10 cm) were treated by printing a layer of fibroblasts followed by keratinocytes (10 million cells each) [69]. Wound healing and complete re-epithelialization were observed by 8 weeks. This pivotal work shows the potential of using in situ bioprinting approaches for wound healing and skin regeneration. Clinical studies are currently in progress with this in situ bioprinting system. In another study, amniotic fluid-derived stem cells (AFSCs) were bioprinted directly onto full-thickness dorsal skin wounds (2 cm × 2 cm) of nu/nu mice using a pressure-driven, computer-controlled bioprinting device [44]. AFSCs and bone marrow-derived mesenchymal stem cells were suspended in fibrin-collagen gel, mixed with thrombin solution (a crosslinking agent), and then printed onto the wound site. Two layers of fibrin-collagen gel and thrombin were printed on the wounds. Bioprinting enabled effective wound closure and re-epithelialization likely through a growth factor-mediated mechanism by the stem cells. These studies indicate the potential of using in situ bioprinting for treatment of large wounds and burns.