Extracellular matrix bioink boosts stemness and facilitates transplantation of intestinal organoids as a biosafe Matrigel alternative.

Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.

Current knowledge on the multiform reconstitution of intestinal stem cell niche.

The development of "mini-guts" organoid originates from the identification of Lgr5+ intestinal stem cells (ISCs) and circumambient signalings within their specific niche at the crypt bottom. These in vitro self-renewing "mini-guts", also named enteroids or colonoids, undergo perpetual proliferation and regulated differentiation, which results in a high-performance, self-assembling and physiological organoid platform in diverse areas of intestinal research and therapy. The triumphant reconstitution of ISC niche in vitro also relies on Matrigel, a heterogeneous sarcoma extract. Despite the promising prospect of organoids research, their expanding applications are hampered by the canonical culture pattern, which reveals limitations such as inaccessible lumen, confine scale, batch to batch variation and low reproducibility. The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment. However, the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC niche. Herein, we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.

Application of a 3D-printed "fistula stent" in plugging enteroatmospheric fistula with open abdomen: A case report.

BACKGROUND: Open abdomen (OA) has been generally accepted for its magnificent superiority and effectiveness in patients with severe trauma, severe intra-abdominal infection, and abdominal compartment syndrome. In the meantime, OA calls for a mass of nursing and the subsequent enteroatomospheric fistula (EAF), which is one of the most common complications of OA therapy, remains a thorny challenge. CASE SUMMARY: Our team applied thermoplastic polyurethane as a befitting material for producing a 3D-printed "fistula stent" in the management of an EAF patient, who was initially admitted to local hospital because of abdominal pain and distension and diagnosed with bowel obstruction. After a series of operations and OA therapy, the patient developed an EAF. CONCLUSION: Application of this novel "fistula stent" resulted in a drastic reduction in the amount of lost enteric effluent and greatly accelerated rehabilitation processes.

3D-printed "fistula stent" designed for management of enterocutaneous fistula: An advanced strategy.

Enterocutaneous fistulas (ECFs) are great challenges during the open abdomen. The loss of digestive juice, water-electrolyte imbalance and malnutrition are intractable issues during management of ECF. Techniques such as "fistula patch" and vacuum-assisted closure therapy have been applied to prevent contamination of open abdominal wounds by intestinal fistula drainage. However, failures are encountered due to high-output fistula and anatomical complexity. Here, we report 3D-printed patient-personalized fistula stent for ECF treatment based on 3D reconstruction of the fistula image. Subsequent follow-up demonstrated that this stent was well-implanted and effective to reduce the volume of enteric fistula effluent.