Biomaterials For Bone Regeneration Research Articles

Alginate-HEMA Hydrogels as Promising Biomaterials for Bone Regeneration: InVitro and InVivo Studies.

In the present work, the osteogenic and angiogenic properties of, previously developed, semi-interpenetrated HEMA-EGDMA polymeric networks (sIPN) with and without alginate with application in bone tissue engineering (BTE) were studied. Invitro characterization studies were performed using rat bone marrow progenitor cells (BMPCs), EA.hy926 endothelial cells, and rat vascular smooth muscle cells (VSMCs). Based on the invitro results of both this work and previous ones, the hydrogels were selected to carry out invivo studies to find out their capacity as a biomaterial using a bone regeneration model. Our results indicate that the incorporation of alginate into the HEMA-EGDMA polymeric network promotes osteogenic and angiogenic capacity in cell cultures of BMPCs and both EA.hy926 and VSMCs, respectively, and also increases bone formation and vascular structures in invivo studies, demonstrating its potential use as a biomaterial in BTE.

The Deposition of Hydroxyapatite Particles Within an Organic Matrix on the Surface of Poly(lactic acid)

Hydroxyapatite (HAP) is a well-established material in biomedical applications, especially for bone tissue regeneration, dental implants, and drug delivery systems. Recent research emphasizes enhancing the biocompatibility and osteoconductivity of orthopedic implants using HAP. This study explores the potential of combining HAP with a lipid matrix to improve the surface properties and biocompatibility of poly(lactic acid) (PLA)-based, 3D-printed, resorbable bone implants. We utilized the Langmuir–Blodgett method to deposit HAP within a dihexadecyl phosphate (DHP) matrix onto PLA substrates. This study demonstrates that DHP and HAP form stable monolayers at the air/water interface with HAP particles distributed within a homogeneous lipid matrix. The presence of HAP and the resulting changes in surface free energy (SFE) are hypothesized to enhance the biocompatibility of PLA implants. Our findings indicate that films composed of DHP + HAP 5:1 are particularly effective in altering PLA surface characteristics, potentially improving osteointegration, and reducing microbial adherence. Overall, this work highlights that surface modification of PLA with HAP and lipid matrices is the first step towards new, promising, and cost-effective strategies for developing advanced biomaterials for bone regeneration.

Potential of Cranberry to Stimulate Osteogenesis: An In Vitro Study

This study investigated the potential of Cranberry extract to stimulate osteogenesis in vitro. The total phenolic and monomeric anthocyanin contents in the Cranberry were determined. Liquid chromatography coupled with mass spectrometry was used to identify the Cranberry’s constituents. To assess the Cranberry’s cytotoxicity, a thiazolyl blue tetrazolium bromide assay was employed. Concerning the osteogenesis potential of Cranberry, alkaline phosphatase (ALP) activity, bone morphogenetic protein 2 (BMP-2) expression, and extracellular matrix mineralization were evaluated. The total phenolic content was 522.72 ± 9.80 mg GAE g-1 ES and 364.95 ± 12.49 mg GAE/g detected by the Fast Blue BB and Folin–Ciocalteu method, respectively. For monomeric anthocyanin, the content was 460 ± 30 mg ECG g-1 ES. Moreover, Cranberry concentrations ranged from 62.5 to 500 mg/mL and were found to be biocompatible with osteoblasts and mesenchymal stromal cells. Regarding osteogenesis, 20 mg/mL of Cranberry promoted 2-fold more ALP activity and almost 1.5-fold more BMP-2 than compared to the positive control group. Additionally, 200 mg/mL of Cranberry stimulated a 1.7-fold increase in extracellular matrix mineralization compared to the positive control group. In conclusion, Cranberry displayed potential in stimulating early and late markers of osteogenesis. Its ability to promote osteogenesis and its biocompatibility at higher concentrations hold promise for future application into biomaterials for bone regeneration.

Autogenous Tooth Graft Biomaterial in Guided Bone Regeneration: A Comprehensive Review

Objective: This review evaluated the use of autogenous tooth as a bone graft material in guided bone regeneration (GBR). Moreover, it compared the results of GBR using autogenous demineralized dentin, partially demineralized dentin, and mineralized dentin with or without membrane to verify its clinical advantage, effectiveness, and safety. Methods: A search was conducted in PubMed/MEDLINE, Lilacs, Embase, Cochrane, and Scopus databases. Specific criteria were established for the inclusion and exclusion of studies, including types of studies considered, target population (clinical studies: humans), evaluated intervention (studies assessing and comparing autologous demineralized dentin, partially demineralized dentin, and mineralized dentin in GBR with or without resorbable membrane), and language and publication period of articles (English and published in the last 11 years). A detailed assessment of the methodological quality of the selected studies was conducted using the JBI critical appraisal tool. Results: Based on the analysis conducted, out of 174 potentially relevant articles obtained, only 19 publications met the inclusion criteria, with three papers showing medium quality/moderate risk of bias and the rest with high quality/low risk of bias. Comparison between groups revealed stability of the newly formed bone, low marginal bone loss, clinically acceptable primary and secondary implant stability quotient (ISQ) values, and high implant survival rates after using autogenous tooth biomaterial. Conclusions: The results of this review on the use of autogenous teeth as a bone graft material in guided bone regeneration indicated that the technique has the potential to be an effective and safe treatment option. Analysis of selected studies showed favorable evidence for the use of autogenous teeth in bone regeneration, suggesting clinical benefits, most for socket preservation. These results are relevant for guiding clinical practice and assisting dental professionals in having options for biomaterials for bone regeneration.

Research progress of gene therapy combined with tissue engineering to promote bone regeneration

Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is a common clinical need. Meanwhile, many preclinical data have demonstrated that gene and cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, and molecules with stimulatory capability, provides promising alternatives to enhance bone regeneration. To deliver and localize growth factors and associated intracellular signaling components into the defect site, gene therapy strategies combined with bioengineering could achieve a uniform distribution and sustained release to ensure mesenchymal stem cell osteogenesis. In this review, we will describe the process and cell molecular changes during normal fracture healing, followed by the advantages and disadvantages of various gene therapy vectors combined with bone tissue engineering. The growth factors and other bioactive peptides in bone regeneration will be particularly discussed. Finally, gene-activated biomaterials for bone regeneration will be illustrated through a description of characteristics and synthetic methods.

Tailoring surface stiffness to modulate senescent macrophage immunomodulation: Implications for osteo-/angio-genesis in aged bone regeneration

The application of biomaterials in bone regeneration is a prevalent clinical practice. However, its efficacy in elderly patients remains suboptimal, necessitating further advancements. While biomaterial properties are known to orchestrate macrophage (MΦ) polarization and local immune responses, the role of biomaterial cues, specifically stiffness, in directing the senescent macrophage (S-MΦ) is still poorly understood. This study aimed to elucidate the role of substrate stiffness in modulating the immunomodulatory properties of S-MΦ and their role in osteo-immunomodulation. Our results demonstrated that employing collagen-coated polyacrylamide hydrogels with varying stiffness values (18, 76, and 295 kPa) as model materials, the high-stiffness hydrogel (295 kPa) steered S-MΦs towards a pro-inflammatory M1 phenotype, while hydrogels with lower stiffness (18 and 76 kPa) promoted an anti-inflammatory M2 phenotype. The immune microenvironment created by S-MΦs promoted the bioactivities of senescent endothelial cells (S-ECs) and senescent bone marrow mesenchymal stem cells BMSCs (S-BMSCs). Furthermore, the M2 S-MΦs, particularly incubated on the 76 kPa hydrogel matrices, significantly enhanced the ability of angiogenesis of S-ECs and osteogenic differentiation of S-BMSCs, which are crucial and interrelated processes in bone healing. This modulation aided in reducing the accumulation of reactive oxygen species in S-ECs and S-BMSCs, thereby significantly contributing to the repair and regeneration of aged bone tissue.

Macrophage-Centric Biomaterials for Bone Regeneration in Diabetes Mellitus: Contemporary Advancements, Challenges, and Future Trajectories.

Increased susceptibility to bone fragility and the diminution of bone regenerative capacity are recognized as significant and frequent sequelae of diabetes mellitus. Research has elucidated the pivotal role of macrophages in the pathogenesis and repair of diabetic bone defects. Notwithstanding this, the therapeutic efficacy of traditional interventions remains predominantly inadequate. Concomitant with substantial advancements in tissue engineering in recent epochs, there has been an escalation in the development of biomaterials designed to modulate macrophage activity, thereby augmenting osseous tissue regeneration in the context of hyperglycemia. This review amalgamates insights from extant research and delineates recent progressions in the domain of biomaterials that target macrophages for the regeneration of diabetic bone, whilst also addressing the clinical challenges and envisaging future directions within this field.

Unlocking the potential of stimuli-responsive biomaterials for bone regeneration.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

Peripheral sensory nerve regeneration: Novel target in bone tissue engineering

AbstractSynthetic biomaterials are emerging candidate solutions for treating large bone defects. However, the clinical performances of most synthetic materials are not satisfactory, with the need for improvement in design and synthesis. Although bone is highly innervated, the central role during healing of the peripheral nervous system, and in particular sensory nerves (SNs), has only recently been acknowledged. SNs can improve osteogenic differentiation of bone marrow stem/stromal cells through neurotransmitters and peptides; the interplay between SNs and the vascular system also facilitates vascular network reconstruction, indirectly facilitating bone healing. These factors suggest the importance of SNs in bone healing, a vital point that has been overlooked in bone biomaterial design until very recently. SN regeneration represents a novel direction in the development of biomaterials for bone regeneration. The current perspective paper summarizes the cellular and molecular mechanisms under the regulatory influence of SNs in the bone healing process and outlines the recent advances in biomaterials for innervated bone tissue regeneration. This establishes potential future directions for bone engineering biomaterial design.

Silver and silicon doped βTCP scaffolds with gentamicin or ceftazidime loaded P(3HB) coatings as multifunctional biomaterials for bone regeneration

The risk of bacterial infections is a significant challenge faced frequently in the use of implants or scaffolds for bone regeneration. Therefore, this study focusses on the development and characterisation of novel β tricalcium phosphate (βTCP) scaffolds co-doped with silver and silicon, along with composites coated with antibiotic-loaded poly(3-hydroxybutyrate) (P(3HB)) layers. The successful incorporation of silver and silicon dopants while maintaining the formation of βTCP phase was confirmed using X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) analysis. The developed materials demonstrated comparable total and open porosity (∼64–70 vol%), suggesting high interconnectivity between pores conducive to nutrient transport and tissue repair. The increase in compressive strength was achieved for both doped (4.73 ± 0.79 MPa) and P(3HB) coated (5.79 ± 0.92 MPa) scaffolds due to the fine bioceramic microstructure and polymeric coating. Silver and silicon-modified βTCP demonstrated enhanced growth inhibition of Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains in vitro compared to the pure βTCP. P(3HB) coatings, enriched with gentamicin or ceftazidime, exhibited burst and sustained release of the antibiotics from the scaffolds up to 120 h further intensifying the bacteria-killing capability, with evident inhibition zones observed in vitro. Moreover, the composites exhibited apatite-forming ability, suggesting their bioactive potential. In vivo evaluation using Caenorhabditis elegans demonstrated the lack of toxicity of the tested materials. The simultaneous incorporation of the dopants and antibiotic-loaded P(3HB) coatings not only offer a dual antibacterial approach but may also facilitate bone regeneration. However, further in vitro and in vivo investigations are needed to assess their potential in clinical application.

Bone Tissue Engineering and Nanotechnology: A Promising Combination for Bone Regeneration.

Large bone defects are the leading contributor to disability worldwide, affecting approximately 1.71 billion people. Conventional bone graft treatments show several disadvantages that negatively impact their therapeutic outcomes and limit their clinical practice. Therefore, much effort has been made to devise new and more effective approaches. In this context, bone tissue engineering (BTE), involving the use of biomaterials which are able to mimic the natural architecture of bone, has emerged as a key strategy for the regeneration of large defects. However, although different types of biomaterials for bone regeneration have been developed and investigated, to date, none of them has been able to completely fulfill the requirements of an ideal implantable material. In this context, in recent years, the field of nanotechnology and the application of nanomaterials to regenerative medicine have gained significant attention from researchers. Nanotechnology has revolutionized the BTE field due to the possibility of generating nanoengineered particles that are able to overcome the current limitations in regenerative strategies, including reduced cell proliferation and differentiation, the inadequate mechanical strength of biomaterials, and poor production of extrinsic factors which are necessary for efficient osteogenesis. In this review, we report on the latest in vitro and in vivo studies on the impact of nanotechnology in the field of BTE, focusing on the effects of nanoparticles on the properties of cells and the use of biomaterials for bone regeneration.

Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7/PI3K/Akt signaling pathway

Although calcium‑magnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.

Multiple biomaterials for immediate implant placement tissue repair: Current status and future perspectives

AbstractImmediate oral implant placement is a widely accepted technique, known for its efficacy in reducing treatment duration, surgical visits, and overall healing time. One of the primary challenges associated with immediate implant placement is the attainment of initial stability. The inevitable loss of bone and soft tissue after extraction poses a risk to implant osseointegration in both vertical and horizontal dimensions. Guided tissue regeneration/guided bone regeneration (GTR/GBR) is a well‐established method for periodontal regeneration. However, current GTR/GBR membranes lack tissue inherent regeneration properties and necessitate combination with grafts to enhance tissue recovery. In this context, biomaterials have emerged as a promising option due to their good biocompatibility, biodegradability, and bioactive properties. They present a potential alternative to standard autologous/allograft procedures. The field of biomaterials for bone regeneration has rapidly evolved, developing new guiding materials and engineering techniques. These advances have become integral in addressing tissue defects at the immediate implant site. Various materials such as bioceramics, natural polymers, and synthetic polymers have been used for tissue repair. This article undertakes an etiological examination of tissue deficiency associated with immediate implant placement. Additionally, it reviews the advantages and disadvantages of a variety of biomaterials, aiming to provide references for clinical treatment and areas for further investigation.

In vivo assessment of marine vs bovine origin collagen-based composite scaffolds promoting bone regeneration in a New Zealand rabbit model

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic.The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.

Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration.

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nanovehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymers. The review covers some of the properties of PLGA, with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs and PLGA-based products available on the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases.

Bmp-2 Gene-Transferred Skeletal Muscles with Needle-Type Electrodes as Efficient and Reliable Biomaterials for Bone Regeneration.

Bone morphogenetic protein-2 (bmp-2) has a high potential to induce bone tissue formation in skeletal muscles. We developed a bone induction system in skeletal muscles using the bmp-2 gene through in vivo electroporation. Natural bone tissues with skeletal muscles can be considered potential candidates for biomaterials. However, our previous system using plate-type electrodes did not achieve a 100% success rate in inducing bone tissues in skeletal muscles. In this study, we aimed to enhance the efficiency of bone tissue formation in skeletal muscles by using a non-viral bmp-2 gene expression plasmid vector (pCAGGS-bmp-2) and needle-type electrodes. We injected the bmp-2 gene with pCAGGS-bmp-2 into the skeletal muscles of rats' legs and immediately placed needle-type electrodes there. Skeletal tissues were then observed on the 21st day after gene transfer using soft X-ray and histological analyses. The use of needle-type electrodes resulted in a 100% success rate in inducing bone tissues in skeletal muscles. In contrast, the plate-type electrodes only exhibited a 33% success rate. Thus, needle-type electrodes can be more efficient and reliable for transferring the bmp-2 gene to skeletal muscles, making them potential biomaterials for repairing bone defects.

Consolidation of Spray-Dried Amorphous Calcium Phosphate by Ultrafast Compression: Chemical and Structural Overview.

A large amount of research in orthopedic and maxillofacial domains is dedicated to the development of bioactive 3D scaffolds. This includes the search for highly resorbable compounds, capable of triggering cell activity and favoring bone regeneration. Considering the phosphocalcic nature of bone mineral, these aims can be achieved by the choice of amorphous calcium phosphates (ACPs). Because of their metastable property, these compounds are however to-date seldom used in bulk form. In this work, we used a non-conventional "cold sintering" approach based on ultrafast low-pressure RT compaction to successfully consolidate ACP pellets while preserving their amorphous nature (XRD). Complementary spectroscopic analyses (FTIR, Raman, solid-state NMR) and thermal analyses showed that the starting powder underwent slight physicochemical modifications, with a partial loss of water and local change in the HPO42- ion environment. The creation of an open porous structure, which is especially adapted for non-load bearing bone defects, was also observed. Moreover, the pellets obtained exhibited sufficient mechanical resistance allowing for manipulation, surgical placement and eventual cutting/reshaping in the operation room. Three-dimensional porous scaffolds of cold-sintered reactive ACP, fabricated through this low-energy, ultrafast consolidation process, show promise toward the development of highly bioactive and tailorable biomaterials for bone regeneration, also permitting combinations with various thermosensitive drugs.

Effects of void defects on the mechanical properties of biphasic calcium phosphate nanoparticles: A molecular dynamics investigation

Porous biphasic calcium phosphate (BCP) ceramics are widely used in bone tissue engineering, and the mechanical properties of BCP implants must be reliable. However, the effects of pore structure (e.g., shape and size) on the mechanical properties are not well understood. In this study, we used molecular dynamics simulations to investigate the influence of pore shape and size on the mechanical behavior of BCP nanoparticles. BCP void models with cylindrical and cuboid pores ranging from 2 to 16 nm in diameter were constructed, and the elastic moduli were calculated. In addition, uniaxial tensile and compressive tests were performed on the models. We found that the pore size had a more significant impact on the mechanical properties of BCP than pore shape. Further, the elastic moduli decreased nonlinearly with increasing pore size. In addition, the tensile and compressive strength also decreased with the increase in pore size, but the ductility improved. Furthermore, deformation and fracture were more likely to occur near the pores and at the phase interfaces as a result of high atomic local strain in the calcium-deficient hydroxyapatite area. The results of this work reveal the effects of pore parameters on the mechanical properties of porous BCP at the nanometer level, which may aid the design of improved porous and multiphase CaP-based biomaterials for bone regeneration.

Integrating hydroxyapatite and bovine bone mineral into cellulose–collagen matrices for enhanced osteogenesis

Advanced biomaterials for bone regeneration, combining cellulose/aminomethylphenylboronic cellulose, collagen, and hydroxyapatite or InterOss® to enhance structural support and prevent infections.

TEM Analysis and Insights into the Physicomechanical Characteristics of CeLa-Substituted Bio-Glass Ceramics

Among rare earth metals, bio-glass ceramics have gained significant attention for their potential applications in bone tissue engineering and regenerative medicine due to their biocompatibility and bioactivity. This research paper investigates the physico-mechanical properties of CeLa-substituted bio-glass ceramics using Transmission Electron Microscopy (TEM) analysis. The study aims to elucidate the microstructural features, crystalline phases, and mechanical behavior of CeLasubstituted bio-glass ceramics, providing valuable insights into their suitability for biomedical applications. The TEM analysis reveals intricate details of the material’s nanostructure, highlighting the influence of CeLa substitution on phase composition, grain morphology, and mechanical performance. The findings contribute to a better understanding of the structure-property relationships in CeLa-substituted bio-glass ceramics, guiding the development of advanced biomaterials for bone regeneration and tissue repair.