Tissue Regeneration Research Articles

Sr-Mg co-doped Hardystonite/Polycaprolactone electrospun scaffolds: Fabrication and Characterization for enhanced bone regeneration

The production of scaffolds is a primary objective in tissue engineering for treating bone defects and diseases. The electrospinning process offers a promising technique to create structures resembling the extracellular matrix. Artificial polymeric grafts, such as poly(caprolactone) (PCL), often face issues of low strength and degradation. To overcome these limitations, we introduce ceramic reinforcing particles, specifically hardystonite (Ca2ZnSi2O7), known for its benefits in tissue regeneration. Considering the undeniable role of strontium and magnesium in bone regeneration, the aim of this study was to investigate and compare produced scaffolds with and without dopant elements, incorporated into hardystonite. Initially, strontium-magnesium-doped hardystonite (DHT) nanopowder was synthesized through mechanical milling followed by thermal treatment. The successful formation of a single-phase hardystonite structure was verified by X-ray diffraction (XRD), with estimated crystallite and particle sizes of approximately 41.6nm and 77.23 ± 36.60 nm, respectively. Subsequently, PCL/DHT composite scaffolds were fabricated with 3 wt%, 5 wt%, and 10 wt% bioceramic content. These scaffolds were assessed for fiber morphology, physical and chemical properties, hydrophilicity, surface roughness, mechanical characteristics, degradation, and biocompatibility. The results indicate that PCL/5 wt% DHT scaffolds exhibit superior biological, physical, and mechanical properties. Across all these tests, the PCL/5 wt% DHT scaffold consistently outperformed the others, suggesting its promising potential in bone tissue engineering.

The elemental variance between the "rice" and "non-rice" portions of Maifanitum and its health risk assessment

BackgroundMaifanitum, a mineral used in Chinese medicine, was first documented during the Song Dynasty (960-1279). Historical records suggest its multifaceted therapeutic properties, including detoxification and stasis resolution, necrosis removal and tissue regeneration, diuretic and calculi dissolution and prolonging life. The concentration of elements in Maifanitum may vary depending on its origin, different parts, which can affect its effectiveness in different fields of applications. Therefore, the analysis of elements in Maifanitum and the subsequent health risk assessment have been conducted. This provides an important basis for the quality control and application safety of Maifanitum. MethodThe analytical techniques employed in this study are inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES), utilized for the quantitative assessment of 60 elements (Refer to Appendix 1) within Maifanitum samples. Based on the test results, chemometric methods are employed to evaluate the characteristics and differences in elemental concentration from different sources and locations. Additionally, a preliminary health risk assessment is conducted for Maifanitum from different origins and various parts. ResultsWe have established a fingerprint of the elements within Maifanitum, demonstrating a commendable level of similarity. The findings from hierarchical cluster analysis（HCA） corroborated with those from principal component analysis (PCA), collectively unveiling a systematic profile of elemental disparities between Maifanitum samples of diverse origins and applications. It also revealed that there are differences in the concentration of Al, Ga, Be, Hf, Na, Sn, Ti, Zr, Gd, Tb, Sr, Pb, Ce, Ba and other elements in different parts of Maifanitum. While Cd, As, and Cu levels in all samples were within the permissible limits as defined by the Chinese Pharmacopeia, Pb concentrations in the majority of samples were found to surpass these standards, albeit slightly in the ''non-rice'' fraction. The assessment of both beneficial and deleterious elements indicates that the ''non-rice'' fraction of Maifanitum possesses superior quality attributes. Moreover, the overall concentration of rare earth elements in Maifanitum is substantially below the established lower threshold for daily human consumption, with no immediate evidence suggesting any adverse health risks. ConclusionThis study provides a basis for the quality control and safety evaluation of Maifanitum in clinical use.

Efficacy and Safety of Cell-Assisted Acellular Adipose Matrix Transfer for Volume Retention and Regeneration Compared to Hyaluronic Acid Filler Injection.

Cell-assisted acellular adipose matrix (AAM) transfer is a novel technique for soft tissue volume restoration, where AAM acts as a scaffold for tissue proliferation and promotes host cell migration, vascularization, and adipogenesis. This study aimed to evaluate the efficacy and safety of in vivo cell-assisted AAM transfer compared to hyaluronic acid (HA) filler injection. Human adipose tissue was used to manufacture AAM, and murine adipose-derived stem cells (ASCs) were prepared. Nude mice were divided into four groups: AAM transfer (AT), ASC-assisted AAM transfer (CAT), HA filler injection (HI), and ASC-assisted HA filler injection (CHI). Eight weeks post-transfer, in vivo graft volume/weight, histology, and gene expression were analyzed to assess efficacy and safety. The AAM retained its three-dimensional scaffold structure without cellular components. AT/CAT showed lower volume retention than HA/CHA; however, CAT maintained a similar volume to HA. Histologically, adipogenesis and collagen formation were increased in AT/CAT compared to HA/CHA, with CAT showing the highest levels. CAT also demonstrated superior angiogenesis, adipogenesis, and gene expression (Vegf and Pparg), along with lower Il-6 expression, higher Il-10 expression, and reduced capsule formation, indicating better biocompatibility. Cell-assisted AAM transfer is a promising technique for volume retention and tissue regeneration, offering a safe and effective alternative to HA filler injections. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Research progress on iron metabolism in the occurrence and development of periodontitis

Iron metabolism refers to the process of absorption, transport, excretion and storage of iron in organisms, including the biological activities of iron ions and iron-binding proteins in cells. Clinical research and animal experiments have shown that iron metabolism is associated with the progress of periodontitis. Iron metabolism not only enhances the proliferation and toxicity of periodontal pathogens, but also activate host immune-inflammatory response mediated by macrophages, neutrophils and lymphocytes. In addition, iron metabolism is also involved in regulating cellular death sensitivity of gingival fibroblasts and osteoblasts and promoting the differentiation of osteoclasts, which plays a regulatory role in the regeneration and repair of periodontal tissue. This article reviews the research progress on the pathogenesis of periodontitis from the perspective of iron metabolism, aiming to provide new ideas for the treatment of periodontitis.

Simultaneous processing of both handheld biomixing and biowriting of kombucha cultured pre-crosslinked nanocellulose bioink for regeneration of irregular and multi-layered tissue defects

The nanocellulosic pellicle derived from the symbiotic culture of bacteria and yeast (Kombucha SCOBY) is an important biomaterial for 3D bioprinting in tissue engineering. However, this nanocellulosic hydrogel has a highly entangled gel network. This needs to be partially modified to improve its processability and extrusion ability for its applications in the 3D bioprinting area. To control its mechanical and biological properties for direct 3D bioprinting applications, uniform reinforcement of nanocellulose-interacting polymers and nanoparticles in such a prefabricated gel network is essential. In this study, the hydrogel network is partially hydrolyzed with organic acid and subsequently transformed into a 3D bioprintable polyelectrolyte complex with chitosan and kaolin nanoparticles without any chemical crosslinker using a handheld 3D bioprinter. This handheld bioprinter ensures homogeneity in both biomixing and bioprinting of chitosan and kaolin within the modified nanocellulose network for multi-layered bioprinted scaffolds through an extensional shear mechanism. The biomixing simulation, mechanical (static, dynamic, and cyclic), 3D bioprinting, and cellular studies confirm the homogeneous biomixing of kaolin nanoparticles and live cells in this nanocellulose-chitosan polyelectrolyte hydrogel. The combination of SCOBY-derived nanocellulose-chitosan bioink with kaolin nanoparticles and a screw-driven handheld extrusion bioprinter demonstrates a promising platform for layer-by-layer regeneration of complex tissues with homogeneous cell/particle distribution with high cell viability.

Mini Review: Challenges and Promising Advances in Hydrogel‐Based Scaffolds for Breast Tissue Regeneration

ABSTRACTThe loss of breast tissue is a problem that plagues many women. Total mastectomy procedures after breast cancer or extensive tissue loss by accident generate permanent aesthetic‐functional lesions that are correlated with the loss of breastfeeding capacity, loss of self‐esteem, anxiety, depression, reduced sexual attraction, hopelessness, and often, suicide. Although current clinical practices try to restore aesthetics, functional improvements are not readily resolved by these maneuvers. Those who undergo such procedures often end up with permanent aesthetic and functional injuries. The difficulty in regenerating breast tissue stems from its high structural complexity. In cases of extensive loss of breast tissue, the use of regeneration strategies becomes necessary for proper healing and tissue reconstruction. In this context, the use of regeneration scaffolds may open new possibilities for the regeneration of various body tissues, especially breast tissue, enabling the adequate healing of large injuries in different tissues. Hydrogels are examples of highly versatile materials for this application, given the range of methodologies for their preparation and composition components. The results of various studies indicate that the application of hydrogel‐based scaffolds for breast regeneration is highly promising. Among the materials and systems most applied for this purpose, biodegradable polymers stand out due to their high biocompatibility and the ability for spontaneous removal from the organism. In this sector, systems obtained through 3D printing also stand out due to the increased predictability of geometry and pore distribution. However, it is noteworthy that the evaluated regeneration systems are primarily focused on regenerating adipose tissue, with no specific systems for the epithelial regeneration of the breasts or the areas of glandular tissue. These areas represent sectors that still need further exploration.

Clinical utility of extracorporeal shock wave therapy in restoring hand function of patients with nerve injury and hypertrophic scars due to burns: A prospective, randomized, double-blinded study.

Joint contractures and nerve injuries are common after hand burns. Extracorporeal shock wave therapy (ESWT) is effective not only for the regeneration of various tissues, including scar tissues, but also for reducing pain and pruritus in patients with burns. Researchers have attempted to explore the effects of ESWT on hand dysfunction caused by nerve injury following burns. We evaluated the effects of ESWT (compared to sham stimulation) on hands with nerve injury and hypertrophic scars and thereby on hand function. The current study was a double-blind randomized controlled trial involving 120 patients. The ESWT parameters were as follows: energy flux density, 0.05-0.30mJ/mm2; frequency, 4Hz; 1000 to 3000 impulses per treatment; and 12 treatments, one/week for 12 weeks. Outcome measures were as follows: 10-point visual analog scale for pain, Jebsen-Taylor hand function test, grip strength, Purdue Pegboard test, ultrasound measurement of scar thickness, and skin characteristics before and immediately after 12 weeks of treatment. No significant inter-group difference was noted after the initial evaluation (P>0.05). More significant improvements were found in the ESWT group than in the sham group in terms of the VAS score (P=0.004), extension ROMs of hand joints (P=0.02), the JTT scores (writing, small, and light) (P<0.001, P<0.001, and P=0.002), and skin characteristics (melanin, skin distensibility, and biologic skin elasticity) (P=0.004, P<0.001, and P<0.001). Other measured outcomes did not differ between the two groups after the treatment. We identified the clinically beneficial effects of ESWT in promoting hand function, improving scarring, and alleviating scarring-related pain, thereby highlighting its advantages in improving hand function that has been impaired due to nerve injury and hypertrophic scars after burns.

Preparation of recombinant type I collagen (PF-I-80) and its functional characterization and biomedical applications in wound healing

This study evaluates the potential applications of recombinant PF-I-80 protein in regenerative medicine and the treatment of inflammatory diseases, focusing on its effects on cell migration, differentiation, and anti-inflammatory properties. Various in vitro assays were conducted, including scratch assays, Transwell experiments, RT-PCR and Western Blot to analyze gene and protein expression related to differentiation and inflammation, and immunofluorescence staining to observe cellular changes. The results indicated that PF-I-80 significantly promoted cell migration, highlighting its potential in tissue repair and regeneration. It also enhanced cell differentiation, demonstrating its applicability in tissue repair, and showed significant anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines. In animal models, PF-I-80 notably reduced levels of inflammatory factors IL-1β and TNF-α, shortened the inflammatory phase, and accelerated wound healing. Additionally, PF-I-80 increased FGF-2 levels, which promoted the proliferation of endothelial and fibroblast cells and enhanced collagen synthesis. These in vitro and in vivo findings position PF-I-80 as a promising biomaterial for applications in regenerative medicine and inflammatory disease treatment.

The Angiogenic Repertoire of Stem Cell Extracellular Vesicles: Demystifying the Molecular Underpinnings for Wound Healing Applications.

Stem cells-derived extracellular vesicles (SC-EVs) have emerged as promising therapeutic agents for wound repair, recapitulating the biological effects of parent cells while mitigating immunogenic and tumorigenic risks. These EVs orchestrate wound healing processes, notably through modulating angiogenesis-a critical event in tissue revascularization and regeneration. This study provides a comprehensive overview of the multifaceted mechanisms underpinning the pro-angiogenic capacity of EVs from various stem cell sources within the wound microenvironment. By elucidating the molecular intricacies governing their angiogenic prowess, we aim to unravel the mechanistic repertoire underlying their remarkable potential to accelerate wound healing. Additionally, methods to enhance the angiogenic effects of SC-EVs, current limitations, and future perspectives are highlighted, emphasizing the significant potential of this rapidly advancing field in revolutionizing wound healing strategies.

Engineering Microgel Packing to Tailor the Physical and Biological Properties of Gelatin Methacryloyl Granular Hydrogel Scaffolds.

Granular hydrogel scaffolds (GHS) are fabricated via placing hydrogel microparticles (HMP) in close contact (packing), followed by physical and/or chemical interparticle bond formation. Gelatin methacryloyl (GelMA) GHS have recently emerged as a promising platform for biomedical applications; however, little is known about how the packing of building blocks, physically crosslinked soft GelMA HMP, affects the physical (pore microarchitecture and mechanical/rheological properties) and biological (in vitro and in vivo) attributes of GHS. Here, the GHS pore microarchitecture is engineered via the external (centrifugal) force-induced packing and deformation of GelMA HMP to regulate GHS mechanical and rheological properties, as well as biological responses in vitro and in vivo. Increasing the magnitude and duration of centrifugal force increases the HMP deformation/packing, decreases GHS void fraction and median pore diameter, and increases GHS compressive and storage moduli. MDA-MB-231 human triple negative breast adenocarcinoma cells spread and flatten on the GelMA HMP surface in loosely packed GHS, whereas they adopt an elongated morphology in highly packed GHS as a result of spatial confinement. Via culturing untreated or blebbistatin-treated cells in GHS, the effect of non-muscle myosin II-driven contractility on cell morphology is shown. In vivo subcutaneous implantation in mice confirms a significantly higher endothelial, fibroblast, and macrophage cell infiltration within the GHS with a lower packing density, which is in accordance with the in vitro cell migration outcome. These results indicate that the packing state of GelMA GHS may enable the engineering of cell response in vitro and tissue response in vivo. This research is a fundamental step forward in standardizing and engineering GelMA GHS microarchitecture for tissue engineering and regeneration.

A framework for digital twin integration in biofabrication and a scaffold 3D bioplotting case study

Biofabrication, which integrates biological sciences with advanced manufacturing, is vital for innovations in tissue engineering and regenerative medicine. One primary consideration in this domain is ensuring consistent, scalable, and adaptable processes that are amenable to clinical translation. Toward this, this paper introduces a new framework for digital twin integration in biofabrication. Digital twins, which are real-time virtual replicas of physical systems, can facilitate comprehensive monitoring, accurate prediction, and effective optimization to enable robust biofabrication processes and systems. The proposed framework incorporates major building blocks for implementing digital twins for biofabrication, including comprehensive data acquisition and analysis using sophisticated sensors to integrate biological, material, and process data; advanced modeling methods utilizing traditional and machine learning algorithms to refine process parameters; and feedback loop for real-time process adjustments. The first phase of the framework is demonstrated through a case study highlighting process optimization of 3D bioplotting of polycaprolactone (PCL) scaffolds. The digital twin’s insights streamline decisions on bioplotting parameters and post-processing, ensuring that the printed scaffold meets the desired mechanical and biological properties, thereby significantly enhancing cell proliferation and printing resolution. Key benefits of this approach include optimized biofabrication outcomes by integrating physical and biological models, promoting scalability and reproducibility with an accelerated research and development phase. This work underlines the promise of digital convergence in biofabrication, which can accelerate advancements in regenerative medicine and tissue engineering.

Directed Differentiation of Adipose-Derived Stem Cells Using Imprinted Cell-Like Topographies as a Growth Factor-Free Approach.

The influence of surface topography on stem cell behavior and differentiation has garnered significant attention in regenerative medicine and tissue engineering. The cell-imprinting method has been introduced as a promising approach to mimic the geometry and topography of cells. The cell-imprinted substrates are designed to replicate the topographies and dimensions of target cells, enabling tailored interactions that promote the differentiation of stem cells towards desired specialized cell types. In fact, by replicating the size and shape of cells, biomimetic substrates provide physical cues that profoundly impact stem cell differentiation. These cues play a pivotal role in directing cell morphology, cytoskeletal organization, and gene expression, ultimately influencing lineage commitment. The biomimetic substrates' ability to emulate the native cellular microenvironment supports the creation of platforms capable of steering stem cell fate with high precision. This review discusses the role of mechanical factors that impact stem cell fate. It also provides an overview of the design and fabrication principles of cell-imprinted substrates. Furthermore, the paper delves into the use of cell-imprinted polydimethylsiloxane (PDMS) substrates to direct adipose-derived stem cells (ADSCs) differentiation into a variety of specialized cells for tissue engineering and regenerative medicine applications. Additionally, the review discusses the limitations of cell-imprinted PDMS substrates and highlights the efforts made to overcome these limitations.

Characterization of decellularized porcine oviduct- and uterine-derived scaffolds evaluated by spermatozoa-based biocompatibility and biotoxicity

Extracellular matrix-derived scaffolds (dECM) are widely utilized in regenerative medicine and tissue engineering due to their ability to promote cell growth, proliferation, and differentiation. In reproduction, research is focused on using these scaffolds to treat pathologies causing reproductive dysfunction or to improve assisted reproduction technologies (ARTs). We developed an efficient protocol employing the immersion-agitation technique to decellularize porcine oviductal and uterine sections, comparing the efficacy of fresh versus frozen treatments. Both methods successfully generated acellular matrices with less than 3% residual DNA, effectively preserving structural and protein integrity. Scanning and transmission electron microscopy confirmed the ultrastructural integrity, whereas Masson's Trichrome staining highlighted better collagen preservation in frozen treatments. Proteomic analysis of decellularized scaffolds revealed collagen and key macromolecules such as laminin, filamin, dermatopontin, and fibronectin, which are essential for extracellular matrix structure and cell functions such as adhesion and migration. Innovatively, we assessed the biocompatibility and cytotoxicity of the scaffolds using spermatozoa, demonstrating that thorough washing ensures the scaffold biocompatibility without compromising sperm viability or motility. Our findings not only contribute to the standardization of decellularization protocols for female reproductive organs but also emphasize the importance of evaluating sperm biocompatibility to ensure the safety of dECM scaffolds.

Nanocarrier-Assisted Delivery of Berberine Promotes Diabetic Alveolar Bone Regeneration by Scavenging ROS and Improving Mitochondrial Dysfunction.

Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.

Fabrication and characterization of an electrospun silk fibroin/gelatin transparent graft material for corneal epithelial regeneration

The damaged corneal epithelial causing loss of vision can be restored by epithelial tissue regeneration through tissue engineering approach that provides an engineered corneal substitute with appropriate properties and nanofibrous architecture. This works reports a polymeric matrix that was derived from silk fibroin (SF) and gelatin (GE) natural polymer blend with optimized composition resembling the structure and function of the native epithelial tissue. SF/GE blend spinning solutions prepared with different volume ratios of SF/GE: 70/30, 50/50, and 30/70 were used to fabricate electrospun mats. The fabricated two-dimensional mats had nanofibrous porous architecture having interconnected pores with pore size range of 175–267 nm suitable for corneal epithelial regeneration and 891.2–558 nm fiber diameter range as revealed by scanning electron microscopic image analysis. The performed Fourier transform infrared spectra confirmed the presence of individual polymers in the scaffolds and the scaffolds are hydrophilic in nature. Among the scaffolds, SF/GE 70:30 and SF/GE 50:50 composition possess desired porosity range of 87–88%. The tensile strength was slightly decreased with increase in GE content and the strength obtained was in the range 2.74–2.26 Mpa. An enhanced transparency was obtained with increased GE concentration, the transparency range of 73–82% observed with SF/GE:50/50 matches with the transparency of natural corneal epithelium. The biocompatibility of the scaffolds was confirmed by cell attachment, cytotoxicity and ROS evaluation by culturing rabbit corneal fibroblast cells (SIRC) on the scaffolds. Among the scaffolds, SF/GE: 70/30 exhibited the highest cell viability, but with less transparency ranging 55–71%. Therefore, considering all the properties, SF/GE with 50:50 ratio scaffold may be a suitable substrate in the field of corneal tissue engineering.

EFFECT OF PHYSIOTHERAPY ON THE IMPLANTATION POTENTIAL OF THIN ENDOMETRIUM

The article is dedicated to the urgent problem of infertility associated with thin endometrium. The mechanisms of action of various physiotherapeutic methods on the endometrium, such as magnetotherapy, laser therapy, ultrasound therapy, and electrical stimulation, are discussed. The beneficial effects of physiotherapy are described in detail, including improved blood flow, reduced inflammation, and stimulation of tissue regeneration. The results of clinical trials confirming the effectiveness of physiotherapy in increasing the thickness and improving the structure of the endometrium are presented. The article also includes indications and contraindications for the use of physiotherapy and emphasizes the importance of an individualized approach to treatment.

Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration

Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects in vivo and in vitro. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, in vivo experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration. Statement of Significance: We present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.

Boosting chondrocyte bioactivity with ultra-sulfated glycopeptide supramolecular polymers

Although autologous chondrocyte transplantation can be effective in articular cartilage repair, negative side effects limit the utility of the treatment, such as long recovery times, poor engraftment or chondrogenic dedifferentiation, and cell leakage. Peptide-based supramolecular polymers have emerged as promising bioactive systems to promote tissue regeneration through cell signaling and dynamic behavior. We report here on the development of a series of glycopeptide amphiphile supramolecular nanofibers with chondrogenic bioactivity. These supramolecular polymers were found to have the ability to boost TGFβ-1 signaling by displaying galactosamine moieties with differing degrees of sulfation on their surfaces. We were also able to encapsulate chondrocytes with these nanostructures as single cells without affecting viability and proliferation. Among the monomers tested, assemblies of trisulfated glycopeptides led to elevated expression of chondrogenic markers relative to those with lower degrees of sulfation that mimic chondroitin sulfate repeating units. We hypothesize the enhanced bioactivity is rooted in specific interactions of the supramolecular assemblies with TGFβ-1 and its consequence on cell signaling, which may involve elevated levels of supramolecular motion as a result of high charge in trisulfated glycopeptide amphiphiles. Our findings suggest that supramolecular polymers formed by the ultra-sulfated glycopeptide amphiphiles could provide better outcomes in chondrocyte transplantation therapies for cartilage regeneration. Statement of significanceThis study prepares glycopeptide amphiphiles conjugated at their termini with chondroitin sulfate mimetic residues with varying degrees of sulfation that self-assemble into supramolecular nanofibers in aqueous solution. These supramolecular polymers encapsulate chondrocytes as single cells through intimate contact with cell surface structures, forming artificial matrix that can localize the growth factor TGFβ-1 in the intercellular environment. A high degree of sulfation on the glycopeptide amphiphile is found to be critical in elevating chondrogenic cellular responses that supersede the efficacy of natural chondroitin sulfate. This work demonstrates that supramolecular assembly of a unique molecular structure designed to mimic chondroitin sulfate successfully boosts chondrocyte bioactivity by single cell encapsulation, suggesting a new avenue implementing chondrocyte transplantation with supramolecular nanomaterials for cartilage regeneration.

Guided tissue regeneration for periodontal intrabony defects

Guided tissue regeneration for periodontal intrabony defects

Granulocyte colony stimulating factor promotes scarless tissue regeneration

Granulocyte colony stimulating factor promotes scarless tissue regeneration