Enhance Tissue Regeneration Research Articles

Multifunctional Zinc Oxide/Silver Bimetallic Nanomaterial-Loaded Nanofibers for Enhanced Tissue Regeneration and Wound Healing.

Native skin repair requires wound care products that not only protect the wound from bacterial infection, but also accelerate wound closure and minimize scarring. Nanomaterials have been widely applied for wound healing due to their multifunctional properties. In a previous study, we prepared and characterized electrospinning zinc oxide/silver/polyvinylpyrrolidone/polycaprolactone (ZnO/Ag/PVP/PCL) nanofibers using ZnO and Ag nanoparticles, and evaluated their antibacterial effect in vitro. In this work, further characterization studies were performed, which confirmed that the ZnO/Ag nanoparticles were physically embedded and evenly distributed in the ZnO/Ag/PVP/PCL nanofibers, enabling the sustained release of Ag and Zn. In addition, the bimetallic nanofibers showed satisfactory fluid handling and flexibility. In vivo wound healing and histology studies showed that the ZnO/Ag/PVP/PCL nanofibers had a better anti-inflammatory, skin tissue regeneration, and wound healing effect than monometallic nanofibers or a commercially available wound plaster (Yunnan Baiyao). Therefore, ZnO/Ag/PVP/PCL bimetallic nanofibers may be a safe, efficient biomedical dressing for wound healing.

Biodegradable and biocompatible graphene-based scaffolds for functional neural tissue engineering: A strategy approach using dental pulp stem cells and biomaterials.

Neural tissue engineering aims to restore the function of nervous system tissues using biocompatible cell-seeded scaffolds. Graphene-based scaffolds combined with stem cells deserve special attention to enhance tissue regeneration in a controlled manner. However, it is believed that minor changes in scaffold biomaterial composition, internal porous structure, and physicochemical properties can impact cellular growth and adhesion. The current work aims to investigate in vitro biological effects of three-dimensional (3D) graphene oxide (GO)/sodium alginate (GOSA) and reduced GOSA (RGOSA) scaffolds on dental pulp stem cells (DPSCs) in terms of cell viability and cytotoxicity. Herein, the effects of the 3D scaffolds, coating conditions, and serum supplementation on DPSCs functions are explored extensively. Biodegradation analysis revealed that the addition of GO enhanced the degradation rate of composite scaffolds. Compared to the 2D surface, the cell viability of 3D scaffolds was higher (p < 0.0001), highlighting the optimal initial cell adhesion to the scaffold surface and cell migration through pores. Moreover, the cytotoxicity study indicated that the incorporation of graphene supported higher DPSCs viability. It is also shown that when the mean pore size of the scaffold increases, DPSCs activity decreases. In terms of coating conditions, poly- l-lysine was the most robust coating reagent that improved cell-scaffold adherence and DPSCs metabolism activity. The cytotoxicity of GO-based scaffolds showed that DPSCs can be seeded in serum-free media without cytotoxic effects. This is critical for human translation as cellular transplants are typically serum-free. These findings suggest that proposed 3D GO-based scaffolds have favorable effects on the biological responses of DPSCs.

Engineering Bioactive Scaffolds for Skin Regeneration.

Large skin wounds pose a major clinical challenge. Scarcity of donor site and postsurgical scarring contribute to the incomplete or partial loss of function and aesthetic concerns in skin wound patients. Currently, a wide variety of skin grafts are being applied in clinical settings. Scaffolds are used to overcome the issues related to the misaligned architecture of the repaired skin tissues. The current review summarizes the contribution of biomaterials to wound healing and skin regeneration and addresses the existing limitations in skin grafting. Then, the clinically approved biologic and synthetic skin substitutes are extensively reviewed. Next, the techniques for modification of skin grafts aiming for enhanced tissue regeneration are outlined, and a summary of different growth factor delivery systems using biomaterials is presented. Considering the significant progress in biomaterial science and manufacturing technologies, the idea of biomaterial-based skin grafts with the ability for scarless wound healing and reconstructing full skin organ is more achievable than ever.

Genipin guides and sustains the polarization of macrophages to the pro-regenerative M2 subtype via activation of the pSTAT6-PPAR-gamma pathway

M2 macrophages are associated with deposition of interstitial collagen and other extracellular matrix proteins during the course wound healing and also inflammatory response to biomaterials. Developing advanced biomaterials to promote the M2 subtype may be an effective way to improve tissue reinforcement surgery outcomes. In this study, the effect of genipin, a naturally derived crosslinking agent, on M0 → M2-polarization was investigated. Genipin was introduced either indirectly by seeding cells on aligned collagen biotextiles that are crosslinked by the agent or in soluble form by direct addition to the culture medium. Cellular elongation effects on macrophage polarization induced by the collagen biotextile were also investigated as a potential inducer of macrophage polarization. M0 and M2 macrophages demonstrated significant elongation on the surface of aligned collagen threads, while cells of the M1 subtype-maintained a round phenotype. M0 → M2 polarization, as reflected by arginase and Ym-1 production, was observed on collagen threads only when the threads were crosslinked by genipin, implicating genipin as a more potent inducer of the regenerative phenotype compared to cytoskeletal elongation. The addition of genipin to the culture medium directly also drove the emergence of pro-regenerative phenotype as measured by the markers (arginase and Ym-1) and through the activation of the pSTAT6-PPAR-gamma pathway. This study indicates that genipin-crosslinked collagen biotextiles can be used as a delivery platform to promote regenerative response after biomaterial implantation. Statement of significanceThe immune response is one of the key determinants of tissue repair and regeneration rate, and outcome. The M2 macrophage subtype is known to resolve the inflammatory response and support tissue repair by producing pro-regenerative factors. Therefore, a biomaterial that promotes M2 sub-type can be a viable strategy to enhance tissue regeneration. In this study, we investigated genipin-crosslinked electrochemically aligned collagen biotextiles for their capacity to induce pro-regenerative polarization of M0 macrophages. The results demonstrated that genipin, rather than matrix-induced cellular elongation, was responsible for M0 → M2 polarization in the absence of other bioinductive factors and maintaining the M2 polarized status of macrophages. Furthermore, we identified that genipin polarizes the M2 macrophage phenotype via activation of the pSTAT6-PPAR-gamma pathway.

A dual-drug enhanced injectable hydrogel incorporated with neural stem cells for combination therapy in spinal cord injury

Neuronal loss and the formation of glial scars are major pathological events that hinder axonal regrowth and neural regeneration after severe spinal cord injury (SCI). Therapeutic therapies that include both cell transplantation and reducing glial scarring is likely required to achieve substantial functional recovery after severe SCI. In this study, a dual-drug enhanced injectable hydrogel was designed and combined with neural stem cells (NSCs-cfGel) to enhance tissue regeneration in a rat complete transected SCI model. The injectable hydrogel was crosslinked by reversible hydrazone bonds, and the mechanical properties and degradation abilities were analyzed both in vitro and in vivo. When incorporated with two drugs (cetuximab and FTY720), the injectable hydrogel improved both the proliferation and neuronal differentiation and exhibited inhibitory astrocytic differentiation of NSCs in vitro. After transplantation into a rat complete transected SCI model, NSCs-cfGels not only significantly enhanced neuronal differentiation and integration of the grafted NSCs, but also inhibited glial scar formation, and promoted axonal regeneration and nerve circuit reconstruction. Consequently, SCI rats that received NSCs-cfGel implantation exhibited optimal functional improvement. Taken together, this study demonstrates a promising dual-drug enhanced injectable hydrogel for exogenous NSC delivery and thus provides a novel strategy for combination therapy of SCI.

Effects of platelet rich plasma on experimentally induced diabetic heart injury

Diabetic heart is one of the common complications of diabetes mellitus. Platelet-rich plasma (PRP) is an autologous product rich in growth factors that can enhance tissue regeneration. This work was conducted to study the PRP ability to improve diabetes-inducing cardiac changes. Also, it sheds more light on the possible mechanisms through which PRP induces its effects. Rats were divided into; control, PRP, diabetic, and PRP-diabetic groups. Cardiac specimens were obtained and processed for biochemical, histological, and immunohistochemical study. The diabetic group exhibited a significant increase in cardiac oxidative stress, inflammation, and cardiac injury markers if compared with the control group. Additionally, the cardiac tissue showed variable morphological changes in the form of focal distortion and loss of cardiac myocytes. Distorted mitochondria and heterochromatic nuclei were observed in the cardiac muscle fibers. The mean number of charcoal-stained macrophages, and mean area fraction for collagen fibers, mean number of PCNA-immune positive cardiac muscle were significantly decrease in PRP- diabetic group. Collectively, the results showed that PRP treatment ameliorated most of all these previous changes. ConclusionPRP ameliorated the diabetic cardiac injury via inhibition of oxidative stress and inflammation. It was confirmed by biochemical, histological, and immunohistochemical study. It could be concluded that PRP could be used as a potential therapy for diabetic heart.

Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation

BackgroundThe major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear.MethodsGain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA).ResultsCXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs.ConclusionsCXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.

Development of chitosan-based bio-composited materials as a potential wound healing bandage in nursing care of caesarean section: In vivo evaluations

Now-a-days wound healing is a complex biological process without suitable natural biomaterials. Majority of wound dressing scaffolds were made of synthetic biomaterials which has least tendency to mimic natural tissues. In addition, the biocompatibility, biodegradation and mechanical strength of a many bio-composite doesn't possess antibacterial property. To overcome this notable properties and performance, we fabricated a unique multifunctional chitosan/gelatin/ZnO based scaffold bio-composite using freeze drying method. The newly developed scaffolds were characterized using Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and Scanning Electron Microscopy. Further, the biological and mechanical properties of porous scaffold had good biocompatibility and tensile strength. As shown in cell viability, cell proliferation and cell adhesion were capable of rapid tissue regeneration process. Also antibacterial, invitro and invivo results revealed the scaffolds had a strong barrier protection. In results, our scaffold bio-composite showed good microporous structure, enhance tissue regeneration and enhance oxygen permeability at wound site.

A study focused on macrophages modulation induced by the Polymeric Electrospun Matrices (EL-Ms) for application in tissue regeneration: In vitro proof of concept

A successful regenerative process has to consider the role of immune system after surgical implantation of a polymer-based matrix due to the reaction of monocytes and macrophages cells after contact with biomaterial. Pro-inflammatory (TNF-alfa, IL-6 and IL-8) and anti-inflammatory (IL-10) cytokines released by macrophages cells are fundamental in acute inflammatory response (2–3 days) to destroy pathogens and help scaffold during regenerative process supporting the up-regulation of ECM and endothelial progenitor cells.Aim of this work was to evaluate the in vitro acute response induced by pre-optimized polymeric electrospun matrices (EL-Ms), after 3 days contact with macrophages (M0) and EL-Ms ability to modulate M1 and/or M2 macrophages polarization.Biological characterization included MTT, LDH and Live/Dead assays, immunological characterization by ELISA for cytokine-expression levels determination. Morphological characterization was carried out by Confocal Laser Scanning Microscopy and Scanning Electron Microscopy.The results showed an initial pro-inflammatory response (after 24 h) characterized by release of TNF-alfa, IL-6 and IL-8 cytokines. A preferential anti-inflammatory response was highlighted after 72 h, demonstrated by higher release of IL-10 and elongation of macrophages in contact with EL-Ms, that is typical of M2 cell polarization.EL-Ms could be used as eligible support to enhance tissue regeneration promoting an anti-inflammatory response.

Computational modelling of stem cell-niche interactions facilitates discovery of strategies to enhance tissue regeneration and counteract ageing.

The stem cell niche is a specialized microenvironment for stem cells in an adult tissue. The niche provides cues for the maintenance and regulation of stem cell activities and thus presents a target for potential rejuvenating strategies. García‐Prat et al. found that in the heterogeneous population of quiescent stem cells of skeletal muscles, a fraction of cells responsible for regeneration and having genuine ‘stemness’ properties deteriorates only in extremely old age. An essential tool used in this analysis of stem cell–niche interactions is the computational tool, NicheHotSpotter, which proved to be instrumental for identifying niche and cell signalling factors that contribute to the maintenance of the pool of genuine quiescent stem cells. NicheHotSpotter predicts candidate factors by analysing signalling interactome and gene regulatory network data in combination with expression profiles. The effect of the niche environment on stem cells is modelled as a mean field of niche cues that induce sustained activation or inhibition of signalling pathways. In this way, NicheHotSpotter has been successful in delineating novel strategies to enhance stemness, which may rejuvenate skeletal muscle cells at the extreme old age.

A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration

Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.

Antimicrobial and enzyme-responsive multi-peptide surfaces for bone-anchored devices

Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e., non-responsive to biological cues. However, tissue remodeling necessary for implant integration features an ever-changing milieu of cells that demands a responsive biomaterial surface for temporal synchronization of interactions between biomaterial and tissue. Here, we successfully synthesized a multi-functional, dynamic coating on titanium by co-immobilizing GL13K antimicrobial peptide and an MMP-9 – a matrix metalloproteinase secreted by bone-remodeling osteoclasts – responsive peptide. Our co-immobilized peptide surface showed potent anti-biofilm activity, enabled effective osteoblast and fibroblast proliferation, and demonstrated stability against a mechanical challenge. Finally, we showed peptide release was triggered for up to seven days when the multi-peptide coatings were cultured with MMP-9-secreting osteoclasts. Our MMP-9 cleavable peptide can be conjugated with osteogenic or immunomodulatory motifs for enhanced bone formation in future work. Overall, we envisage our multifunctional, dynamic surface to reduce infection rates of percutaneous bone-anchored devices via strong anti-microbial activity and enhanced tissue regeneration via temporal synchronization between biomaterial cues and tissue responses.

Biodegradable multifunctional bioactive Eu-Gd-Si-Ca glass nanoplatform for integrative imaging-targeted tumor therapy-recurrence inhibition-tissue repair

• A multifunctional bioactive tumor imaging-targeted therapy-repair nanoplatform was constructed. • The nanoplatform showed targeted tumor imaging and therapy. • The nanoplatform efficiently inhibited tumor recurrence and enhanced tissue regeneration. The postoperative tissue healing of tumor excision, monitoring of remained tumor cells and inhibiting of tumor recurrence are still the great challenge. Herein, we develop a multifunctional biodegradable silicon-based Eu-Gd-Si-Ca bioactive glass nanoplatform (MBSGN) for tumor imaging, inhibiting tumor recurrence and enhancing tumor-impaired tissue regeneration. MBSGN exhibited a branched mesoporous structure (10–20 nm), controlled biodegradation, ultrahigh drug loading (602.52 mg g −1 ) and pH responsive release behavior, special magneto-optical properties and tumor cell-targeted surface. MBSGN possessed excellent biocompatibility and tumor cell-targeted capacity in vitro . MBSGN showed multi-model bioimaging capacity for skin tumor tissue (fluorescence/magnetic resonance/computed tomography imaging). MBSGN could efficiently eliminate the tumor growth, inhibit the local tumor recurrence through in situ removal of residual tumor cells, greatly enhance the full-thickness wound healing and tumor surgery-caused wounds repair. This study offers a reasonable and promising pathway for in situ integration of multi-modal bio-imaging, recurrent melanoma therapy and tissue regeneration.

Osteogenic Peptides and Attachment Methods Determine Tissue Regeneration in Modified Bone Graft Substitutes.

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field.

Characterisation of Novel Angiogenic and Potent Anti-Inflammatory Effects of Micro-Fragmented Adipose Tissue.

Adipose tissue and more specifically micro-fragmented adipose tissue (MFAT) obtained from liposuction has recently been shown to possess interesting medicinal properties whereby its application supports pain reduction and may enhance tissue regeneration particularly in osteoarthritis. Here we have characterised samples of MFAT produced using the Lipogems® International Spa system from eight volunteer individuals in order to understand the critical biological mechanisms through which they act. A variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units. Almost all of the isolated cells were CD105/CD90/CD45+ indicating stemness. An analysis of the secretions of cytokines from MFAT samples in a culture using targeted arrays and an enzyme-linked immunosorbent assay (ELISA) showed a long-term specific and significant expression of proteins associated with anti-inflammation (e.g., interleukin-1 receptor alpha (Il-1Rα) antagonist), pro-regeneration (e.g., hepatocyte growth factor), anti-scarring and pro-angiogenesis (e.g., transforming growth factor beta 1 and 2 (TGFβ1/2) and anti-bacterial (e.g., chemokine C-X-C motif ligand-9 (CXCL-9). Angiogenesis and angiogenic signalling were notably increased in primary bovine aortic endothelial cells (BAEC) to a different extent in each individual sample of the conditioned medium whilst a direct capacity of the conditioned medium to block inflammation induced by lipopolysaccharides was shown. This work characterises the biological mechanisms through which a strong, long-lasting, and potentially beneficial effect can be observed regarding pain reduction, protection and regeneration in osteoarthritic joints treated with MFAT.

Epidermal and fibroblast growth factors incorporated polyvinyl alcohol electrospun nanofibers as biological dressing scaffold

In this study, single, mix, multilayer Polyvinyl alcohol (PVA) electrospun nanofibers with epidermal growth factor (EGF) and fibroblast growth factor (FGF) were fabricated and characterized as a biological wound dressing scaffolds. The biological activities of the synthesized scaffolds have been verified by in vitro and in vivo studies. The chemical composition finding showed that the identified functional units within the produced nanofibers (O–H and N–H bonds) are attributed to both growth factors (GFs) in the PVA nanofiber membranes. Electrospun nanofibers' morphological features showed long protrusion and smooth morphology without beads and sprayed with an average range of 198–286 nm fiber diameter. The fiber diameters decrement and the improvement in wettability and surface roughness were recorded after GFs incorporated within the PVA Nanofibers, which indicated potential good adoption as biological dressing scaffolds due to the identified mechanical properties (Young’s modulus) in between 18 and 20 MPa. The MTT assay indicated that the growth factor release from the PVA nanofibers has stimulated cell proliferation and promoted cell viability. In the cell attachment study, the GFs incorporated PVA nanofibers stimulated cell proliferation and adhered better than the PVA control sample and presented no cytotoxic effect. The in vivo studies showed that compared to the control and single PVA-GFs nanofiber, the mix and multilayer scaffolds gave a much more wound reduction at day 7 with better wound repair at day 14–21, which indicated to enhancing tissue regeneration, thus, could be a projected as a suitable burn wound dressing scaffold.

Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction.

Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 107 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.

Stimuli-responsive biomaterials for cardiac tissue engineering and dynamic mechanobiology.

Since the term “smart materials” was put forward in the 1980s, stimuli-responsive biomaterials have been used as powerful tools in tissue engineering, mechanobiology, and clinical applications. For the purpose of myocardial repair and regeneration, stimuli-responsive biomaterials are employed to fabricate hydrogels and nanoparticles for targeted delivery of therapeutic drugs and cells, which have been proved to alleviate disease progression and enhance tissue regeneration. By reproducing the sophisticated and dynamic microenvironment of the native heart, stimuli-responsive biomaterials have also been used to engineer dynamic culture systems to understand how cardiac cells and tissues respond to progressive changes in extracellular microenvironments, enabling the investigation of dynamic cell mechanobiology. Here, we provide an overview of stimuli-responsive biomaterials used in cardiovascular research applications, with a specific focus on cardiac tissue engineering and dynamic cell mechanobiology. We also discuss how these smart materials can be utilized to mimic the dynamic microenvironment during heart development, which might provide an opportunity to reveal the fundamental mechanisms of cardiomyogenesis and cardiac maturation.

100 Years of Exploiting Diet and Nutrition for Tissue Regeneration.

In this forum piece, we review progress in exploiting diet and nutrition for enhancing tissue regeneration with a particular emphasis on how dietary composition and diet-induced physiology influence adult stem cell biology.

Enhancement of Wound Healing by Conditioned Medium of Adipose-Derived Stromal Cell with Photobiomodulation in Skin Wound.

Background and ObjectivesThe objective of this study was to investigate whether conditioned medium from photobiomodulation (PBM) irradiated adipose-derived stromal cell (ASC) spheroids prior to implanting could stimulate angiogenesis and tissue regeneration to improve functional recovery of skin tissue in an animal skin wound model.Methods and ResultsASC were split and seeded on chitosan-coated 24 well plate at a density of 7.5×104 cells/cm2, and allowed to adhere at 37℃. Within 3 days of culture, ASC formed spheroids by PBM irradiation. Conditioned medium (CM) fractions were collected from the PBM-ASC to yield nor adipose-derived stromal cell spheroid (spheroid) and PBM-spheroid, respectively, centrifuged at 13,000 g at 4℃ for 10 min, and stored prior to use for ELISA, protein assay, or in vivo wound-healing assays. Phosphate-buffered saline, cultured CM from ASCs, PBM irradiation prior to implanting conditioned medium from ASC, cultured CM from ASC spheroid, and PBM–spheroid-CM (PSC) were transplanted into a wound bed in athymic mice to evaluate therapeutic effects of PSC in vivo. PSC enhanced wound closure in a skin injury model compared to PBS, CM, PBM–CM, and spheroid-CM. The density of vascular formations increased as a result of angiogenic factors released by the wound bed and enhanced tissue regeneration at the lesion site.ConclusionsThese results indicate that implant of PSC can significantly improve functional recovery compared to PBS, CM, PBM–CM, or spheroid-CM treatment. Implant of PSC may be an effective form of paracrine mediated therapy for treating a wound bed.