Tissue Engineering and Regenerative Medicine

Collagen-Heparin-FGF2-VEGF Scaffolds Induce a Regenerative Gene Expression Profile in a Fetal Sheep Wound Model
Gansevoort M, Oostendorp C, Bouwman LF, Tiemessen DM, Geutjes PJ, Feitz WFJ, van Kuppevelt TH and Daamen WF
The developmental abnormality spina bifida is hallmarked by missing tissues (e.g. skin) and exposure of the spinal cord to the amniotic fluid, which can negatively impact neurological development. Surgical closure of the skin in utero limits neurological damage, but in large defects this results in scarring and contractures. Stimulating skin regeneration in utero would greatly benefit treatment outcome. Previously, we demonstrated that a porous type I collagen (COL) scaffold, functionalized with heparin (HEP), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) (COL-HEP/GF) improved pre- and postnatal skin regeneration in a fetal sheep full thickness wound model. In this study we uncover the early events associated with enhanced skin regeneration.
Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Zheng P, Liu X, Jiao Y, Mao X, Zong Z, Jia Q, Jiang HB, Lee ES and Chen Q
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
Perfusion Bioreactor Conditioning of Small-diameter Plant-based Vascular Grafts
Gorbenko N, Vaccaro JC, Fagan R, Cerro RA, Khorrami JM, Galindo L and Merna N
Vascular grafts are mainly composed of synthetic materials, but are prone to thrombosis and intimal hyperplasia at small diameters. Decellularized plant scaffolds have emerged that provide promising alternatives for tissue engineering. We previously developed robust, endothelialized small-diameter vessels from decellularized leatherleaf viburnum. This is the first study to precondition and analyze plant-based vessels under physiological fluid flow and pressure waveforms. Using decellularized leatherleaf viburnum as tissue-engineered grafts for implantation can have profound impacts on healthcare due to their biocompatibility and cost-effective production.
Macrophage Polarization: A Novel Target and Strategy for Pathological Scarring
Wang X and Liu D
Abnormal scarring imposes considerable challenges and burdens on the lives of patients and healthcare system. Macrophages at the wound site are found to be of great concern to overall wound healing. There have been many studies indicating an inextricably link between dysfunctional macrophages and fibrotic scars. Macrophages are not only related to pathogen destruction and phagocytosis of apoptotic cells, but also involved in angiogenesis, keratinization and collagen deposition. These abundant cell functions are attributed to specific heterogeneity and plasticity of macrophages, which also add an extra layer of complexity to correlational researches.
The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair
Fan L, Zhang Y, Yin X, Chen S, Wu P, Huyan T, Wang Z, Ma Q, Zhang H, Wang W, Gu C, Tie L and Zhang L
Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.
Exosomes-Shuttled lncRNA SNHG7 by Bone Marrow Mesenchymal Stem Cells Alleviates Osteoarthritis Through Targeting miR-485-5p/FSP1 Axis-Mediated Chondrocytes Ferroptosis and Inflammation
Wang Y, Hu K, Liao C, Han T, Jiang F, Gao Z and Yan J
Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown.
Determining Which Hydrostatic Pressure Regimes Promote Osteogenesis in Human Mesenchymal Stem Cells
Henstock JR, Price JCFA and El Haj AJ
Compressive loading of bone causes hydrostatic pressure changes which have been proposed as an osteogenic differentiation stimulus for mesenchymal stem cells (hMSCs). We hypothesised that hMSCs are adapted to differentiate only in response to cyclic hydrostatic pressures above critical thresholds of magnitude and frequency which correspond to physiological levels of anabolic bone loading.
Potential Use of Organoids in Regenerative Medicine
Septiana WL and Pawitan JA
In vitro cell culture is crucial for studying human diseases and development. Compared to traditional monolayer cultures, 3D culturing with organoids offers significant advantages by more accurately replicating natural tissues' structural and functional features. This advancement enhances disease modeling, drug testing, and regenerative medicine applications. Organoids, derived from stem cells, mimic tissue physiology in a more relevant manner. Despite their promise, the clinical use of regenerative medicine currently needs to be improved by reproducibility, scalability, and maturation issues.
In Vitro Assessment of Injectable Bone Marrow Aspirate Concentrates Compared to Injectable Platelet-Rich Fibrin
Fujioka-Kobayashi M, Koyanagi M, Inada R, Miyasaka A and Satomi T
Injectable platelet-rich fibrin (iPRF), a liquid form of PRF that is prepared from peripheral blood without anticoagulants, promotes tissue wound healing and regeneration. The present study focused on iPRF-like bone marrow aspirate concentrate (iBMAC) prepared without anticoagulant, and the regenerative potential of iPRF and iBMAC was compared in vitro.
A Study on iPSC-Associated Factors in the Generation of Hepatocytes
Bayarsaikhan D, Bayarsaikhan G, Kang HA, Lee SB, Han SH, Okano T, Kim K and Lee B
Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes.
Effects of Late-Passage Small Umbilical Cord-Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Lee AY, Park JY, Hwang SJ, Jang KH and Jo CH
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their anti-inflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced "small umbilical cord-derived fast proliferating cells" (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
Lipid Priming of Adipose Mesenchymal Stromal Cells with Docosahexaenoic Acid: Impact on Cell Differentiation, Senescence and the Secretome Neuroregulatory Profile
Campos J, Sampaio-Marques B, Santos D, Barata-Antunes S, Ribeiro M, Serra SC, Pinho TS, Canto-Gomes J, Marote A, Cortez M, Silva NA, Michael-Titus AT and Salgado AJ
Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential.
Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Khaswaneh RR, Abu-El-Rub E, Alzu'bi A, Almahasneh FA, Almazari RA, Ai-Jariri HF and Al-Zoubi RM
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation. Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
Efficacy of Bone Regeneration Cell Therapy Using Mesenchymal Stem Cells Originating from Embryonic Stem Cells in Animal Models; Bone Defects and Osteomyelitis
Park JH, Bae HS, Kim I, Jung J, Roh Y, Lee D, Hwang TS, Lee HC and Byun JH
Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture.
Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying Circ-Tulp4 Attenuate Diabetes Mellitus with Nonalcoholic Fatty Liver Disease by Inhibiting Cell Pyroptosis through the HNRNPC/ABHD6 Axis
Han JJ, Li J and Huang DH
Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD.
Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Han J, Sanders JGF, Andrée L, van Oirschot BAJA, Plachokova AS, van den Beucken JJJP, Leeuwenburgh SCG and Yang F
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
Enhancing Skin Regeneration Efficacy of Human Dermal Fibroblasts Using Carboxymethyl Cellulose-Coated Biodegradable Polymer
Lee YB, Lee DH, Kim YC and Bhang SH
Polylactic acid (PLA) is extensively used in the medical and cosmetic industries for skin regeneration and as a dermal filler due to its biocompatibility and biodegradability. However, the effectiveness of PLA as a cosmetic filler is limited by its slow degradation rate and poor cell attachment properties. Recent studies have focused on enhancing the performance of PLA by combining it with other materials. This study aimed to evaluate the performance of carboxymethyl cellulose (CMC), known for its high biocompatibility, in comparison with the widely used hyaluronic acid (HA).
Gingival Mesenchymal Stem Cells: A Periodontal Regenerative Substitute
Shetty SS, Sowmya S, Pradeep A and Jayakumar R
Gingival mesenchymal stem cells (GMSCs) are distinctive homogenous subset of mesenchymal stem cells (MSCs), which has its development from neural ectomesenchyme along with contributions from the perifollicular mesenchyme and the dental follicle proper. GMSCs stand apart from other dental MSCs owing to their ease of accessibility and availability with incredible long culture sustainability without any tumorigenic capability, and stable telomerase activity. Their capacity to differentiate into various cell lineages and inherent therapeutic effect in chronic inflammatory diseases like colitis, rheumatoid arthritis, systemic lupus erythematous (SLE) and diabetes makes them immensely valuable. The immunomodulatory and anti-inflammatory properties aid its usage in auto immune diseases and graft versus host disease. However, the differentiation, immunomodulatory and anti-inflammatory effects of GMSCs in periodontal tissue regeneration are less explored.
Establishment of an In Vitro Embryo-Endometrium Model Using Alginate-Embedded Mouse Embryos and Human Embryoid Body
Kim YY, Kim YJ, Kim JW, Kim J, Kim SW and Ku SY
Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers.
Rapamycin Attenuates HO-Induced Oxidative Stress-Related Senescence in Human Skin Fibroblasts
Tang Y, Yang S, Qiu Z, Guan L, Wang Y, Li G, Tu Y and Guo L
Oxidative stress plays an important role in the skin aging process. Rapamycin has been shown to have anti-aging effects, but its role in oxidative senescence of skin cells remains unclear. The aim of this study was to explore the effect of rapamycin on oxidative stress-induced skin cell senescence and to illustrate the mechanism.
Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-β and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model
Kim SH, Oh JM, Roh H, Lee KW, Lee JH and Lee WJ
Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-β/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-β-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids.