Journal of Tissue Engineering and Regenerative Medicine

In rheumatoid arthritis, dysregulated cytokine signaling has been implicated as a primary factor in chronic inflammation. Many antirheumatic and biological therapies are used to suppress joint inflammation, but despite these advances, effectiveness is not universal, and delivery is often at high doses, which can predispose patients to significant off-target effects. During chronic inflammation, the inappropriate regulation of signaling factors by macrophages accelerates progression of disease by driving an imbalance of inflammatory cytokines, making macrophages an ideal cellular target...

Myocardial infarction, stroke, and pulmonary embolism are all deadly conditions associated with excessive thrombus formation. Standard treatment for these conditions involves systemic delivery of thrombolytic agents to break up clots and restore blood flow; however, this treatment can impact the hemostatic balance in other parts of the vasculature, which can lead to excessive bleeding. To avoid this potential danger, targeted thrombolytic treatments that can successfully target thrombi and release an effective therapeutic load are necessary...

Autografting, a major treatment for bone fractures, has potential risks related to the required surgery and disease transmission. Bone morphogenetic proteins (BMPs) are the most common osteogenic factors used for bone-healing applications. However, BMP delivery can have shortcomings such as a short half-life and the high cost of manufacturing the recombinant proteins. Gene delivery methods have demonstrated promising alternative strategies for producing BMPs or other osteogenic factors using engineered cells...

Human mesenchymal stem cells/multipotent stromal cells (MSCs) hold great promise in aiding wound healing through their ability to modulate all phases of repair and regeneration, most notably their secretion of pro-regenerative paracrine factors. However, MSC clinical utility is hindered by poor survival rates post-transplantation due to the harsh microenvironment in injured tissue. Previous work has shown that the matricellular protein Tenascin-C (TNC) provides survival signaling to MSCs via the epidermal growth factor receptor by restricting its activation at the plasma membrane, resulting in enhanced prosurvival signals...

Full thickness skin loss is a debilitating problem, most commonly reconstructed using split thickness skin grafts (STSG), which do not reconstitute normal skin thickness and often result in suboptimal functional and esthetic outcomes that diminish a patient's quality of life. To address the minimal dermis present in most STSG, engineered dermal templates were developed that can induce tissue ingrowth and the formation of neodermal tissue. However, clinically available dermal templates have many shortcomings including a relatively slow rate and degree of neovascularization (∼2-4 weeks), resulting in multiple dressing changes, prolonged immobilization, and susceptibility to infection...

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown cause. The interaction of immune system cells and the secretion of inflammatory cytokines with synovial cells leads to severe inflammation in the affected joints. Currently, medications, including non-steroidal anti-inflammatory drugs, glucocorticoids, and more recently, disease-modifying anti-rheumatic drugs, are used to reduce inflammation. However, long-term use of these drugs causes adverse effects or resistance in a considerable number of RA patients...

The use of membrane barriers and bone grafting materials in endodontic surgery promotes healing by regeneration rather than repair by scar tissue. Due to its valuable regenerative and therapeutic properties, the human amniotic membrane can support ideal periapical rehabilitation and promote better healing after surgery. The current trial aimed to evaluate the amniotic membrane's healing potential and compare it with platelet-rich fibrin using color doppler sonography. The current study is a randomized, double-blinded, parallel-group, single-center study...

This review paper is motivated by a Back-to-Basics presentation given by the author at the 2022 Orthopaedic Research Society meeting in Tampa, Florida. I was tasked with providing a brief history of research leading up to the introduction of functional tissue engineering (FTE) for tendon and ligament repair. Beginning in the 1970s, this timeline focused on two common orthopedic soft tissue problems, anterior cruciate ligament ruptures in the knee and supraspinatus tendon injuries in the shoulder. Historic changes in the field over the next 5 decades revealed a transformation from a focus more on mechanics (called "bioMECHANICS") on a larger (tissue) scale to a more recent focus on biology (called "mechanoBIOLOGY") on a smaller (cellular and molecular) scale...

DNA methyltransferase inhibitor zebularine was proven to induce regeneration in the ear pinna in mice. We utilized a dorsal skin wound model to further evaluate this epigenetic inhibitor in wound healing. Full-thickness excisional wounds were made on the dorsum of 2 and 10-month-old healthy BALB/c and 3 and 8-month-old diabetic (db/db) mice, followed by topical or intraperitoneal zebularine delivery. Depending on the strain, age, dose, and delivery, the zebularine treatments either had no effect or accelerated or delayed wound closure...

The microenvironment in the healing process of large bone defects requires suitable conditions to promote osteogenesis and angiogenesis. Coaxial electrospinning is a mature method in bone tissue engineering (BTE) and allows functional modification. Appropriate modification methods can be used to improve the bioactivity of scaffolds for BTE. In this study, coaxial electrospinning with QK peptide (a Vascular endothelial growth factor mimetic peptide) and BMP-2 peptide-DFO (BD) was performed to produce double-modified PQBD scaffolds with vascularizing and osteogenic features...

Stem cell-derived islet-like clusters (ILCs) are an alternative source of pancreatic beta cells for the treatment of diabetic mellitus. An ideal 3D culture platform for the generation of ILCs of desired cluster size is a challenge due to the clustering of islet cells in the 2D culture systems. The islet cells cultured in 2D conditions produce clusters of large size, which are less efficient in terms of insulin secretion and viability. In this study, we report that ILCs formed on a PCL-based wet electrospun fibrous scaffold with larger pore size produced clusters of the desired size, compared to that cultured on a conventional electrospun sheet...

Blood vessel formation is the prerequisite for the survival and growth of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been shown to regulate angiogenesis through the secretion of exosomes containing various pro-angiogenic factors. However, whether the mineralized osteoblast-derived exosomes (MOB-Exos) containing let-7f-5p can regulate the angiogenesis of endothelial cells (ECs) is still unknown. In this study, the angiogenic capabilities of ECs respectively treated with MOB-Exos, let-7f-5p mimicked MOB-Exos (miR mimic group), and let-7f-5p inhibited MOB-Exos (miR inhibitor group) were compared through in vitro and in vivo studies...

Allotransplantation, performed using an acellular dermal matrix (ADM), plays a significant role in the cultivation of constituted and damaged organs in clinical. Herein, we fabricated an innovative ADM for allografting derived from decellularized human skin by utilizing the supercritical fluid of carbon dioxide to eliminate immunogenic components. By using histological staining, the ADM product demonstrated the successful removal of cellular constituents without exerting any harmful influence on the extracellular matrix...

Amniotic membrane (AM) has great potential as a scaffold for tissue regeneration in reconstructive surgery. To date, no systematic review of the literature has been performed for the applications of AM in wound closure of internal organs. Therefore, in this systematic review and meta-analysis, we summarize the literature on the safety and efficacy of AM for the closure of internal organs. A systematic search was performed in MEDLINE-PubMed database and OVID Embase to retrieve human and controlled animal studies on wound closure of internal organs...

With the prevalence of cardiovascular diseases, developing cardiovascular supplements is becoming increasingly urgent. The ability of cells to rapidly adhere and proliferate to achieve endothelialization is extremely important for vascular grafts. In this work, we electrospun polytetrafluoroethylene (PTFE) nanofibrous membranes and used induced crystallization to manufacture poly(ε-caprolactone) (PCL) shish-kebab microstructures on PTFE nanofibers to overcome the inertness of PTFE, and promote cell adhesion and proliferation...

Inflammasomes are intracellular structures formed upon the assembly of several proteins that have a considerable size and are very important in innate immune responses being key players in host defense. They are assembled after the perception of pathogens or danger signals. The activation of the inflammasome pathway induces the production of high levels of the pro-inflammatory cytokines Interleukin (IL)-1β and IL-18 through the caspase activation. The procedure for the implantation of a biomaterial causes tissue injury, and the injured cells will secrete danger signals recognized by the inflammasome...

Intestinal organoids and enteroids as excellent models are miniaturized and simplified for studying intestinal physiological and pathological functions, drug screening, and regenerative medicine. Recently, the application demands for organoids and enteroids in organ development and nutrition metabolism, immune and cancer research increased. But there are few comparative studies on both of them, especially in immunity and metabolism, which is also conducive to further clarifying the role of crypt stem cells and stromal cells...

Skeletal muscle tissue engineering has been a key area of focus over the years and has been of interest for developing regenerative strategies for injured or degenerative skeletal muscle tissue. Stem cells have gained increased attention as sources for developing skeletal muscle tissue for subsequent studies or potential treatments. Focus has been placed on understanding the molecular pathways that govern skeletal muscle formation in development to advance differentiation of stem cells towards skeletal muscle fates in vitro...

Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria Staphylococcus aureus, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose-dependent negative biological effect on human cells...

Efficient and large-scale expansion of mesenchymal stem/stromal cells (MSCs) has always been a formidable challenge to researchers in cell-based therapies and regenerative medicine. To reconcile major drawbacks of 2D planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on GMP-grade microcarrier for culture of umbilical cord-mesenchymal stem/stromal cells (UCMSCs), in accordance with the criteria of stem cell bank. ACISCP system is a fully closed system, which employs different models of vivaSPIN bioreactors (CytoNiche Biotech, China) for scale-up cell culture and vivaPREP (CytoNiche Biotech, China) for automated cell harvesting and cell dosage preparation...