Tissue engineering and regenerative medicine最新文献

Background: Tissue-engineered pulmonary valves (TEPVs) hold considerable potential for improving outcomes in valve replacement surgeries. We investigated the surgical outcomes of TEPVs replacement in sheep, specifically examining the effects of valve type (decellularized versus adipose-derived stem cell-seeded valve [ADSC]) and the animal's age at the surgery. The primary goals were to assess survival rates, postoperative complications, and the effects of cardiopulmonary bypass (CPB) on homeostasis.

Methods: Nineteen juvenile and adult sheep were randomly assigned to orthotopic pulmonary valve replacement using either decellularized (DECELL, n = 10) or ADSC-seeded valves (CELL, n = 9). Blood gas analysis was conducted intraoperatively and postoperatively to assess CPB-related metabolic changes. The follow-up period after surgery was 6 months. Key demographic and operative parameters were recorded, and early and late postoperative complications were monitored.

Results: No significant differences were observed in operative parameters or postoperative complications between the DECELL and CELL groups. Adult sheep exhibited longer anesthesia, CPB, and operative times due to tissue fragility but demonstrated better long-term survival than juveniles, who experienced more late-stage complications, including endocarditis. CPB exposure increased lactate and reduced hemoglobin levels, particularly in adult sheep, affecting homeostasis. The overall mortality rate was 42.1%, with deaths primarily attributed to congestive heart failure and endocarditis.

Conclusion: Valve type did not significantly affect short-term outcomes and ADSC-seeding had no significant impact on operative parameters, postoperative complications, or survival rate. However, age remained a crucial factor influencing both surgical complexity and survival, highlighting the need for age-specific strategies in tissue-engineered valve applications.

Background: Adipose-derived stem cells (ADSCs) promote lymphangiogenesis, though their integration with vascularized lymph node transfer (VLNT) is not well-explored. Unlike ADSCs, the stromal vascular fraction (SVF) can be obtained intraoperatively without the need for cell culture, making it ideal for incorporation into VLNT in a single-stage surgical procedure. This study evaluates the impacts of combined VLNT and SVF therapy using a rabbit hindlimb model.

Method: New Zealand white rabbits were divided into four groups: control, VLNT only, SVF only, and combined VLNT plus SVF. The VLNT procedure involved transferring a pedicled lymph node flap, while the SVF was harvested and injected into the perinodal tissue. Postoperative assessments included measuring edema volume, performing ICG lymphography, conducting histological analysis, and measuring VEGF-C and LYVE-1 expression.

Results: Initial increases in hindlimb edema volume were noted, but a significant decrease occurred by week 4, particularly in the VLNT group and VLNT plus SVF group compared to the control group. Histological evaluations indicated that the combined treatment group preserved superior structural integrity of the lymph nodes, with a decreased proportion of fibroadipose tissue compared to the VLNT-only group. Elevated VEGF-C expression was observed in the SVF-treated groups, as confirmed by both RT-PCR and ELISA analyses at week 4. Additionally, the combined VLNT plus SVF group showed increased LYVE-1 expression by week 8.

Conclusion: The results suggest that SVF can be effectively integrated with VLNT in a single-stage procedure, enhancing the viability and structural integrity of vascularized lymph nodes. These results highlight the potential of this combined approach as a promising therapeutic strategy for advanced-stage lymphedema, meriting further exploration in clinical trials.

Background: Bone scaffolds are artificial structures used for restoring bone functionality via the reconstruction and repair of bone tissue. Although these scaffolds interact seamlessly with the surrounding tissue, conventional scaffold designs often fail to consider the microstructure of the surrounding bone, leading to reduced mechanical performance. This study proposed an implantation angle optimization approach for bone scaffolds that considers the microstructures around the implant, thus improving the mechanical properties of commonly used scaffolds.

Method: This study proposed a novel method for optimizing the implantation angle of bone scaffolds, thereby enhancing their mechanical performance and integration with the surrounding bone tissue. A finite element model based on the imaging data of the bone scaffold within the skeletal system was constructed. Then, the structural behavior under external load was analyzed to determine the optimal implantation angle by rotating the bone scaffold.

Result: Bone scaffolds with optimized angles show up to 7.53% strain energy difference between the scaffold and native bone, which improves load transfer and supports more natural bone remodeling. These results suggest that this approach enhances scaffold stability and reduces the risk of implant failure.

Conclusion: The results highlight the potential of the proposed approach to optimize the implantation angle considering the bone microstructure, thus significantly enhancing scaffold performance. The combination of these strategies shows significant potential for advancing bone-repair solutions and improving patient outcomes in orthopedic surgeries.

Background: The design of bone biomaterials has shifted from promoting bone differentiation to "immune osteogenic coupling". Macrophages play a key role in immune regulation, with their polarization state critically shaping the bone tissue immune microenvironment. While collagen membranes, as classic guided bone regeneration (GBR) barriers, offer excellent biocompatibility and degradability, they lack inherent bone induction and immune regulation capabilities, limiting their use in complex bone defect repair.

Methods: In this study, we proposed a novel optimization strategy utilizing phase-transited lysozymes (PTL) incorporating strontium (Sr²⁺) into marine collagen membranes (Sr-PTL-MCM) and investigate their osteoimmunomodulatory effect through a series of experiments.

Results: Sr-PTL-MCM were successfully synthesized via the PTL technique and continuously released Sr²⁺ ions over 7 days. Sr-PTL-MCM can effectively induce macrophage polarization from the M0 to M2 phenotype, suppresses the secretion of inflammatory cytokines, thereby enhancing mBMSCs osteogenic differentiation. RNA-sequence analysis reveals that Sr-PTL-MCM promotes M2 polarization via JAK-STAT and MAPK signaling pathways. In vivo experiments confirm its ability to create a favorable bone immune microenvironment, promoting bone growth and regeneration.

Conclusion: In conclusion, incorporating Sr ions into collagen via PTL technique represents a promising approach for developing collagen membranes with immunomodulatory characteristics, thereby providing a novel and effective strategy for bone defect repair.

Background: Enamel regeneration and remineralization are critical for restoring enamel integrity, as natural enamel lacks the ability to regenerate due to the absence of ameloblasts. The increasing prevalence of dental caries and the irreversible nature of enamel damage highlight the need for advanced repair strategies.

Methods: This review examines the latest advancements in enamel regeneration and remineralization, focusing on biomaterials, nanotechnology-based approaches, and bioengineering strategies. Google Scholar, Scopus (Elsevier), and PubMed databases were used for the selection of literature. The search included key terms such as "enamel regeneration," "biomimetic enamel repair," "stem cell-based enamel regeneration," "nanotechnology in enamel repair," "hydroxyapatite enamel remineralization," and "biomaterials for enamel remineralization."

Results: Various strategies have been explored for enamel remineralization, including self-assembling peptides, dendrimers, hydrogels, and electrospun mats, each demonstrating varying success in laboratory and preclinical studies. While casein-phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) combined with fluoride remains a widely used clinical remineralization agent, integrating CPP-ACP with nanotechnology is an emerging area requiring further research. Enamel bioengineering approaches utilizing stem/progenitor cells offer potential, though challenges remain in achieving clinical translation.

Conclusion: Despite advancements, replicating the hierarchical structure and mechanical properties of natural enamel remains challenging. Nanotechnology-driven approaches, bioengineered scaffolds, and interdisciplinary collaboration hold promise for optimizing enamel regeneration techniques. Further research is necessary to enhance clinical applicability and develop scalable, effective treatments for enamel restoration.

Background: The ultimate goal of regenerative medicine is to restore damaged tissues to a healthy state in the body. Direct reprogramming, also referred to as transdifferentiation, holds significant therapeutic potential by converting abundant somatic cells, such as fibroblasts, into functionally distinct cell types for tissue regeneration. Despite its potential applications in regenerative medicine, direct reprogramming faces major challenges, including low efficiency and poor In vivo applicability. In this study, we propose a novel therapeutic strategy for osteoporosis based on In vivo direct reprogramming using a stepwise delivery approach that first enhances cellular stemness and subsequently induces osteogenic transdifferentiation. Enhancing stemness in lineage-committed cells facilitates their conversion into other functional cell types.

Method: To investigate the efficiency of direct reprogramming via stepwise delivery, we utilized valproic acid (VPA) and tauroursodeoxycholic acid (TUDCA) as reprogramming and bone-stimulating factors, respectively. VPA increased the expression of stemness genes, including Oct4, Nanog, and Sox2, and subsequent treatment of TUDCA enhanced the expression of osteogenic genes in the mouse fibroblast. Targeted delivery of these factors to fibroblasts surrounding bone tissue, enabling subsequent direct reprogramming into osteoblasts, was achieved using bisphosphonate (BP)-conjugated lipid nanoparticles as carriers.

Results: Our findings demonstrate that sequential induction of cell reprogramming and tissue regeneration through stepwise administration of VPA and TUDCA significantly enhances therapeutic efficacy in a mouse model of osteoporosis compared to their simultaneous administration.

Conclusion: This stepwise bone-targeted drug delivery system presents a promising strategy for osteoporosis treatment via In vivo direct reprogramming.

Background: Wound healing remains a significant challenge in healthcare, particularly for complex and chronic wounds where conventional treatments often fail to provide effective solutions. Recent advances in nanofiber technology have opened new avenues for wound management by offering biomimetic structures that support tissue regeneration. Due to their high surface area-to-volume ratio and porosity, nanofibers closely resemble the extracellular matrix, facilitating an optimal environment for cell adhesion, proliferation, and differentiation.

Methods: This review examines the role of nanofiber-based wound dressings, highlighting their unique advantages in drug delivery, moisture retention, and antimicrobial protection. Additionally, emerging trends such as smart wound dressings responsive to environmental stimuli and multifunctional nanofiber systems are discussed.

Results and conclusion: Nanofiber technology has demonstrated significant potential in enhancing wound healing outcomes by providing an advanced platform for therapeutic delivery and tissue regeneration. Furthermore, the integration of nanofibers with artificial intelligence and biotechnology offers promising directions for future research. As these innovations continue to evolve, nanofiber-based wound dressings may revolutionize wound care by enabling more personalized and effective treatment strategies.

Background: Recently, regenerative medicine based on cell-based therapies has emerged as a therapeutic possibility for the management of osteoarthritis (OA). Stromal vascular fraction (SVF) is a cellular mixture obtained from lipoaspirate processed through either mechanical or enzymatic separation. SVF has been applied in several countries to treat OA patients without robust supporting evidence or comprehensive evaluation.

Methods: This review purposes to summarize clinical evidence regarding SVF as a therapeutic for OA and to introduce the author's perspective. Eleven studies were found suitable for this review; out of these, seven were randomized clinical trials and four were cohort studies.

Results: A review of controlled studies suggests that SVF may offer better symptomatic relief than placebo or hyaluronic acid in the long term, and the effect of SVF is comparable to that of bone marrow aspirate concentrates.

Conclusion: Prospective studies with improved control over the cell isolation method, dosage, and patient selection are necessary to provide convincing evidence of the benefits of SVF in treating OA.

Background: Effective bone-cartilage integration remains a challenge in orthopedic surgery. Conventional methods often fail to reconstruct the native osteochondral interface. This study explores a scaffold-mediated approach utilizing co-cultured osteoblasts and chondrocytes, with platelet-rich plasma (PRP) as a potential promotor for bone-cartilage interface healing.

Methods: We developed a co-culture system integrating both osteoblasts and chondrocytes on PLGA scaffolds, either with or without PRP supplementation. Cell phenotype maintenance was evaluated by RT-PCR, while morphological analysis was performed by scanning electron microscopy and fluorescence microscopy. To assess healing potential, we created a gap-mimic construct comprising bone, scaffold, and cartilage layers, which was implanted subcutaneously in BALB/c-nude mice. Gap healing was evaluated at 4 and 8 weeks through macroscopic examination, quantitative adhesion analysis, and histological assessment of cellular invasion.

Results: Co-cultured osteoblasts and chondrocytes maintained their phenotypes on PLGA scaffolds, with PRP significantly enhancing cell adhesion (215% increase for chondrocytes, 120% for osteoblasts) and proliferation. In vivo, cell-containing scaffolds demonstrated significantly greater attachment at the bone-cartilage interface compared to acellular constructs. PRP-treated scaffolds exhibited higher attachment rates (82.3% vs 76.7%) and cellular invasion (5/6 vs 3/6 constructs) at 8 weeks, with invasion observed as early as 4 weeks in the PRP group, suggesting accelerated remodeling.

Conclusion: This study demonstrates the feasibility of developing transplantable scaffolds containing co-cultured osteoblasts and chondrocytes while preserving their phenotypes. These scaffolds exhibit significant potential in promoting healing at the bone-cartilage interface, with PRP further enhancing proliferation and improving the scaffold's ability to promote bone-cartilage interface healing.

Background: Choroidal neovascularization (CNV) is a major pathological process underlying retinal degenerative diseases such as wet age-related macular degeneration. While anti-VEGF therapies are widely used, limitations in response and vascular instability necessitate new approaches that promote both antiangiogenic effects and barrier restoration.

Methods: A dual-cell therapy strategy was developed using human umbilical vein endothelial cells (HUVECs) genetically modified to overexpress Tie2 and mesenchymal stem cells (MSCs) engineered to secrete Angiopoietin-1 (Ang1). Antiangiogenic efficacy was evaluated using scratch assays, Transwell migration, and tube formation under VEGF stimulation. A retina-mimetic 2.5D co-culture system incorporating iPSC-derived RPE cells and mCherry-labeled ECs was used to assess endothelial invasion and epithelial barrier preservation.

Results: Tie2/Ang1-modified cells significantly suppressed angiogenic behavior. Transwell migration showed OD595 crystal violet absorbance decreased from 3.54 ± 0.27 (control HUVEC) to 1.28 ± 0.08 (Tie2 overexpressed HUVEC in MSC Ang1 conditioned medium) under VEGF stimulation (p < 0.01). Tube formation area cultured in VEGF dropped from 1.25 ± 0.05 in control group to 0.74 ± 0.07 in Tie2 overexpressed group cultured with MSC-Ang1 conditioned medium (p < 0.01). In the retina-mimetic model, EC infiltration to the RPE monolayer across Transwell membrane decreased from 52.2 ± 8.5% in control HUVEC to 5.6 ± 4.3% with HUVEC-Tie2 + Ang1 conditioned medium under VEGF (p < 0.001).

Conclusion: This study demonstrates that co-delivery of Ang1 and Tie2 via engineered ECs and MSCs synergistically inhibits VEGF-induced angiogenesis and choroidal migration while protecting epithelial barrier function. The retina-mimetic co-culture platform further validates the translational relevance of this dual-cell approach as a regenerative and antiangiogenic strategy in retinal vascular disease.