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Bone defect is a common clinical orthopedic disease. The trend in this field is to develop tissue engineering scaffolds with appropriately designed components and structures for bone repair. Herein, inspired by the organic and inorganic components of bone matrix and the natural biomineralization mechanism, a MgSiO3@Fe3O4 nanoparticle composite polycaprolactone (PCL) hybrid mineralized scaffold for bone repair is developed by microfluidic 3D printing. The incorporation of MgSiO3@Fe3O4 within the PCL scaffold can effectively improve the bioactivity. In addition, a biomimetic mineralized layer is prepared on the surface of the scaffold, which endowed it with unique microstructural characteristics, enhanced cell adhesion and osteogenic activity, and thus improved the bone repair performance. Owing to these advantages, both in vivo and in vitro experiments have demonstrated that the designed scaffold has outstanding biocompatibility and bone repair performance. These features indicate that the organic–inorganic biomineralized hybrid scaffold can be a potential bone graft substitute for clinical bone repair. [ABSTRACT FROM AUTHOR]

Bone defects resulting from trauma, surgery, and congenital, infectious, or oncological diseases are a functional and aesthetic burden for patients. Bone regeneration is a demanding procedure, involving a spectrum of molecular processes and requiring the use of various scaffolds and substances, often yielding an unsatisfactory result. Recently, the new collagen sponge and its structural derivatives manufactured from European carp (Cyprinus carpio) were introduced and patented. Due to its fish origin, the novel scaffold poses no risk of allergic reactions or transfer of zoonoses and additionally shows superior biocompatibility, mechanical stability, adjustable degradation rate, and porosity. In this review, we focus on the basic principles of bone regeneration and describe the characteristics of an "ideal" bone scaffold focusing on guided bone regeneration. Moreover, we suggest several possible applications of this novel material in bone regeneration processes, thus opening new horizons for further research. [ABSTRACT FROM AUTHOR]

With the graying of the world's population, the morbidity of age-related chronic degenerative bone diseases, such as osteoporosis and osteoarthritis, is increasing yearly, leading to an increased risk of bone defects, while current treatment methods face many problems, such as shortage of grafts and an incomplete repair. Therefore, bone tissue engineering offers an alternative solution for regenerating and repairing bone tissues by constructing bioactive scaffolds with porous structures that provide mechanical support to damaged bone tissue while promoting angiogenesis and cell adhesion, proliferation, and activity. 3D printing technology has become the primary scaffold manufacturing method due to its ability to precisely control the internal pore structure and complex spatial shape of bone scaffolds. In contrast, the fast development of nanotechnology has provided more possibilities for the internal structure and biological function of scaffolds. This review focuses on the application of 3D printing technology in bone tissue engineering and nanotechnology in the field of bone tissue regeneration and repair, and explores the prospects for the integration of the two technologies. [ABSTRACT FROM AUTHOR]

Fragment-based drug design of new bioactive scaffolds is a recent aspect of medicinal chemistry that provides a faster and more efficient road in drug discovery. Phenoxyethyl piperidine and morpholine derivatives have various pharmacological activities, from antitussive to anticancer properties. They are also widely used in selective estrogen receptor modulator (SERM) drugs and can be used to prevent osteoporosis in postmenopausal women. Also, other recent findings suggest that these compounds exhibit high anticholinergic and H3 inverse agonistic activities. We outlined the process of developing novel medications for Alzheimer's disease, malaria, cancer, and various other illnesses, which could entail modifying or incorporating these structures into a different biologically active framework. Pharmacokinetic assessment and organic pathways for synthesizing these scaffolds are also indicated. This review will discuss the recent pharmaceutical advances of phenoxyethyl cyclic amine derivatives in experimental, investigational, and FDA-approved drugs to draw an apparent viewpoint for future drug research and discovery. [ABSTRACT FROM AUTHOR]

The treatment of bone defects is a difficult problem in orthopedics. The excessive destruction of local bone tissue at defect sites destroys blood supply and renders bone regeneration insufficient, which further leads to delayed union or even nonunion. To solve this problem, in this study, we incorporated icariin into alginate/mineralized collagen (AMC) hydrogel and then placed the drug-loaded hydrogel into the pores of a 3D-printed porous titanium alloy (AMCI/PTi) scaffold to prepare a bioactive scaffold with the dual functions of promoting angiogenesis and bone regeneration. The experimental results showed that the ACMI/PTi scaffold had suitable mechanical properties, sustained drug release function, and excellent biocompatibility. The released icariin and mineralized collagen (MC) synergistically promoted angiogenesis and osteogenic differentiation in vitro. After implantation into a rabbit radius defect, the composite scaffold showed a satisfactory effect in promoting bone repair. Therefore, this composite dual-functional scaffold could meet the requirements of bone defect treatment and provide a promising strategy for the repair of large segmental bone defects in clinic.

Quinolines have become essential to many drugs, including broad-spectrum antibiotics, antivirus, antitubercular, and antimalarial agents. Owing to their importance in medicinal and pharmaceutic industries, several studies have been conducted to synthesize new and novel quinoline derivatives and their hybrid compounds with potent biological applications. In this review, we report the recent research involved in the search for biologically active molecules containing quinoline moiety, including their hybrids. The review provides information on advancements in the last ten years in the chemistry of hybrids and derivatives of quinolines. Also, the medicinal impact of some potent patents based on quinoline derivatives is discussed.

Bone defects resulting from trauma, surgery, and congenital, infectious, or oncological diseases are a functional and aesthetic burden for patients. Bone regeneration is a demanding procedure, involving a spectrum of molecular processes and requiring the use of various scaffolds and substances, often yielding an unsatisfactory result. Recently, the new collagen sponge and its structural derivatives manufactured from European carp (Cyprinus carpio) were introduced and patented. Due to its fish origin, the novel scaffold poses no risk of allergic reactions or transfer of zoonoses and additionally shows superior biocompatibility, mechanical stability, adjustable degradation rate, and porosity. In this review, we focus on the basic principles of bone regeneration and describe the characteristics of an “ideal” bone scaffold focusing on guided bone regeneration. Moreover, we suggest several possible applications of this novel material in bone regeneration processes, thus opening new horizons for further research.

The local application of drug‐loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self‐assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone‐related peptide‐1 (PTHrP‐1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti‐OP bone repair material provides a theoretical basis for clinical translational applications. [ABSTRACT FROM AUTHOR]

Background: Functional restoration of the bone-to-tendon interface (BTI) after rotator cuff repair is a challenge. Therefore, numerous biocompatible biomaterials for promoting BTI healing have been investigated. Purpose: To determine the efficacy of scaffolds with spatiotemporal delivery of growth factors (GFs) to accelerate BTI healing after rotator cuff repair. Study Design: Controlled laboratory study. Methods: An advanced 3-dimensional printing technique was used to fabricate bioactive scaffolds with spatiotemporal delivery of multiple GFs targeting the tendon, fibrocartilage, and bone regions. In total, 50 rabbits were used: 2 nonoperated controls and 48 rabbits with induced chronic rotator cuff tears (RCTs). The animals with RCTs were divided into 3 groups: (A) saline injection, (B) scaffold without GF, and (C) scaffold with GF. To induce chronic models, RCTs were left unrepaired for 6 weeks; then, surgical repairs with or without bioactive scaffolds were performed. For groups B and C, each scaffold was implanted between the bony footprint and the supraspinatus tendon. Four weeks after repair, quantitative real-time polymerase chain reaction and immunofluorescence analyses were performed to evaluate early signs of regenerative healing. Histological, biomechanical, and micro–computed tomography analyses were performed 12 weeks after repair. Results: Group C had the highest mRNA expression of collagen type I alpha 1, collagen type III alpha 1, and aggrecan. Immunofluorescence analysis showed the formation of an aggrecan+/collagen II+ fibrocartilaginous matrix at the BTI when repaired with scaffold with GFs. Histologic analysis revealed greater collagen fiber continuity, denser collagen fibers, and a more mature tendon-to-bone junction in GF-embedded scaffolds than those in the other groups. Group C demonstrated the highest load-to-failure ratio, and modulus mapping showed that the distribution of the micromechanical properties of the BTI repaired with GF-embedded scaffolds was comparable with that of the native BTI. Micro–computed tomography analysis identified the highest bone mineral density and bone volume/total volume ratio in group C. Conclusion: Bioactive scaffolds with spatially embedded GFs have significant potential to promote the BTI healing of chronic RCTs in a rabbit model. Clinical Relevance: The scaffolds with spatiotemporal delivery of GF may serve as an off-the-shelf biomaterial graft to promote the healing of RCTs. [ABSTRACT FROM AUTHOR]

Abstract Larval therapy has been reported to be beneficial in the treatment of chronic wounds by promoting granulation tissue formation, due to its antimicrobial properties and by degrading necrotic tissue. However, the use of live maggots is problematic for patient acceptance, and thus there is a need to develop materials which can release therapeutic biomolecules derived from maggot secretions to the wound bed. Here we describe the fabrication of a novel bioactive scaffold that can be loaded with Lucilia sericata maggot alimentary excretion/secretion fluids (L. sericata maggot E/S), and which can also provide structural stability for mammalian cell-growth and migration to support wound repair. Electrospun scaffolds were prepared from a poly(caprolactone)-poly(ethylene glycol)–block copolymer (PCL-b-PEG) blended with PCL with average fibre diameters of ~ 4 μm. The scaffolds were hydrophilic and were able to support viable fibroblasts that were able to infiltrate throughout the extent of the scaffold thickness. L. sericata maggot (E/S) was subsequently adsorbed to the surface and released over 21 days with retention of the protease activity that is responsible for supporting fibroblast migration. The incorporation of L. sericata maggot E/S on the surface of the electrospun fibres of PCL-PEG/PCL fibres is a novel approach with potential for future application to support skin wound healing within a clinical setting.

Abstract The local application of drug‐loaded bioactive scaffold materials is one of the important directions to solve the clinical problem of osteoporotic (OP) bone defects. This study retains the advantages of drug loading and mechanical properties of natural 3D bioactive scaffolds. The scaffolds are functionally modified through chemical and self‐assembly approaches with application of polydopamine (PDA) nanoparticles and parathyroid hormone‐related peptide‐1 (PTHrP‐1) for efficient local drug loading. This study investigates the effects of the novel bioactive scaffolds on ossification, osteoclastogenesis, and macrophage polarization. This work elucidates the effects of the scaffolds in regulating osteoclastic activity and new bone formation in vitro. Further studies on the establishment and repair of OP bone defects in small animals are conducted, and the potential of natural bioactive porous scaffold materials to promote the repair of OP bone defects is initially verified. The preparation of safe and economical anti‐OP bone repair material provides a theoretical basis for clinical translational applications.

Introduction: complicated skin injuries have become a global health problem, being difficult to treat due to the body’s limited healing process. Many studies aim to enhance traditional treatments for skin injuries, which have many disadvantages. Therefore, wound healing research is aiming towards tissue engineering options, such as decellularized matrix, which have shown great healing and biocompatibility competencies. Objectives: to obtain and characterize the properties of a decellularized biological matrix derived from the small intestine of animals. Methods: porcine small intestine was prepared and decellularized using four different methods: Triton X-100, sodium dodecyl sulfate (SDS) and sodium deoxycholate (SDC) for one or two cycles of 6 hours or 24 hours, and peracetic acid for one cycle of 2 hours. The remaining DNA was quantified with Nanodrop and electrophoresis characterization. Histology stains and Scanning Electron Microscopy (SEM) were performed to assess surface structure and integrity. Resistance assays were conducted to measure mechanical strength. Finally, degradability assays with different buffers were performed. Results: no differences between the decellularization protocols regarding remaining DNA were found, making protocols of one cycle of six hours more efficient. With the least remaining DNA content and better structure perseveration, TX-100 could be considered as the best protocol. No statistically difference between protocols and native tissue were found during the mechanical analysis. Biodegradability assays showed the expected degradability properties of the produced matrix. Conclusions: promising results were achieved to obtain decellularized biological matrices that could serve as a treatment for complicated skin wounds. More in vitro and molecular studies should be carried out in future studies to further characterize these scaffolds.

Bioceramics are significantly contributing in repairing and reconstructing the defective areas of the musculoskeletal system. Bioactive glass is a non-crystalline bioceramic that has been widely used in regeneration due to its extensive bone-forming ability and biocompatibility. The plethora of bioactive glass research has been buried over the years in the area of bone construction in various forms. The composition of the bioactive glass with its network formers and modifier plays a vital role in bone-forming ability and prevents crystallization. The hybrid polymer and metal ion-doped bioactive glass add advantages to bone tissue repair. The development and the challenge during the preparation of bioactive glasses have been discussed in this review. Based on the orthopedic defect, their porous size, volume, and even mechanical properties can be tailored to obtain the desired scaffold combined with the therapeutic delivery of bioactive compounds. Bone tissue engineering is inevitable without the process of osteoinduction, osteoconduction, and osteointegration, and their role in bioactive glass was reported. Bioactive glass is the key contributor to the glass age, and it has been subjected to medicinal applications for tissue repair, regeneration, and therapeutic agent delivery.

When manufacturing scaffolds that will be used in tissue engineering of the bone system, three properties need to be considered: (1) The biodegradation times. (2) The mechanical properties and structure of the scaffold must emulate that of the bone. (3) The biocompatibility of the scaffold with bone cells. In this work, a scaffold is obtained in the shape of a rabbit tibia using a 3D-printer with commercial polycaprolactone of medium molecular mass. Then, the scaffold is covered by electrospinning with a layer of synthesized polycaprolactone of low molecular mass. 3D-printing mimics the tissue structure in a rabbit tibia bone. Polycaprolactone is hydrophobic polymer that stops cells from adhering to the scaffold. To improve cell adhesion, gelatin molecules were grafted onto the polycaprolactone. The scaffolds were characterized with FTIR, SEM, capillary viscometry, DSC, contact angle, accelerated degradation, and DMA. The cytotoxic evaluation was carried out on scaffolds in which we used human adipose stem cells, the addition of gelatin improved cell viability. The results of the cytotoxic tests showed viability and proliferation of cells when they were seeded on the scaffolds and were evaluated on different days. Additionally, an evaluation was conducted to determine whether the scaffolds allowed for the differentiation of cells into an osteogenic lineage, when the cells were cultured with an osteoinductive medium. At 21 days, the presence of calcium nodules stained with Alizarin Red and black nodules of calcium phosphate particles stained with von Kossa was demonstrated. [ABSTRACT FROM AUTHOR]

Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp's nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary. [ABSTRACT FROM AUTHOR]

[Display omitted] • Excipients-free Astragaloside IV microfibers (SMF) was firstly reported. • SMF was injectable and has intrinsic immunoactivity. • SMF could be assembled into 3D-Scaffolds to recruit and program immune cells. • Scaffold vaccines are simply based on the mixture of SMF and tumor lysates. • SMF scaffolds boost antitumor immunity against different tumor models. Injectable scaffold tumor vaccines have emerged as an effective strategy to boost cancer immunotherapy. To minimize the reliance on expensive and diverse immunostimulatory drugs, innovative bioactive scaffolds with both biocompatibility and intrinsic immunostimulatory capabilities are highly desired. Here we demonstrate that Astragaloside IV (AS-IV), the principal bioactive component of the traditional Chinese herb Huangqi can be fabricated as mesoporous and excipients-free microfibers (SMF). SMF are injectable and can spontaneously assemble in vivo to form scaffolds with macroporous 3D structures, recruiting substantial numbers of dendritic cells (DCs) to the macropores between the packed fibers and leading to enhanced DCs maturation through an NLRP3 pathway. Without loading toxic/expensive immunostimulating drugs, AS-IV-based scaffold vaccine demonstrates impressive immunostimulatory activity and provokes efficient antitumor immunity in melanoma and breast cancer tumor models. Moreover, the resultant scaffolds can synergize well with clinically used TLR-4 agonists and immune checkpoint blockade to achieve enhanced antitumor efficacy. Materials advances in this study enable new pharmaceutical formulations as injectable bioactive scaffolds with intrinsic immunomodulating capability and suggest their great application potential in constructing safe and efficient tumor vaccines. [ABSTRACT FROM AUTHOR]

Reconsructive medicine is a growing feld for repairing damaged tissues in living organisms and is now proposed as a new treatment. For this purpose, polymeric biomaterials (scafolds) and living cells are used. The aim of this sudy was to invesigate the application of bioactive polylactic acid scafolds in the regeneration of various tissues. Polylactic acid is a synthetic biopolymer that has been proposed in recent years as an important proposal in the production of tissue engineering scafolds. This polymer is a biocompatible, biodegradable and biosorbable material that is completely hydrolyzed in the living organisms and decomposed into water and carbon dioxide molecules. Production of bioactive polylactic acid scafolds that are able to chemically bond with hos cells after in vivo implantation is a very new method in cell therapy. This method has a great impact on the process and speed of repair of various tissues such as urethral tissue, abdominal wall tissue, periodontal ligament, heart tissue, corneal tissue, bladder tissue, vascular tissue, tendon tissue, cartilage tissue, skin tissue, nerve tissue, and bone tissue. In this article, the lates and mos prominent research of clinical scientiss in the world in 2020 and 2021, in order to produce bioactive polylactic acid scafolds for regeneration of body tissues is briefy reviewed.

In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients’ motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity, low homing efficiency and cell survival rate that restrict its wider clinical applications. Evidence has shown that the positive biological effects of stem cells on tissue repair are largely mediated through paracrine action by nanostructured extracellular vesicles (EVs), which may overcome the limitations of traditional stem cell-based treatments. In addition to stem cell-derived extracellular vesicles, the potential therapeutic roles of nonstem cell-derived extracellular vesicles in critical-size bone defect repair have also attracted attention from scholars in recent years. Currently, the development of extracellular vesicles-mediated cell-free regenerative medicine is still in the preliminary stage, and the specific mechanisms remain elusive. Herein, the authors first review the research progress and possible mechanisms of extracellular vesicles combined with bone tissue engineering scaffolds to promote bone regeneration via bioactive molecules. Engineering modified extracellular vesicles is an emerging component of bone tissue engineering and its main progression and clinical applications will be discussed. Finally, future perspectives and challenges of developing extracellular vesicle-based regenerative medicine will be given. This review may provide a theoretical basis for the future development of extracellular vesicle-based biomedicine and provide clinical references for promoting the repair of critical-size bone defects.

Three-dimensional (3D) printing incorporated with controlled delivery is an effective tool for complex tissue regeneration. Here, we explored a new strategy for spatiotemporal delivery of bioactive cues by establishing a precise-controlled micro-thin coating of hydrogel carriers on 3D-printed scaffolds. We optimized the printing parameters for three hydrogel carriers, fibrin cross-linked with genipin, methacrylate hyaluronic acid, and multidomain peptides, resulting in homogenous micro-coating on desired locations in 3D printed polycaprolactone microfibers at each layer. Using the optimized multi-head printing technique, we successfully established spatial-controlled micro-thin coating of hydrogel layers containing profibrogenic small molecules (SMs), Oxotremorine M and PPBP maleate, and a chondrogenic cue, Kartogenin. The delivered SMs showed sustained releases up to 28 d and guided regional differentiation of mesenchymal stem cells, thus leading to fibrous and cartilaginous tissue matrix formation at designated scaffold regions in vitro and in vivo . Our micro-coating of hydrogel carriers may serve as an efficient approach to achieve spatiotemporal delivery of various bioactive cues through 3D printed scaffolds for engineering complex tissues., (Creative Commons Attribution license.)

The periodontium is an integrated, functional unit of multiple tissues surrounding and supporting the tooth, including but not limited to cementum (CM), periodontal ligament (PDL) and alveolar bone (AB). Periodontal tissues can be destructed by chronic periodontal disease, which can lead to tooth loss. In support of the treatment for periodontally diseased tooth, various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration (GTR) that is the current gold standard in dental clinic. Recently, various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal tissues. From a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium, technologies for scaffold fabrication have emerged in last years. This review covers the recent advancements in development of scaffolds designed for periodontal tissue regeneration and their efficacy tested in vitro and in vivo. Pros and Cons of different biomaterials and design parameters implemented for periodontal tissue regeneration are also discussed, including future perspectives.

Facilitated endogenous tissue engineering, as a facile and effective strategy, is emerging for use in bone tissue regeneration. However, the development of bioactive scaffolds with excellent osteo-inductivity to recruit endogenous stem cells homing and differentiation towards lesion areas remains an urgent problem. Chitosan (CS), with versatile qualities including good biocompatibility, biodegradability, and tunable physicochemical and biological properties is undergoing vigorously development in the field of bone repair. Based on this, the review focus on recent advances in chitosan-based scaffolds for facilitated endogenous bone regeneration. Initially, we introduced and compared the facilitated endogenous tissue engineering with traditional tissue engineering. Subsequently, the various CS-based bone repair scaffolds and their fabrication methods were briefly explored. Furthermore, the functional design of CS-based scaffolds in bone endogenous regeneration including biomolecular loading, inorganic nanomaterials hybridization, and physical stimulation was highlighted and discussed. Finally, the major challenges and further research directions of CS-based scaffolds were also elaborated. We hope that this review will provide valuable reference for further bone repair research in the future. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is involved in many critical cellular interactions through its biological macromolecules. In this study, a macroporous 3D scaffold originating from decellularized bovine liver ECM (dL-ECM), with defined compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological properties was developed. First, protocols were determined that effectively remove cells and DNA while ECM retains biological macromolecules collagen, elastin, sGAGs in tissue. Rheological analysis revealed the elastic properties of pepsin-digested dL-ECM. Then, dL-ECM hydrogel was neutralized, molded, formed into macroporous (~100–200 μm) scaffolds in aqueous medium at 37 °C, and lyophilized. The scaffolds had water retention ability, and were mechanically stable for at least 14 days in the culture medium. The findings also showed that increasing the dL-ECM concentration from 10 mg/mL to 20 mg/mL resulted in a significant increase in the mechanical strength of the scaffolds. The hemolysis test revealed high in vitro hemocompatibility of the dL-ECM scaffolds. Studies investigating the viability and proliferation status of human adipose stem cells seeded over a 2-week culture period have demonstrated the suitability of dL-ECM scaffolds as a cell substrate. Prospective studies may reveal the extent to which 3D dL-ECM sponges have the potential to create a biomimetic environment for cells. • A macroporous 3D scaffold based on decellularized bovine liver ECM was developed. • Physical, chemical, rheological and mechanical characterizations were performed. • Hemolysis test and adipose stem cell culture was carried out on scaffolds. [ABSTRACT FROM AUTHOR]

Osteochondral lesions represent a major clinical challenge, especially in the elderly. Traditional treatment strategies, such as arthroplasty or tissue engineering, have limitations and drawbacks. In this study, we presented a new treatment concept for the application of an innovative porous bioactive prosthesis with regenerative activity for the treatment of osteoarticular lesions. For regenerative activity, we fabricated chitosan/mesoporous silica nanoparticles (CS/MSNs) composite microspheres via the microfluidic method as a dual-factor carrier for the sequential release of platelet-derived growth factor BB (PDGF-BB) and kartogenin (KGN). We then integrated the factor carrier and a nondegradable polyetheretherketone (PEEK) scaffold through a surface modification technique to construct the porous sulfonated PEEK (SPK) @polydopamine (polydopamine)-CS/MSNs scaffold. We systematically evaluated the biocompatibility and biofunctionality of the SPK@PDA-CS/MSNs scaffold and implanted the scaffold in an in vivo cartilage defect model in rabbits. These results suggest that the SPK@PDA-CS/MSNs scaffold is biocompatible, promotes cell migration, enhances chondrogenic differentiation of BMSCs in vitro, and promotes cartilage regeneration in vivo. The porous bioactive prosthesis with regenerative activity presented first in this study may comprise a new therapeutic concept for osteoarticular lesions.

Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp’s nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.

Abalone shells, which contain both organic and inorganic matter, can facilitate bone remodeling and have been used to fabricate three-dimensional (3D)-printed scaffolds for bone regeneration. Herein, polycaprolactone (PCL) scaffolds were fabricated using 3D printing with abalone shell particles (ASPs) used in high-temperature processing. ASPs were heated to approximately the melting point of PCL and thermally embedded in 3D-printed PCL using a relatively simple process. The morphology and roughness of the composite scaffold changed according to the weight of ASPs used. The scaffolds were grouped as follows: ASP25 (25 mg), ASP50 (50 mg), and ASP100 (100 mg). The ASP25 group exhibited optimum cell viability and proliferation because of the direct influence of roughness and rapid pH changes. The ASP25 and ASP100 groups showed the highest alkaline phosphatase activity. This could be attributed to the effect of the alkaline environment, dissolution of calcium ions, and presence of bioactive molecules in the ASPs that could support bone regeneration. Therefore, the ASP25 group was the most suitable for fabricating bone scaffolds. This study revealed the potential applicability of ASP-embedded scaffolds in bone tissue engineering involving natural bio-organisms that self-mineralize in a process similar to human bone formation.

In this study, a novel approach has been used for the efficient synthesis of tetrahydrodipyrazolopyridine derivatives (5a–m) via a four-component one-pot condensation reaction of aromatic aldehydes, hydrazinehydrate, ethyl acetoacetate, and ammonium acetate in the presence of KCC-1-npr-NH2-DPA as an advanced nano-catalyst in ethanol under reflux conditions at 30 min. For this purpose, mesoporous fibrous nano-silica functionalized by dipenicillamine as a novel nanocatalyst (KCC-1-npr-NH2-DPA) was synthesized using a hydrothermal protocol. KCC-1-npr-NH2-DPA nano-catalyst is easily recyclable eight times without the considerable loss of catalytic activity. Other remarkable features include the short reaction time, simple work-up procedure and providing excellent yields (89–98%) of the products under mild reaction conditions. Furthermore, the effects of solvent, concentration of catalyst, time and temperature for the synthesis of tetrahydrodipyrazolopyridine (5a) were studied.

Facilitated endogenous tissue engineering, as a facile and effective strategy, is emerging for use in bone tissue regeneration. However, the development of bioactive scaffolds with excellent osteo-inductivity to recruit endogenous stem cells homing and differentiation towards lesion areas remains an urgent problem. Chitosan (CS), with versatile qualities including good biocompatibility, biodegradability, and tunable physicochemical and biological properties is undergoing vigorously development in the field of bone repair. Based on this, the review focus on recent advances in chitosan-based scaffolds for facilitated endogenous bone regeneration. Initially, we introduced and compared the facilitated endogenous tissue engineering with traditional tissue engineering. Subsequently, the various CS-based bone repair scaffolds and their fabrication methods were briefly explored. Furthermore, the functional design of CS-based scaffolds in bone endogenous regeneration including biomolecular loading, inorganic nanomaterials hybridization, and physical stimulation was highlighted and discussed. Finally, the major challenges and further research directions of CS-based scaffolds were also elaborated. We hope that this review will provide valuable reference for further bone repair research in the future.

BACKGROUND: Previous studies have shown that neurotrophin 3 (NT3)-chitosan can induce endogenous neurogenesis and axon regeneration in rats with spinal cord injury, and promote recovery of motor and sensory functions in rats. OBJECTIVE: To observe the effect of rehabilitation training combined with NT3-chitosan biomaterial scaffold on skeletal muscle morphological changes and functional recovery in rats with complete spinal cord injury. METHODS: Fifty adult female Wistar rats were randomly divided into five groups, 10 in each group. The sham group was not modeled; the remaining four groups were prepared with T7-T8 complete 5-mm spinal cord injury model, and the lesion control was not performed any intervention after modeling. The other three groups were given rehabilitation training, NT3-chitosan active biomaterial scaffold, NT3- chitosan active biomaterial scaffold combined with rehabilitation training intervention. Rehabilitation training started 2 weeks after modeling. Before operation, 2, 4, 6, 8, 10, and 12 weeks after operation, all of rats were subjected to double-blind open-field BBB scores. After 12 weeks, the skeletal muscles of the hind limbs (tibialis anterior muscle, gastrocnemius muscle, and soleus muscle) were taken for hematoxylin-eosin staining and acetylcholinesterase staining. The changes in muscle atrophy and motor endplates were assessed in each group. The experimental plan was approved by the Animal Experiment Committee of Capital Medical University (approval No. AEEI2018-105). RESULTS AND CONCLUSION: (1) The BBB score at each time point in the sham group was higher than that in the other four groups (P < 0.05); and the scores at 8, 10, and 12 weeks after the NT3-chitosan combined rehabilitation training group were higher than the lesion control group, the lesion control combined rehabilitation training group, and NT3-chitosan group (P < 0.05). (2) At 12 weeks after operation, hematoxylin-eosin staining showed that the cross-sectional area and diameter of muscle fibers of each skeletal muscle were smaller in the other four groups than that in the sham group (P < 0.05). The cross-sectional area and diameter of muscle fibers of each skeletal muscle in the NT3-chitosan combined rehabilitation training group were higher than the lesion control group, the lesion control combined rehabilitation training group, and NT3-chitosan group (P < 0.05). (3) At 12 weeks after operation, the acetylcholinesterase staining showed that the average optical density of the acetylcholinesterase on motor endplate of the muscle was lower in the other four groups than that in the sham group (P < 0.05); the average optical density of the acetylcholinesterase of the motor endplate in the NT3-chitosan combined rehabilitation training was significantly higher than that in the lesion control, lesion control combined rehabilitation training, and NT3-chitosan groups (P < 0.05). (4) The results show that NT3-chitosan combined with rehabilitation training can effectively prevent muscular atrophy of hind limb skeletal muscles in rats with complete spinal cord injury, improve the average optical density of the acetylcholinesterase of the motor endplate, reduce neuromuscular joint degeneration, and improve rat hindlimb motor function. [ABSTRACT FROM AUTHOR]

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Layer-by-layer additive manufacturing process has evolved into three-dimensional (3D) “bio-printing” as a means of constructing cell-laden functional tissue equivalents. The process typically involves the mixing of cells of interest with an appropriate hydrogel, termed as “bioink”, followed by printing and tissue maturation. An ideal bioink should have adequate mechanical, rheological, and biological features of the target tissues. However, native extracellular matrix (ECM) is made of an intricate milieu of soluble and non-soluble extracellular factors, and mimicking such a composition is challenging. To this end, here we report the formulation of a multi-component bioink composed of gelatin and alginate -based scaffolding material, as well as a platelet-rich plasma (PRP) suspension, which mimics the insoluble and soluble factors of native ECM respectively. Briefly, sodium alginate was subjected to controlled oxidation to yield alginate dialdehyde (ADA), and was mixed with gelatin and PRP in various volume ratios in the presence of borax. The formulation was systematically characterized for its gelation time, swelling, and water uptake, as well as its morphological, chemical, and rheological properties; furthermore, blood- and cytocompatibility were assessed as per ISO 10993 (International Organization for Standardization). Printability, shape fidelity, and cell-laden printing was evaluated using the RegenHU 3D Discovery bioprinter. The results indicated the successful development of ADA–gelatin–PRP based bioink for 3D bioprinting and biofabrication applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Since non-coding RNAs maintain bone homeostasis through various pathways, applications of non-coding RNAs as bioactive molecules in bone tissue engineering for bone defect repair has become an increasing area of interest. OBJECTIVE: To introduce non-coding RNAs as bioactive molecules in bone tissue engineering. METHODS: A computer-based online search of Web of Science, PubMed, SpringerLink databases was performed by the first author between December 2018 and March 2019 using the search terms "bone tissue engineering, ncRNA (miRNA, siRNA or lncRNA), scaffold, drug delivery system" to retrieve papers published during 2004-2019. A total of 1754 papers were preliminarily retrieved, and 95 of them were eligible for final analysis. RESULTS AND CONCLUSION: Because non-coding RNAs play a key role in osteogenic differentiation, they can be used as important bioactive factors for bone tissue engineering. At present, bone tissue engineering repair methods based on non-coding RNA bioactive factors have become a research hotspot in bone defect repair. There are two major application strategies: (1) The non-coding RNA transcription within the seed cells is purposefully altered and combines with the bone tissue-engineered scaffold to promote bone defect repair. (2) a specifically designed bone engineered scaffold can controllably and purposefully alter the expression of non-coding RNA in the seed cells, which promotes bone defect repair. In addition, the function of more and more non-coding RNAs has been identified in the process of bone regeneration. This shows good application prospects of non-coding RNAs. [ABSTRACT FROM AUTHOR]

The treatment of bone defects is a difficult problem in orthopedics. The excessive destruction of local bone tissue at defect sites destroys blood supply and renders bone regeneration insufficient, which further leads to delayed union or even nonunion. To solve this problem, in this study, we incorporated icariin into alginate/mineralized collagen (AMC) hydrogel and then placed the drug-loaded hydrogel into the pores of a 3D-printed porous titanium alloy (AMCI/PTi) scaffold to prepare a bioactive scaffold with the dual functions of promoting angiogenesis and bone regeneration. The experimental results showed that the ACMI/PTi scaffold had suitable mechanical properties, sustained drug release function, and excellent biocompatibility. The released icariin and mineralized collagen (MC) synergistically promoted angiogenesis and osteogenic differentiation in vitro . After implantation into a rabbit radius defect, the composite scaffold showed a satisfactory effect in promoting bone repair. Therefore, this composite dual-functional scaffold could meet the requirements of bone defect treatment and provide a promising strategy for the repair of large segmental bone defects in clinic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In this study, a novel approach has been used for the efficient synthesis of tetrahydrodipyrazolopyridine derivatives (5a–m) via a four-component one-pot condensation reaction of aromatic aldehydes, hydrazinehydrate, ethyl acetoacetate, and ammonium acetate in the presence of KCC-1-npr-NH2-DPA as an advanced nano-catalyst in ethanol under reflux conditions at 30 min. For this purpose, mesoporous fibrous nano-silica functionalized by dipenicillamine as a novel nanocatalyst (KCC-1-npr-NH2-DPA) was synthesized using a hydrothermal protocol. KCC-1-npr-NH2-DPA nano-catalyst is easily recyclable eight times without the considerable loss of catalytic activity. Other remarkable features include the short reaction time, simple work-up procedure and providing excellent yields (89–98%) of the products under mild reaction conditions. Furthermore, the effects of solvent, concentration of catalyst, time and temperature for the synthesis of tetrahydrodipyrazolopyridine (5a) were studied. [ABSTRACT FROM AUTHOR]

Abstract Bone morphogenetic protein-2 biomimetic peptide (BMPBP) is a potent osteoinductive cytokine and plays a critical role during bone regeneration. Efforts to prepare hydrogels with surface modification or physical absorption of bioactive molecules do not provide sufficient bioactivity to meet the requirements of clinical application. The goal of this study was to form a three-dimensional hydrogel comprised of BMP-2 core sequence oligopeptide, phosphoserine, a synthetic cell adhesion peptide (RGDS), and polyaspartic acid to synergistically promote osteogenesis. Experiments performed in vitro revealed that the peptide gel was conducive to adhesion and proliferation of rat marrow mesenchymal stem cells (rMSCs). In addition, RT-PCR analysis indicated that rMSCs allowed better expression of osteogenesis-related genes such as BMP-2, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Use of the rat cranial bone defects model with micro-CT 3D reconstruction showed that bone regeneration patterns occurred from one side edge toward the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore the further application potential of this bioactive scaffold. [ABSTRACT FROM AUTHOR]

Layer-by-layer additive manufacturing process has evolved into three-dimensional (3D) “bio-printing” as a means of constructing cell-laden functional tissue equivalents. The process typically involves the mixing of cells of interest with an appropriate hydrogel, termed as “bioink”, followed by printing and tissue maturation. An ideal bioink should have adequate mechanical, rheological, and biological features of the target tissues. However, native extracellular matrix (ECM) is made of an intricate milieu of soluble and non-soluble extracellular factors, and mimicking such a composition is challenging. To this end, here we report the formulation of a multi-component bioink composed of gelatin and alginate -based scaffolding material, as well as a platelet-rich plasma (PRP) suspension, which mimics the insoluble and soluble factors of native ECM respectively. Briefly, sodium alginate was subjected to controlled oxidation to yield alginate dialdehyde (ADA), and was mixed with gelatin and PRP in various volume ratios in the presence of borax. The formulation was systematically characterized for its gelation time, swelling, and water uptake, as well as its morphological, chemical, and rheological properties; furthermore, blood- and cytocompatibility were assessed as per ISO 10993 (International Organization for Standardization). Printability, shape fidelity, and cell-laden printing was evaluated using the RegenHU 3D Discovery bioprinter. The results indicated the successful development of ADA–gelatin–PRP based bioink for 3D bioprinting and biofabrication applications.

In this study, scaffolds based on chitosan/Alginate/Hardystonite (Cs/Alg/HD) were developed for bone tissue engineering (BTE). For this aim, the bioactive HD powder was synthesized and added to CS/Alg at four compositions including 0,40,55 and 70, and turned into well-ordered porous scaffolds using the direct ink writing 3D printing technique and characterized. In accordance with the results, CsAlg-HD70 demonstrated the highest yield strength (1.38 MPa) and elastic modulus (125.71 MPa), as well as the highest degradation rate and bioactivity among all compositions. The results also exhibited that the addition of HD particles had a positive effect on cell viability and attachment so that the viability of MG-63 cells exposed to the extract of the prepared scaffolds as in the case of CsAlg-HD40, reached 150% on the 7th day. Finally, the obtained results confirmed that the scaffolds prepared from CS/Alg and HD can be considered a promising alternative for BTE. [Display omitted] [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI), one of the most serious injuries of the central nervous system, causes physical functional dysfunction and even paralysis in millions of patients. As a matter of necessity, redressing the neuroleptic pathologic microenvironment to a neurotrophic microenvironment is essential in order to alleviate this dilemma and facilitate the recovery of the spinal cord. Herein, based on cell-sheet technology, two functional cell types─uninduced and neural-induced stem cells from human exfoliated deciduous teeth─were formed into a composite membrane that subsequently self-assembled to form a bioactive scaffold with a spinal-cord-like structure, called a spinal cord assembly (SCA). In a stable extracellular matrix microenvironment, SCA continuously released SCA-derived exosomes containing various neurotrophic factors, which effectively promoted neuronal regeneration, axonal extension, and angiogenesis and inhibited glial scar generation in a rat model of SCI. Neurotrophic exosomes significantly improved the pathological microenvironment and promoted in situ centralis neuroplasticity, ultimately eliciting a strong repair effect in this model. SCA therapy is a promising strategy for the effective treatment of SCI based on neurotrophic exosome delivery.

In an in-situ approach towards tissue engineered cardiovascular replacement grafts, cell-free scaffolds are implanted that engage in endogenous tissue formation. Bioactive molecules can be incorporated into such grafts to facilitate cellular recruitment. Stromal cell derived factor 1α (SDF1α) is a powerful chemoattractant of lymphocytes, monocytes and progenitor cells and plays an important role in cellular signaling and tissue repair. Short SDF1α-peptides derived from its receptor-activating domain are capable of activating the SDF1α–specific receptor CXCR4. Here, we show that SDF1α-derived peptides can be chemically modified with a supramolecular four-fold hydrogen bonding ureido-pyrimidinone (UPy) moiety, that allows for the convenient incorporation of the UPy-SDF1α-derived peptides into a UPy-modified polymer scaffold. We hypothesized that a UPy-modified material bioactivated with these UPy-SDF1α-derived peptides can retain and stimulate circulating cells in an anti-inflammatory, pro-tissue formation signaling environment. First, the early recruitment of human peripheral blood mononuclear cells to the scaffolds was analyzed in vitro in a custom-made mesofluidic device applying physiological pulsatile fluid flow. Preferential adhesion of lymphocytes with reduced expression of inflammatory factors TNFα, MCP1 and lymphocyte activation marker CD25 was found in the bioactivated scaffolds, indicating a reduction in inflammatory signaling. As a proof of concept, in-vivo implantation of the bioactivated scaffolds as rat abdominal aorta interposition grafts showed increased cellularity by CD68+ cells after 7 days. These results indicate that a completely synthetic, cell-free biomaterial can attract and stimulate specific leukocyte populations through supramolecular incorporation of short bioactive SDF1α derived peptides. [ABSTRACT FROM AUTHOR]