Bone Tissue Engineering Research Articles (Page 1)

Advances in bone tissue engineering and dental regenerative medicine have made strides in the development of several biomaterials. Optimizing the chemical and physical milieu of scaffold is required to induce osteogenesis for faster bone regeneration. In this study, polymer blend of Polyvinyl Alcohol (PVA) and Polyvinylpyrrolidone (PVP) doped with nHAP-ZnO Np was prepared by a solution casting technique. Structural and physiochemical characterization was performed. In vitro cytotoxicity analysis was performed through tetrazolium-based assay (MTT) assay and the differentiated cells were subjected to alkaline phosphatase assay (ALP) and alizarin red S (ARS) analysis respectively. Scanning Electron microscopic (SEM) analysis showed a rough and uniform matrix arrangement of the PVA-PVP blend. Crystallites properties and functional groups was confirmed by X ray diffractometer (XRD) analysis and Fourier transform infrared spectroscopy (FT-IR) respectively. The optimal water absorption capacity was observed in PVA-PVP-nHAP-ZnO Np scaffold (P3) and also degradation pattern was analysed for PVA-PVP (P1), PVA-PVP-nHAP (P2) and PVA-PVP-nHAP-ZnO Np (P3) scaffolds where P3 scaffold holds high stability compared to P1 and P2 scaffolds. In the thermal stability analysis, PVA-PVP (P1) and PVA-PVP-nHAP-ZnO Np (P3) scaffolds showed an overall stability up to 270 °C. Highly miscible blends of PVA-PVP and 1 wt% nHAP - ZnO Np was observed with semi-crystallinity in Differential Scanning Calorimetry (DSC) analysis. The mechanical property of the PVA-PVP-nHAP-ZnO Np (P3) scaffold has shown an increasing trend in tensile strength analysis. The cytotoxic study of scaffolds showed 84% of cell viability confirming high biocompatibility than compared to plain scaffold. the elevated level of ALP and calcium deposition was observed in loaded scaffold (P3). Thus, PVA-PVP-nHAP-ZnO Np (P3) scaffold supports and induces osteogenesis and can be used as biomaterial in bone regenerative medicine.

Stem cell adhesion and migration are fundamental processes in tissue regeneration and repair; however, their efficiency in vivo is often limited by the complexity of the microenvironment. Endogenous bioelectrical cues, such as electric fields present during development and wound healing, play a critical role in guiding these cellular behaviors. Piezoelectric biomaterials, which can convert mechanical stimuli into electrical signals, have recently emerged as promising platforms for recapitulating these bioelectric cues without the need for external power sources. In this mini-review, we summarize the recent advances in the use of piezoelectric scaffolds to modulate stem cell adhesion and migration. We highlight the underlying mechanisms, including integrin/focal adhesion kinase activation, calcium signaling, and electrotaxis, which mediate enhanced adhesion, focal adhesion maturation, and directed cell migration. Representative applications in bone, cartilage, nerve, and muscle tissue engineering are discussed, with an emphasis on how piezoelectric scaffolds improve regeneration by providing dynamic and self-sustained electrical stimulation. Finally, we outline the major challenges, such as balancing piezoelectric output with biocompatibility, controlling in vivo stimulation parameters, and elucidating precise sensing mechanisms, and propose future directions for clinical translation. By integrating insights from materials science, mechanobiology, and regenerative medicine, piezoelectric biomaterials hold strong potential as next-generation smart scaffolds for orchestrating stem cell behavior and accelerating functional tissue repair.

Today, the engineering of load-bearing bone tissue after severe trauma still relies on metal-based (Ti, CoCrMo alloys or stainless steel) permanent implants. Such artificial scaffolds are typically applied in the body and come into direct contact with the recipient’s cells, whose adhesion affects the patient’s implant acceptance or rejection. The present study aims to create a nano-rough texture by means of ultra-short femtosecond laser (fs)-induced periodicity in the form of laser induced periodic surface structures (LIPSS) on the surface of a stainless steel implant model, which is additionally functionalized via magnetron-sputtering with a thin Cu layer, thus providing the as-created implants with a stable antimicrobial interface. Calcium phosphate (CaP) crystal growth was additionally applied due to the strong bioactive interface bond that CaPs provide to the bone connective tissue, as well as for the strong interface bond they create between the artificial implant and the surrounding bone tissue, thereby stabilizing the implanted structure within the body. The bioactive properties in the as-created antimicrobial hybrid topographical design, achieved through femtosecond laser-induced nanoscale surface structuring and micro-sized CaP crystal growth, have the potential for subsequent practical applications in bone tissue engineering.

This study describes the green synthesis of a neodymium oxide/magnetic iron oxide (Nd2O3/Fe3O4) nanocomposite, functionalized with hydroxyapatite, using Elaeagnus angustifolia L. seeds extract. Then the effectiveness of electrospun polycaprolactone-collagen (PCL-COL) loaded with nanoparticles composites as scaffolds for bone tissue engineering was evaluated. The synthesis of nanoparticles and their elemental identification were confirmed using XRD, FT-IR, and EDX techniques. The DLS, TEM, and SEM analysis demonstrated the generation of Nd-Fe3O4@HAp NPs with an average diameter of 14-18nm. Vibrating Sample Magnetometry (VSM) validated the ferromagnetic and superparamagnetic characteristics of the nanoparticles. Tensile and contact angle analysis revealed that NP-loaded electrospun scaffolds exhibited markedly enhanced mechanical characteristics and hydrophilicity relative to pristine polymer specimens, owing to the homogeneous distribution of nanofillers throughout the polymer fibers. Additionally, cellular investigations and osteogenic potential were evaluated in vitro using adipose-derived mesenchymal stem cells (ADMSCs). Assessments of cell attachment, spreading, and proliferation of ADMSCs were conducted using SEM observation and thiazolyl blue (MTT) test. The osteogenic differentiation potential of ADMSCs on the fabricated nanofiber scaffolds was evaluated using alkaline phosphatase activity, calcium content test, and western blot analysis. ADMSCs showed better initial adherence and infiltration in nanoparticle-enhanced scaffolds compared to PCL/COL scaffolds. Additionally, our Western blot analysis demonstrated that scaffolds can effectively induce osteogenic differentiation in ADMSCs by up-regulating key proteins associated with osteogenesis (p-value < 0.0001). Thus, nanoparticle-loaded electrospun nanofibers exhibit considerable potential as effective scaffolds for applications in bone tissue engineering.

Bioceramic incorporated polymer-based scaffolds have gained more interest as a promising effective approach in bone tissue engineering (BTE) applications. This study is the first to investigate the role of incorporated manganese-doped hydroxyapatite (Mn-HA) and gelatin coating in increased bioactivity and biological properties, specifically cell attachment potencies of 3D porous electrospun polycaprolactone (PCL). In this context, the novel 3D porous composite scaffolds were synthesized by wet-electrospinning of PCL incorporated with Mn-HA. The scaffolds were then coated with a thin gelatin layer to enhance the cell adhesin capacity. The effects of Mn-HA and the gelatin coating were evaluated in terms of structural, physicochemical, and biological properties. Results have demonstrated that Mn-HA was synthesized with successfully doping of 2mol% Mn, with MnSO4 and MnCl2 precursors. Mn-HA powder with MnSO4 precursor indicated better cell viability results. Therefore, Mn-HA/PCL scaffolds having 2.5 and 5% (w/w) bioceramic content were prepared with MnSO4 precursor. The scaffolds' porosity increased from 24% (PCL/gelatin group), to approximately 34% in both 2.5 and 5% (w/w) bioceramic containing groups. The addition of Mn-HA powder improved the in vitro bioactivity and degradation rate of the scaffolds. Specifically, 5% and 2.5% (w/w) Mn-HA incorporated scaffolds indicated 40% and 30% weight loss after 21 days of incubation, respectively. In contrast to PCL/gelatin and HA containing groups, the Mn-doped HA containing scaffolds exhibited a weight loss around 17-20%, indicating a decrease in degradation. The presence of Mn-HA powder and gelatin coat elevated the cell viability results significantly, as opposed to PCL scaffolds. Incorporation of 5% (w/w) Mn-HA improved the ALP activity and intracellular calcium levels, contrary to other groups. Thus, the incorporation of Mn-doped HA and gelatin into the PCL scaffold supported the potency towards properties required for BTE applications and suggested it as a prospective biomaterial for further evaluations.

Two‐dimensional boron offers unique advantages in bone tissue engineering, unlocking capabilities that conventional additives struggle to achieve. Herein, the 2D morphology and intrinsic bioactivity of boron nanoplatelets are leveraged, to be incorporated into collagen‐based scaffolds and simultaneously achieve osteogenic, mechanically reinforcing, and antimicrobial effects, with a shift toward neurogenic, angiogenic, and anti‐inflammatory signaling. Boron nanoplatelets, synthesized from nonlayered precursors using liquid‐phase exfoliation, are combined with collagen to form boron‐collagen scaffolds (BColl). Boron significantly reinforces the collagen matrix, beneficial for mechanoresponsive bone cells. Osteoblasts and mesenchymal stem cells exhibit healthy morphology and proliferation on BColl films and scaffolds, with extended culture leading to increased alkaline phosphatase release and significantly increased calcium deposition, indicating enhanced osteogenesis. E. coli viability decreases significantly on BColl films, demonstrating their potential to limit postimplantation infections. Finally, angiogenic, neurogenic, and anti‐inflammatory signaling, with dose‐dependent upregulation of vascular endothelial growth factor‐A, nerve growth factor‐beta, and interleukin‐10, and downregulation of interleukin‐6 are observed, highlighting boron's potential to drive pro‐reparative processes. Taken together, these data showcase boron's potential for next‐generation bone biomaterials, by offering multifunctional benefits to clinically relevant aspects of bone regeneration such as mineralization, angiogenesis, and innervation, while improving the mechanical and antimicrobial properties of natural polymer scaffolds.

Firstly apatite-type carbonated calcium phosphate and biphasic calcium phosphates (mixture of phases based on Ca10(PO4)6(OH)2 and β-Ca3(PO4)2 with weight ratio 60 : 40%) which contained the trace elements complex (Na+, Mg2+, Zn2+) were obtained from aqueous solutions and heated to 600 °C. Composites based on apatite-related calcium phosphates with 5, 10, 25wt% of ZrO2 were also prepared used one-stage method. In vitro testing of new prepared samples in phosphate-buffered solution (at 37 °C and pH = 7.45) showed increasing of pH value to 10 during 96 h in the presence of apatite-related Na+ (0.6wt%), Mg2+ (0.6wt%), Zn2+ (1.7wt%), CO32- (3wt%)-containing calcium phosphate. At the same time, increasing of pH only to 8.78 during 48 h was found for the biphasic calcium phosphate with the similar amount of doping cations. This result indicates that carbonated modified hydroxyapatites can be more appropriate for bone tissue engineering than biphasic calcium phosphates with similar amount of trace elements. An increase in the ZrO2 amount from 10 to 25 wt% in the composite with apatite-related Na+ (0.6wt%), Mg2+ (0.6wt%), Zn2+ (1.7wt%), CO32- (3wt%)-containing calcium phosphate led to an increase of its hardness in 1.4 times. The results of in vitro investigation using both the MTT and resazurin assays demonstrate that the prepared apatite-related Na+ (0.6wt%), Mg2+ (0.6wt%), Zn2+ (1.7wt%), CO32-(3wt%)-containing calcium phosphate and its composite with 25 wt% ZrO2 have a dose-dependent effect on the metabolic and proliferation activity (viability) of the mouse monocyte-macrophage RAW264.7 and J774A.1 cell lines. The stimulation of RAW264.7 macrophages growth within 100–155% compared with the control was found at samples concentration 0.1 and 0.01 mg/ml in the cell cultivation medium. Obtained results are important at creation of bioactive materials with special microhardness for the medical application.

Progress in Carbon Nanotube-Assisted Osteogenic Differentiation of Mesenchymal Stem Cells and Its Application in Bone Tissue Engineering

This study investigates the characterization, and biomedical potential of Euphorbia tirucalli L. (E.tirucalli L.) extract, focusing on its bioactive compounds, antibacterial properties, and incorporation into hydroxyapatite (HA) for biomedical applications. High-Performance Liquid Chromatography (HPLC) analysis confirmed gallic acid as the predominant phenolic compound in the extract (557.9 ± 8.3 mg/g). Antibacterial testing revealed that DHA 25% exhibited the highest inhibition zones against Staphylococcus aureus (S. aureus) (7.07 ± 0.41 cm²) and Escherichia coli (E. coli) (3.14 ± 0.51 cm²), indicating enhanced antibacterial activity at higher doping concentrations. Cytotoxicity assays demonstrated that DHA 25% promoted cell proliferation (120.0 ± 5.3% on day 7), confirming its biocompatibility for bone tissue engineering. X-ray diffraction (XRD) revealed that E.tirucalli L. doping affected HA crystallinity, potentially improving bioresorption and osteoconductivity. Fourier-Transform Infrared Spectroscopy (FTIR) confirmed the successful incorporation of E.tirucalli L. into HA, while Scanning Electron Microscopy (FESEM) showed increased agglomeration and reduced porosity at higher doping concentrations. The integration of E. tirucalli L. extract into HA introduces natural bioactive compounds, such as gallic acid, that enhance antibacterial, antioxidant, and biocompatible properties beyond conventional inorganic doping approaches. In conclusion, E. tirucalli L.-doped hydroxyapatite demonstrates great potential for applications in bone regeneration and implant technology due to its enhanced antibacterial and biocompatible properties, with the possibility of future exploration for controlled drug release applications.

Potential of organ‑on‑a‑chip in advancing synthetic extracellular matrix technology for bone tissue engineering in dentistry (Review)

Since the discovery of 3D-printing, it has revolutionized personalized drug delivery and implants by enabling intricate, customizable designs. However, key challenges remain, including complex design, host immune response, biofilm formation, and infection-induced inflammation at the implant site. This work offers, first-ever, unique ginger-based 3D-printable resins by chemically modifyingZingerol (Zing-OH, a ginger-based component) into photopolymerizable compositions that can print high-resolution complex designs via DLP 3D-printing. Briefly, the Zing-OH is amended via different functional group backbones, resulting in Zing-OH-based resins (ether, ester, and urethane) and their respective prints. Moreover, the Zing-OH prints' thermal, mechanical, and biodegradation properties can be fine-tuned by simply customizing the backbone. Furthermore, the shape memory efficacy and the human bone (nasal cartilage, vestibular, cortical, femur, etc.) mimicking mechanical properties (exhibiting 2-200 MPa compressive strength) makes them more enticing. In tandem, the prints are also hemocompatible as well as cyto-friendly against human skin (HaCaT) and lung (BEAS-2B) cells, and mouse fibroblast (NIH-3T3) cells. Concurrently, an in vivo biocompatibility study in a rat model indicates that the printed materials are biocompatible, showing no signs of severe inflammatory response over a 28-day period. More importantly, the outstanding anti-biofilm and antioxidant efficacies of the Zing-OH prints make them more appealing due to their potential to prevent implant rejection, thus making them promising tools for bone-tissue engineering (BTE) applications.

Progranulin-loaded silk fibroin/chitosan scaffold with polydopamine modification promotes bone regeneration via PI3K/Akt pathway activation.

3D printing of an anatomically shaped bone model inspired by vascularized tubular bone structure.

The promising outcome of Bone Tissue Engineering (BTE) via scaffolds for treating segmental bone defects (SBDs) has led the interdisciplinary field of Materials Science to take a new turn and explore innovative biomaterials that enhance tissue regeneration. The most recent advancement is the application of electrical stimulation with the use of conductive and piezoelectric biomaterials to develop conductive and electroactive (EA) scaffolds that activate osteoblast formation, leading to a significantly faster and more robust bone healing process. Researchers have explored plenty of biomaterials and scaffold fabrication techniques. This article presents a comprehensive review of the popular biomaterials that include Conductive Polymers (PANI, Poly-pyrrole, PEDOT), Piezoelectric Polymers (PVDF, TrFE, PLLA, PAs), Metallic Nanoparticles (NPs) (Ag, TiO2), and Carbon-based NPs (CNTs, Graphene, Graphene Oxide) used for the development of conductive and EA biocompatible scaffolds. Various innovative conductive and electroactive scaffold fabricating methods, like 3D printing, bio-printing, electrospinning, etc., that precisely command over the conductive filler distribution, porosity, and pore size interconnectivity are highlighted. Tests explored by researchers for investigating the conductive and piezoelectric properties of the developed scaffolds and their osteogenic potential (in vitro and invivo) are also presented. Apart from this, standard protocols for the conduction of these tests, regulatory pathways, scope for clinical translations, and their respective challenges have been reviewed. Most importantly, the review not only focuses on the material versatility and fabrication techniques but also critically analyzes the challenges involved in optimizing the biomaterials and fabrication parameters to develop bone scaffolds with the best-optimized physicochemical, mechanical, biological, and conductive properties.

Fabrication, physicochemical characterization and in vitro evaluation of pre-osteoblast cells on bacterial cellulose/hydroxyapatite reinforced with chitosan composite scaffold for bone tissue engineering.

3D - pored Ixora Coccinea Linn. extracted nanocellulose-curcumin composites for tissue engineering applications.

Ginger extract release from 3D printed calcium phosphate scaffolds for bone tissue engineering

In this study, calcium aminopolycarboxylate-based coordination polymers, calcium acetamidoiminodiacetate (CaADA) and tetraaqua(ethylenediaminetetraacetato)-calcium (II) strontium (II) monohydrate (SrCaEDTA) were incorporated into polyacrylamide-sodium alginate hydrogel scaffolds, aiming to improve calcium absorption in MG-63 cells. Cytotoxicity of the coordination polymers in MG-63 osteoblast-like cells was studied by MTT assay. The mechanical performance and degradation behaviour of the scaffolds were systematically investigated. Porosity measurements were done via SEM analysis, and calcium ion release profile was evaluated by inductively coupled plasma mass spectrometry (ICP-MS) measurements. The calcium deposition studies revealed that the integration of the coordination polymers enhanced the calcium absorption in MG-63 cells. The coordination polymer-incorporated hydrogel scaffolds can be developed as future materials for bone tissue engineering and bone repair applications.

Whitlockite as a next-generation biomaterial for bone regeneration: A systematic review of In Vivo evidence for bone regeneration.

Harmonizing dual electrospun/sponge structures within a triad gellan gum/eucalyptus/Cu-doped baghdadite composition for bone tissue engineering