Hydroxyfluorapatite (HFAp) materials possess a structural and compositional similarity to bone tissue and dentin. These bioceramics facilitate various physiological functions, including ion exchange within surface layers. Additionally, magnesium (Mg) serves as a primary substitute for calcium in the biological apatite found in the calcified tissues of mammals, while zinc (Zn) contributes to overall bone quality and exhibits antibacterial properties. Although multiple studies have examined the individual substitution of ions within the hydroxyapatite (HAp) structure, no research to date has investigated the simultaneous substitution of zinc, fluoride, and varying amounts of magnesium in calcium HAp. This study explores the incorporation of magnesium into the structure of zinc-calcium hydroxylfluorapatite. A series of ion-substituted apatites, represented as Ca9.9-xZn0.1Mgx (PO4)6(OH)F with 0 ≤ x ≤ 1, were synthesized. Characterization of the produced samples confirmed that they were monophase apatite, crystallizing in the hexagonal P63/m space group, with only a slight impact on crystallinity due to magnesium doping. Pressure-less sintering of the samples demonstrated that maximum densification, approximately 94%, was achieved at 1200 °C with a sintering dwell of 1 h for the sample with x = 0.1. Furthermore, the Young's and Vickers hardness of this sample reached peak values of 105 and 5.02 GPa, respectively. When immersed in simulated body fluid, the formation of an amorphous CaP which can subsequently be crystallized into crystalline phase on the surface of dense specimens was observed, indicating the ability to bond with bone in a living organism and their potential use as substitutes for failed bone and dentin filling and coating.

Biomineralization has garnered profuse attention in multidisciplinary fields. Using this strategy, living things, including eukaryotes or prokaryotes, mediate the uptake of ions from the surrounding environment, followed by assembling and depositing them as greatly configured structures inside the organic matrix. The generated biominerals, including nanomaterials, possess outstanding hierarchical structures that exceed their chemically synthesized counterparts. Despite the significant progress achieved in microbial-mediated mineralization, several key knowledge gaps remain, including mechanisms controlling biomineralization pathways and the impact of environmental factors on mineral morphology, crystallinity, and stability. This review provides a comprehensive description of this biomineralization, which can be categorized into controlled, influenced, and induced biomineralization. Interestingly, we highlighted biologically-induced mineralization approaches, such as photosynthesis, methane oxidation, and nitrogen-based metabolic pathways, and identified various chemical interactions during mineral production following analytical chemistry. This review also extensively delineates updates on application of biominerals across all fields, commencing with the remediation of deleterious pollutants and biominerals exploited in industrial sectors, moving on to using them to reinforce soil, generate biocement for construction, and delving into their utilization in pharmaceutical applications to deliver drugs, repair teeth and bones, and combat cancer and pathogenic microorganisms. Moreover, the review outlines the drawbacks and adequate solutions for biomineralization, particularly CaCO₃-mediated processes, such as the generation of ammonium and nitrate during the CaCO₃ precipitation process and the relatively slow rate of microbial-mediated mineralization. Biomineralization inspired the fabrication of smart biomaterials, which combine biological advantages. Overall, this comprehensive review discusses updated research and highlights potential approaches to future studies.

The development of composite hydrogels with enhanced biocompatibility and osteoconductivity remains a critical focus in bone tissue engineering. In this study, we designed a double-network hydrogel composed of chitosan, and gelatin (CG), crosslinked to improve its mechanical properties for bone regeneration applications. To further enhance its bioactivity, zinc oxide nanoparticles (ZnO) were incorporated into the hydrogel matrix. Prior to incorporation, ZnO was functionalized with a mussel-inspired polydopamine (PDA) coating, forming ZnO/PDA. Subsequently, in situ mineralization facilitated the deposition of calcium and phosphate (CaP) ions, yielding ZnO/PDA/CaP (m-ZnO). To evaluate the effects of these modifications, three hydrogel formulations were prepared: pure CG hydrogel, CG hydrogel containing ZnO/PDA (CG@Z/P), and CG hydrogel incorporated with m-ZnO (CG@m-ZnO). The addition of m-ZnO significantly enhanced the compressive strength of CG@m-ZnO, increasing it from 335.05 ± 8.35 kPa to 973.31 ± 102.19 kPa, while maintaining microstructural integrity. The incorporation of ZnO also imparted antibacterial properties, whereas the PDA and CaP layers promoted cell adhesion and proliferation. Notably, CG@m-ZnO with 50 μg/mL of m-ZnO exhibited excellent biocompatibility and significantly enhanced osteogenic differentiation of MC3T3-E1 cells, as evidenced by increased alkaline phosphate (ALP) activity and Alizarin Red S (ARS) staining. In conclusion, the CG@m-ZnO hydrogel demonstrates a synergistic combination of biocompatibility, osteoconductivity, antibacterial activity, and enhanced mechanical properties, making it a promising candidate for bone tissue engineering and regenerative medicine applications.

Phosphate conversion coatings on metallic implants can synergistically integrate functional components and structural regulation, offering excellent biocompatibility and osteogenic activity. However, the passive oxide layer on the titanium (Ti) surface impedes the following chemical reactivity, adversely affecting the microstructure and properties of phosphate coatings. This study proposes a strategy for achieving structural optimization and properties enhancement of strontium-zinc phosphate (SrZnP) conversion coatings on Ti via regulating interface chemical reaction between coatings and Ti substrates. The results indicated that Sr2+ and Zn2+ ions-preloading (IPL) treatment enhanced the interfacial reactivity, which can further achieve crystal refinement and uniform crystal size in nucleation. In contrast, microstructural modifications on Ti substrates induced by acid etching, sandblasting, and alkali etching had minimal effects on the phase composition and crystal morphology (irregular cubic) of the SrZnP coatings. The coatings on IPL-Ti exhibited better mechanical properties and corrosion resistance. Besides, the coatings with optimized structures and surface characteristics elicited bacterial growth inhibition rates of 91.09% and 84.04% against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. Meanwhile, the crystal-refined coatings further significantly enhanced the adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells (BMSCs), proving anticipated osteogenic activity. Overall, the ions preloading strategy on variable micro/nanostructured Ti substrates facilitates the potential application of Sr/Zn-phosphate conversion coatings for repairing infected bone defects.

Recognizing the complexity of the bone regeneration cascade and understanding the adverse effects of using growth factors, it is crucial to develop a growth factor-free scaffold with multiple functions to modulate various aspects of the regenerative process. This study explores a novel macroporous multifunctional bone graft for bone regeneration, aiming to overcome complications associated with current treatment modalities. The study reveals enhanced bone regeneration and vascularization by integrating silica hybrid and nano-whitlockite (nWH) into cryogel-based composite scaffolds. The physicochemical properties, in vitro angiogenic and osteogenic potential, three-dimensional (3D) vasculogenesis, osteoclastogenesis, and proinflammatory responses of the composite cryogels were systematically examined. Results showed augmented effects for nWH-containing silica hybrid cryogels, particularly notable in the 1:0.5 WH2.5 group. Cryogels promoted angio- and vasculogenesis, and osteogenic differentiation while reducing osteoclast formation and proinflammatory responses in vitro. Optimal composition analysis consistently favored the 1:0.5 WH2.5 group. Implantation in a critical-sized cranial defect model in mice demonstrated enhanced vascularization and new bone formation. Thus, this study demonstrates the synergistic effect of silica hybrid and nWH in critical-sized bone defects.

Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) is the major inorganic component of bones, with high bioactivity and biocompatibility, and pores in the 50-200 μm range can facilitate cell anchorage and proliferation. HAp was synthesised through a rapid sol-gel method, avoiding the usual long aging process typically required for sol-gel HAp. Acetate and nitrate precursor salts were compared, to produce bioceramics having different porosities induced via the addition of hydrogen peroxide (H2O2) pore-forming agent. 3-10 wt% H2O2 was added, and the resulting bioceramics calcined at 400 and 700 °C. Microstructure, composition, specific surface area and macro/mesoporosity were analysed, and bioactivity and cytotoxicity/biocompatibility evaluated by immersion in simulated body fluid (SBF) and MTT assays on MG63 osteoblast cell lines. When heated to 400 °C HAp was the only calcium phosphate phase present, but after heating to 700 °C they were a mixture of HAp and β-tricalcium phosphate (β-TCP, Ca3(PO4)2). The bioceramics exhibit high bioactivity, crystallising HAp from SBF, and most were biocompatible, with cell viabilities of 110-139% for samples with 3 wt% H2O2 derived from nitrates, or from acetates heated to 700 °C. This is the first time that HAp-based bioceramics derived from a rapid sol-gel process have been produced with such induced porosity.

This study presents the development of an innovative injectable bioactive material, BG-ETa, for bone regeneration. Porcine-derived dermal extracellular matrix (dECM) was decellularized and combined with beta-tri calcium phosphate (β-TCP) and porous bio-glass (BG) beads, followed by freeze-drying to produce surface-modified BG beads. Incorporating sodium alginate (SA) enhanced injectability of the system, enabling effective delivery to defect sites. Bio-glass promotes osteogenic support and osteogenesis. dECM, rich in essential proteins and growth factors, mimics the bone microenvironment to improve cell adhesion, proliferation, and differentiation. The bioactive dECM/β-TCP coating on the bead surface offers neovascularization and early mineralization properties which ultimately facilitates new bone formation. In vitro assays demonstrated BG-ETa's biocompatibility, antimicrobial properties, and potential for osteogenic differentiation, with significant results in alkaline phosphatase (ALP) activity, alizarin red staining (ARS), immunocytochemistry (ICC), and gene expression through real-time PCR. In vivo implantation in rabbit femoral defects revealed promising degradation and significant bone regeneration after 4 and 8 weeks, as observed by histological analysis and micro-CT imaging. This injectable BG-ETa system holds promise as an effective alternative to traditional grafts, providing bioactive environment for enhanced bone regeneration with the potential to overcome limitations associated with autologous or allogeneic grafting.

Fabrication of macroporous scaffolds with favorable mechanical and biological properties based on natural polysaccharides embedding inorganic components has emerged as a promising alternative for bone regeneration. We hypothesized that partially demineralized chitin containing natural calcium phosphate with suitable mechanical strength as the inorganic component is more favorable for this purpose than commonly used nano-hydroxyapatite (nHA). Therefore, a macroporous cryogel scaffold composed of gelatin (G), nanofibrillated cellulose (NFC), and partially demineralized chitin (PDCh), chemically crosslinked with oxidized dextran (ODex), was developed in this study. The scaffold exhibited suitable aqueous solvent absorption, with a controlled degradation and proper calcium phosphate concentration and a 50-500 μm pore size distribution that promoted cell growth and osteogenesis. Incorporating PDCh provided a high surface-to-volume ratio and significantly enhanced the scaffold's mechanical properties with a compressive strength of 315.4 kPa, suitable for cancellous bone regeneration. Moreover, the presence of natural calcium phosphate in PDCh led to superior biocompatibility and bone differentiation in human mesenchymal stem cells (hMSCs), as evidenced by an increase in calcium deposition, higher alkaline phosphatase (ALP) activity, and an increase in collagen-type 1 and osteocalcin gene expression compared to scaffold containing nHA. These results demonstrated the promising potential of gelatin/nanofibrillated cellulose/PDCh cryogel scaffolds for bone tissue engineering applications.

Large bone defects in load-bearing bone can result from tumor resection, osteomyelitis, trauma, and other factors. Although bone has the intrinsic potential to self-repair and regenerate, the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge. Traditionally, repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites, and autogenous bone grafting remains the "gold standard" treatment. However, the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone, donor-site morbidities, and the risk of rejection. In recent years, the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes. In addition to osteoconductivity and osteoinductivity, optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects, but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength. A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements. In this review, the use of traditional bone grafts in load-bearing bone defects, as well as their advantages and disadvantages, is summarized and reviewed. Furthermore, we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance, structural, and functional bionics to provide ideas and directions for future research.

Bone defects caused by various traumas and diseases such as osteoporosis, which affects bone density, and osteosarcoma, which affects the integrity of bone structure, are now well known. Given this situation, several innovative research projects have been reported to improve orthopedic methods and technologies that positively contribute to the regeneration of affected bone tissue, representing a significant advance in regenerative medicine. This review article comprehensively analyzes the transition from existing methods and technologies for implants and bone tissue regeneration to innovative biomaterials. These biomaterials have been of great interest in the last decade due to their physicochemical characteristics, which allow them to overcome the most common limitations of traditional grafting methods, such as the availability of biomaterials and the risk of rejection after their application in regenerative medicine. This could be achieved through an exhaustive study of the applications and properties of various materials with potential applications in regenerative medicine, such as using magnetic nanoparticles and hydrogels sensitive to external stimuli, including pH and temperature. In this regard, this review article describes the most relevant compounds used in bone tissue regeneration, promoting the integration of these biomaterials with the affected area's bone structure, thereby allowing for regeneration and preventing amputation. Additionally, the types of interactions between biomaterials and mesenchymal stem cells and their effects on bone tissue are discussed, which is critical for developing biomaterials with optimal regenerative properties. Furthermore, the mechanisms of action of the various biomaterials that enhance osteoconduction and osteoinduction, ensuring the success of orthopedic therapies, are analyzed. This enables the treatment of bone defects tailored to each patient's condition, thereby avoiding limb amputation. Consequently, a promising future for regenerative medicine is emerging, with various therapies that could revolutionize the management of bone defects, offering more efficient and safer solutions.

Titanium (Ti) implants are widely used for tooth replacement due to their exceptional mechanical properties and high biocompatibility. However, their inherently inert surface limits osteogenic potential and makes them prone to bacterial colonization, increasing the risk of biofilm formation and implant-related infections. To address these limitations, surface modification of Ti is essential. This study aimed to enhance the surface properties of Ti by coating it with polydopamine (PDA) and further doping it with copper and calcium ions. TPDA was prepared and subsequently used to fabricate TPDA@Cu and TPDA@CuCa samples. Material characterization confirmed that TPDA@CuCa exhibited excellent surface wettability and biocompatibility, with Cu2 + and Ca2+ being continuously and stably released in liquid environments. Additionally, TPDA@CuCa significantly improved protein adsorption, facilitating favorable cellular interactions. In vitro experiments demonstrated that TPDA@CuCa exhibited strong antimicrobial activity against Escherichia coli and Staphylococcus aureus, enhanced osteoblast adhesion, mineralization, and upregulated osteogenic gene expression. This bifunctional surface modification strategy offers a promising approach to enhancing both the osteogenic and antibacterial properties of Ti implants.

Dynamic ion-releasing biomaterials have redefined the role of implantable bone devices, transitioning them from passive mechanical support to active players in tissue regeneration. These materials actively modulate the surrounding biological microenvironment by releasing bioactive ions (e.g.: calcium, phosphate, and cobalt) which dynamically interact with cells and tissues surrounding them. This interaction becomes the microenvironment highly active and accelerates bone healing, promoting osteogenesis, and enhancing osseointegration. The ions modulate key biological processes in this regard, including osteoblast adhesion, proliferation, differentiation, angiogenesis, and immune responses, as well as coupled physiological mechanisms, ensuring that the implanted biomaterials foster an optimal environment for bone regeneration. More advanced surface modifications onto materials (e.g.: nanostructuring hydroxyapatites coatings) have been shown to further boost ion release, amplifying the ability of the material to influence surrounding tissues. As a result, ion-releasing biomaterials not only improve implant integration but also accelerate the overall healing process. Looking forward, the development of smart biomaterials capable of adjusting ion release in response to environmental changes offers exciting possibilities for personalized regenerative therapies and this review provides a comprehensive understanding of how dynamic ion-releasing biomaterials actively shape the microenvironment to enhance healing, focusing on their ability to modulate biological processes such as osteogenesis and angiogenesis. By examining the latest advances in surface modifications and ion-release mechanisms, this review also aims to revise the potential of these materials to revolutionize regenerative medicine, offering knowledge to guide the development of next-generation biomaterials for improved clinical outcomes.

Polymer-based scaffolds for bone regeneration aim to mimic the structure and function of the collagen-rich extracellular matrix. Hydroxyapatite incorporated into these biomaterials improves their mechanical and biological properties due to its bioactive osteoconductive nature. The objectives of this study are to synthesize and characterize polycaprolactone (PCL) scaffolds containing hydroxyapatite nanoparticles (HAn) at 1, 2.5, 5, and 7% concentrations and to determine their cytocompatibility and osteogenic potential. Fiber thickness (n = 240) and interfibrillar space (n = 8) of PCL scaffolds were characterized by scanning electron microscopy (SEM). The PCL scaffolds were evaluated concerning their thermal degradation (TGA), calcium release, and hydrophilicity (WCA). Preosteoblasts were seeded on PCL scaffolds and assessed regarding their viability (AlamarBlue, n = 8), collagen synthesis (SR, n = 8), total protein synthesis (TP, n = 8), alkaline phosphatase activity (ALP, n = 8), deposition of mineralization nodules (MN, n = 8), and cell adhesion (fluorescence microscopy). The data analyses of the biomaterials, including TGA, energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR), were interpreted descriptively. The quantitative data were statistically analyzed (α = 5%). Scaffolds without HAn exhibited thicker fibers. The higher incorporation of HAn in the PCL scaffolds increased the interfibrillar spaces and resulted in greater P and Ca peaks (p < 0.05), as well as broader peaks representing the P-O group (FTIR). TGA demonstrated that PCL scaffold degradation was inversely proportional to their HAn concentration. Higher percentages of cell viability were observed with the incorporation of HAn. ALP activity increased in cells seeded onto PCL scaffolds containing 2.5% HAn. Deposition of MN was directly proportional to the amount of HAn incorporated. HAn incorporated into PCL scaffolds interferes with the physicochemical properties of these biomaterials and favors in vitro osteogenesis.

In recent years, notable advancements have been achieved in the domain of tissue engineering and regenerative medicine, presenting auspicious remedies for the management of diverse injuries and ailments. The management of bone injuries necessitates the implementation of a customized approach depending upon the specific nature of the injury. Tissue engineering plays a major role in the treatment of such bone injuries. One key aspect of tissue engineering is the development of scaffolds that can provide structural support and guide the growth of new tissue. The scaffold should possess mechanical properties that enable it to withstand weight-bearing stresses, resembling the strength and durability of real bone. This review explores the latest research findings from pioneering research papers in tissue engineering, focusing on scaffolds, bioceramics, and the various technique for the development of scaffolds with a focus on 3D printing. By examining and synthesizing key studies in these areas, this review aims to provide insights into the current state of knowledge, identify research gaps, and contribute to the advancement of tissue engineering approaches for regenerative medicine applications.

The enzymatic formation of calcium phosphate (CaP) in bone is a prime example of how living organisms utilize enzymes to precisely regulate biomineral nucleation and growth, serving as inspiration for the design of biomimetic nanomaterials. In this study, we investigated the formation mechanisms of enzymatic CaP in buffered solutions using single molecule enzymology and cryo-transmission electron microscopy to probe the relationship between tissue nonspecific alkaline phosphatase (TNALP) activity and CaP formation pathways. We characterized the dynamics of heterogeneous TNALP activity, which consists of singly and doubly active enzyme molecules during enzymatic CaP formation and identified two distinct formation pathways that produce amorphous calcium phosphate nanoparticles and octacalcium phosphate nanoparticles. These results show the complex and potentially powerful relationship between heterogeneous enzyme activity and CaP formation mechanisms, offering a new level of control in space and time for the design of biomimetic nanomaterials.

The field of bone tissue engineering is vital due to increasing bone disorders and limitations of traditional grafts. Injectable hydrogels offer minimally invasive solutions but often lack mechanical integrity and biological functionality, including osteoinductive capacity and structural stability under physiological conditions. To address these issues, we propose a coacervate-based injectable adhesive hydrogel that utilizes the dual functionality of in situ photocrosslinking and osteoinductive amorphous calcium phosphate formation, both of which are activated simultaneously by visible light irradiation. The developed hydrogel formulation integrated a photoreactive agent with calcium ions and phosphonodiol in a matrix of tyramine-conjugated alginate and RGD peptide-fused bioengineered mussel adhesive protein, promoting rapid setting, robust underwater adhesion, and bioactive mineral deposition. The hydrogel also exhibited superior mechanical properties, including enhanced underwater tissue adhesive strength and compressive resistance. In vivo evaluation using a rat femoral tunnel defect model confirmed the efficacy of the developed adhesive hydrogel in facilitating easy application to irregularly shaped defects through injection, rapid bone regeneration without the addition of bone grafts, and integration within the defect sites. This injectable adhesive hydrogel system holds significant potential for advancing bone tissue engineering, providing a versatile, efficient, and biologically favorable alternative to conventional bone repair methodologies.

This study aimed to evaluate the effects of the atomic layer deposited hydroxyapatite (ALD-HA) coating of the titanium (Ti) surface on human gingival keratinocyte (HGK) cell adhesion, spreading, viability, and hemidesmosome (HD) formation. Grade 2 square-shaped Ti substrates were used (n = 62). Half of the substrates were ALD-HA coated, while the other half were used as non-coated controls (NC). The ALD-HA surface was characterized with scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis. The initial cell adhesion and HD formation of HGKs were evaluated after a 24-h cultivation period. The cell proliferation was assessed by cultivating cells for 1, 3, and 7 d. The expression levels of the integrin mediating cell adhesion were detected with the Western Blot method. In addition, cell spreading and expression of the proteins mediating cell adhesion were imaged using a confocal microscope. SEM-EDS analysis demonstrated the formation of HA on the ALD-HA surfaces. The relative cell attachment was significantly higher (p < .05) on the ALD-HA compared to the NC surface after 1 and 3 d of cell culture. No significant difference was found in integrin α6 or β4 expression. The microscope evaluation showed significantly increased cell spreading with peripheral HD expression on ALD-HA compared to the NC surfaces (p = .0001). Moreover, laminin γ2 expression was significantly higher on the ALD-HA than on the NC surfaces (p < .001). Compared to the NC Ti surface, the ALD-HA coating has favorable effects on HGK proliferation, growth, and cell spreading. This indicates that the ALD-HA coating has good potential for improving mucosal attachment on implant surfaces.

In the repair of large bone defects, loss of the periosteum can result in diminished osteoinductive activity, nonunion, and incomplete regeneration of the bone structure, ultimately compromising the efficiency of bone regeneration. Therefore, the research and development of tissue-engineered periosteum which can replace the periosteum function has become the focus of current research. The functionalized electrospinning periosteum is expected to mimic the natural periosteum and enhance bone repair processes more effectively. This review explores the construction strategies for functionalized electrospun periosteum from the following perspectives: ⅰ) bioactive factor modification (bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) etc.), ⅱ) inorganic compound modification, ⅲ) drug modification, ⅳ) artificial periosteum in response to physical stimuli. Furthermore, the construction of artificial periosteum through electrospinning, in conjunction with other strategies, is also analyzed. Finally, the current challenges and prospects for the development of electrospinning periosteum are also discussed.

To evaluate cytotoxicity and tissue repair of a new chicken eggshell-derived bioceramic (hydroxyapatite/dicalcium phosphate anhydrous-HA/DCPA).

Cytotoxicity was evaluated in fibroblasts (L cell, L-929) by MTT test. Tissue repair of HA/DCPA was compared to HA/β-TCP bioceramic (Maxresorb-MXR). Two critical-sized bone defects (CSDs) were drilled in the calvarial of 24 Wistar rats and filled with one of the biomaterials. The animals were euthanized after 30, 60, and 90 days, and bone specimens were examined by histomorphometric analyses, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The percentages of newly formed bone, connective tissue, remaining biomaterial, and total tissue repair area were compared between groups using Student's t-test and analysis of variance (p ≤ 0.05).

HA/DCPA did not exhibit any cytotoxicity. CSDs contained newly formed bone from the defect margins and from ossification centers interspersed throughout the biomaterials. At 30 days, HA/DCPA group had a significantly larger total tissue repair area than MXR group (p = 0.047). No differences were observed between groups regarding variables studied (p > 0.05).

HA/DCPA is non-cytotoxic. This cement promoted new bone formation and tissue filling of the entire defect area with degree of biomaterial degradation similar to HA/β-TCP, proving to be equally suitable and successful for bone regeneration.

The effectiveness of antimicrobial ion-substituted calcium phosphate biomaterials has been investigated in numerous studies, but reporting guidelines and quality checklists are missing. A novel quality checklist was created for assessing reporting and methodological quality by experts of relevant disciplines. The checklist consisted of 20 items for reporting quality (maximum score 32) and 11 for methodological quality (maximum score 18). The checklist was subsequently implemented to assess the reporting and methodological quality of 58 studies in this field. Possible associations between study quality, year of publication and citations were investigated, and items for improvement were identified. Main items for improvement in reporting quality (average score 18/32) were reporting variability and statistics of data, reporting rationales for study design and the clinical relevance of the outcomes. Methodological quality (average score 11/18) could be improved by including positive control groups, using clinically relevant material formulations and including tests of the material toxicity. No association was found between study quality and year of publication. Methodological quality was associated with a higher number of annual citations. This study identifies key areas for improvement of reporting and methodological quality in the field of ion-substituted antimicrobial calcium phosphates. With these findings, the quality of future studies on antimicrobial CaP materials can be improved. The new quality checklist can also be used to improve study design for future research and enables better comparison between study outcomes.

In recent years, the management of bone defects in regenerative medicine and orthopedic surgery has been the subject of extensive research efforts. The complexity of fractures and bone loss arising from trauma, degenerative conditions, or congenital disorders necessitates innovative therapeutic strategies to promote effective healing. Although bone tissue exhibits an intrinsic regenerative capacity, extensive fractures and critical-sized defects can severely compromise this process, often requiring bone grafts or substitutes. Tissue engineering approaches within regenerative medicine have introduced novel possibilities for addressing nonunions and challenging bone defects refractory to conventional treatment methods. Key components in this field include stem cells, bioactive growth factors, and biocompatible scaffolds, with a strong focus on advancements in bone substitute materials. Both natural and synthetic substitutes present distinct characteristics and applications. Natural grafts-comprising autologous, allogeneic, and xenogeneic materials-offer biological advantages, while synthetic alternatives, including biodegradable and non-biodegradable biomaterials, provide structural versatility and reduced immunogenicity. This review provides a comprehensive analysis of the diverse bone grafting alternatives utilized in orthopedic surgery, emphasizing recent advancements and persistent challenges. By exploring both natural and synthetic bone substitutes, this work offers an in-depth examination of cutting-edge solutions, fostering further research and innovation in the treatment of complex bone defects.

Piezoelectricity is reported to be able to promote bone scaffolds with excellent osteogenic performance. Herein, barium titanate/β-tricalcium phosphate (BTO/β-TCP) piezoelectric composite scaffolds were 3D printed, and their osteogenic performances were investigated in detail. The fabrication of BTO/β-TCP piezoelectric composite scaffolds employed cutting-edge DLP 3D printing technology. The scaffolds, featuring a triply periodic minimal surface (TPMS) design with a porosity of 60%, offered a unique structural framework. A comprehensive assessment of the composition, piezoelectric properties, and mechanical characteristics of the BTO/β-TCP scaffolds was conducted. Notably, an increase in the BTO volume fraction from 50 to 80 vol % within the scaffolds led to a reduction in compressive strength, decreasing from 2.47 to 1.74 MPa. However, this variation was accompanied by a substantial enhancement in the piezoelectric constant d33, soaring from 1.4 pC/N to 21.6 pC/N. Utilizing mouse osteoblasts (MC3T3-E1) in a live/dead cell staining assay, under the influence of external ultrasound, demonstrated the commendable biocompatibility of these piezoelectric composite ceramic bone scaffolds. Furthermore, thorough analyses of alkaline phosphatase (ALP) activity and polymerase chain reaction (PCR) findings provided compelling evidence of the scaffolds' superior osteogenic properties, underpinning their effectiveness at the cellular protein and gene levels. In conclusion, this study offers a groundbreaking strategy for the employment of BTO/β-TCP piezoelectric composite scaffolds in bone implant applications, harnessing their unique blend of biocompatibility, piezoelectricity, and osteogenic potential.

Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel solutions for treating bone defects, surpassing the use of traditional autologous grafts. This review aims to assess the latest approaches in bone regeneration, including autologous, allogenic, and xenogenic grafts, naturally derived biomaterials, and innovative synthetic substitutes such as bioceramics, bioactive glasses, metals, polymers, composite materials, and other specialized applications. A comprehensive literature search was conducted on PubMed, focusing on studies published between 2019 and 2024, including meta-analyses, reviews, and systematic reviews. The review evaluated a range of bone regeneration strategies, examining the clinical outcomes, materials used, surgical techniques, and the effectiveness of various approaches in treating bone defects. The search identified numerous studies, with the inclusion criteria focused on those exploring innovative bone regeneration strategies. These studies provided valuable insights into the clinical and biological outcomes of different biomaterials and graft types. Results indicated that while advancements in synthetic and naturally derived biomaterials show promising potential, challenges remain in optimizing therapeutic strategies across diverse patient populations and clinical settings. The findings emphasize the need for an integrated approach that combines scientific research, clinical practice, and technological innovation to improve bone regeneration therapies. Further research is required to establish standardized protocols and determine the optimal application of various materials and techniques to enhance patient outcomes and the quality of care.

The increasing demand for titanium implants necessitates improved longevity. Plasma-sprayed hydroxyapatite coatings enhance implant osseointegration but are susceptible to delamination. Alternatively, anodized hydroxyapatite coatings have shown greater adhesion strengths. The present study aimed to develop anodized hydroxyapatite coatings on titanium using commercial calcium-fortified fruit juice as a calcium source. Varying the electrolyte compositions enabled the formation of four oxide groups with different predominate calcium compounds. Each oxide's morphology, crystallinity, chemistry, molecular structure, and adhesion quality were compared and contrasted. Nanoscale SEM images revealed a progression from porous surface oxide to white surface deposits to petal-like hydroxyapatite structures with the changing anodization electrolytes. Oxide thickness evaluations showed progression from a single-layered oxide with low Ca-, P-, and Mg-dopant incorporations to bi-layered oxide structures with increased Ca-, P-, and Mg-dopant incorporation with changing electrolytes. The bi-layered oxide structures exhibited a titanium-dioxide-rich inner layer and calcium-compound-rich outer layers. Furthermore, indentation analyses confirmed good adhesion quality for three oxides. For the predominate hydroxyapatite oxides, FTIR analyses showed carbonate substitutions indicating the presence of bone-like apatite formation, and ICP-OES analyses revealed prolonged Ca and Mg release over 30 days. These Mg-enhanced carbonated apatite coatings show much promise to improve osseointegration and future implant lifetimes.

Bone injuries remain a significant challenge, driving the development of new materials and technologies to enhance healing. This study presents a novel approach for incorporating graphene into calcium phosphate (CaP) coatings on titanium alloy (Ti) substrates, with the aim of creating a new generation of materials for bone implant electronics. The stability of the composite coating under physiological conditions, long-term electrical and mechanical durability, and biocompatibility were systematically investigated. We integrated graphene into the CaP coating through the laser processing of diazonium-functionalized graphene films applied to the surface of CaP-coated Ti. The laser treatment induced several processes, including the removal of aryl groups, the formation of conductive pathways, and chemical bonding with the CaP film. As a result, the graphene-CaP nanocomposite demonstrated excellent mechanical durability, withstanding a 2 h sand abrasion test. It also exhibited excellent biocompatibility, as shown by the proliferation of human fibroblast cells for 7 days. The electrical properties remained stable under physiological conditions for 12 weeks, and the material maintained electrochemical stability after 1 million pulse cycles. Furthermore, it withstood the stress of 100,000 bending cycles without compromising electrical performance. This work highlights the versatility of the biocompatible graphene composite and its potential for a range of applications including free-form electronic circuits, electrodes, bending sensors, and electrothermal heaters.

Tissue-derived extracellular matrix (tdECM) hydrogels serve as effective scaffolds for tissue regeneration by promoting a regenerative immune response. While most tdECM hydrogels are nanoporous and tailored for soft tissue, macroporosity is crucial for bone regeneration. Yet, there's a shortage of macroporous ECM-based hydrogels for this purpose. The study aims to address this gap by developing a co-spinning technique to integrate bone-derived ECM (bECM) into gelatin-based, macroporous microribbon (µRB) scaffolds. The effect of varying doses of bECM on scaffold properties was characterized. In vitro studies revealed 15% bECM as optimal for promoting MSC osteogenesis and macrophage (Mφ) polarization. When implanted in a mouse critical-sized cranial bone defect model, 15% bECM with tricalcium phosphate (TCP) microparticles significantly accelerated bone regeneration and vascularization, filling over 55% of the void by week 2. Increasing bECM to 25% enhanced mesenchymal stem cell (MSC) recruitment and decreased M1 Mφ polarization but reduced overall bone formation and vascularization. The findings demonstrate co-spun gelatin/bECM hydrogels as promising macroporous scaffolds for robust endogenous bone regeneration, without the need for exogenous cells or growth factors. While this study focused on bone regeneration, this platform holds the potential for incorporating various tdECM into macroporous scaffolds for diverse tissue regeneration applications.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are two common dental regenerative procedures used to repair periodontal defects caused by periodontitis. In both procedures, a barrier membrane is placed at the interface between the soft tissue and the periodontal defect, serving to impede the infiltration of soft tissue while creating a secluded space for periodontal regeneration. Recently, barrier membranes based on chitosan (CS) have emerged as a promising avenue for these applications. However, despite numerous studies on the development of CS-based membranes, comprehensive review articles specifically addressing their progress in GTR/GBR applications remain scarce. Herein, we review recent research and advancements in the use of CS-based membranes for periodontal GTR and GBR. The review begins by highlighting the advantageous properties of CS that make it a suitable biomaterial for GTR/GBR applications. Next, the development of composite CS-based membranes, reinforced with various compositions like bioactive fillers and therapeutic agents, is discussed in detail based on recent literature, with a focus on their enhanced efficacy in promoting periodontal regeneration. Finally, the review explores the emergence of functionally graded CS-based membranes, emphasizing their potential to address specific challenges encountered in GTR/GBR procedures.

This study investigates the effects of different treatment sequences involving demineralization, brushing, and remineralization on the calcium and phosphorus (Ca/P) content, surface roughness, and microhardness of dentin specimens. Bovine dentin samples were subjected to the following five treatment conditions: control, demineralization, demineralization followed by remineralization, demineralization followed by brushing then remineralization, and demineralization followed by remineralization then brushing. X-ray fluorescence spectroscopy was then utilized to assess the elementary composition changes, while scanning electron microscopy provided microstructural analyses. Surface roughness and microhardness were also quantified to assess the physical changes in dentin. The control group retained significantly higher Ca/P content compared with all treated groups, indicating that demineralization, regardless of subsequent treatment, leads to a substantial loss of hydroxyapatite. Among the treated groups, those that underwent remineralization immediately after demineralization manifested higher Ca/P retention compared with those that included brushing before remineralization. Additionally, microhardness measurements indicated that post-demineralization brushing negatively affected dentin's microhardness. The sequence of demineralization, brushing, and remineralization treatments significantly affects Ca/P retention in dentin, along with its surface roughness and microhardness. Pre-remineralization brushing diminished mineral recovery, whereas exposure to mineral-rich beverage immediately after demineralization resulted in greater mineral deposition.

Autografts, allografts, and synthetic bone substitutes are essential in reconstructive orthopedic surgery. Although autografts and allografts provide excellent skeletal integration, their use is limited by host morbidity and graft acquisition challenges. Synthetic materials like β-tricalcium phosphate (β-TCP) offer promising osseoconductive properties as a potential substitute. This study evaluated the osseointegration of β-TCP ceramic cylinder implants in bone defects in rabbits. Eighteen New Zealand rabbits underwent radial diaphysis ostectomy to create a critical segmental defect and were divided into three groups: Group A received β-TCP blocks, Group B received allogenous cortical bone grafts, and Group C underwent ostectomy without defect filling. Postoperative assessments included clinical evaluations, radiographs, micro-computed tomography, and histology at various time points to assess osseointegration and implant resorption. At the 120th postoperative day, Group B showed successful bone integration without infection. In contrast, Group A showed no osseointegration or resorption of the β-TCP implants, and Group C exhibited bone non-union. While β-TCP demonstrated biocompatibility, it lacked osseoconductivity, likely due to low porosity. β-TCP implants did not promote bone consolidation, suggesting that further research on porosity and shape is needed to improve their suitability for veterinary orthopedic reconstructive surgery.

Magnesium-doped hydroxyapatite/chitosan composite coatings produced by the radio-frequency magnetron sputtering technique were exposed to 5 MeV electron beams of 8 and 30 Gy radiation doses in a linear electron accelerator. The surfaces of unirradiated layers are smooth, while the irradiated ones exhibit nano-structures with sizes that increase from 60 nm at a 8 Gy dose to 200 nm at a 30 Gy dose. Young's modulus and the stiffness of the layers decrease from 58.9 GPa and 10 µN/nm to 5 GPa and 2.2 µN/nm, respectively, when the radiation doses are increased from 0 to 30 Gy. These data suggest the diminishing of the contribution of the chitosan to the elasticity of the magnesium-doped hydroxyapatite/chitosan composite layers after electron beam irradiation. The biological capabilities of the coatings were assessed before and after their immersion in RPMI-1640 cell culture medium for 7 and 14 days, respectively, and further cultured with a MG63 cell line (ATCC CRL1427) in Dulbecco's Modified Eagle Medium supplemented with fetal bovine serum, penicillin-streptomycin, and L-glutamine. Thus, 1 µm spherical structures were developed on the surfaces of the layers exposed to a 30 Gy radiation dose and immersed for 14 days in the RPMI-1640 biological medium. The molecular structures of all the RPMI-1640 immersed samples were modified by the growth of a carbonated hydroxyapatite layer characterized by a B-type substitution, as Fourier Transform Infrared Spectroscopy revealed. The biological assay proved the increased biocompatibility of the layers kept in RPMI-1640 medium and enhanced MG63 cell attachment and proliferation. Atomic force microscopy analysis indicated the elongated fibroblastic cell morphology of MG63 cells with minor alteration at 30 Gy irradiation doses as a result of layer biocompatibility modifications.

Bone metastasis remains one of the biggest challenges in the treatment of prostate cancer, and other solid tumors such as breast, lung, and colon. Modeling a complex microenvironment in-vitro such as the bone niche, requires interrogation of cell-cell interactions, specific extracellular matrix proteins, and a high calcium environment.

Here, we present a fast and cost-effective system in which commercially available, non-adhesive cell culture vessels are coated with amorphous calcium phosphate (ACP) as a surrogate for bone matrix. We also present modified protocols for subculturing cells and collecting nucleic acids and protein in high-calcium samples.

We find that prostate epithelial cell lines show increased adhesion and proliferation when cultured in these amorphous calcium surfaces, accompanied by independence from androgen starvation. We observe gene expression changes on ACP surfaces in early adenocarcinoma cell lines which match alterations relevant to prostate cancer progression.

Incorporating biologically relevant in-vitro systems that address the microenvironment milieu of the metastatic site is essential for accurately modeling cancer progression. In the case of bone metastasis, calcium availability, uptake, and downstream signaling are of paramount importance for the survival of the cancer cell and should be considered in the development of pre-clinical models.

Polyetheretherketone (PEEK) is a high-performance polymer material for developing varying orthopedic, spine, cranial, maxillofacial, and dental implants. Despite their commendable mechanical properties and biocompatibility, the major limitation of PEEK implants is their low affinity to osseointegrate with the neighboring bone. Over the last two decades, several efforts have been made to incorporate bioactive components such as bioceramic particles in PEEK to enhance its osseointegration capacity. However, one major limitation is that the bioceramic particles embedded in the PEEK matrix can degrade over time, compromising the implant's long-term bioactivity and mechanical properties. To address this limitation, in this study, we utilized a unique bioceramic known as amorphous magnesium phosphate (AMP). AMP is a metastable phase of magnesium phosphate that nanocrystallizes in a physiological medium to stable bioactive phases exhibiting low degradation kinetics and high bioactivity. Thus, based on this property of AMP, we hypothesize that AMP-PEEK composites will exhibit sustained biodegradation kinetics, help maintain long-term osseointegration, and inhibit mechanical property degradation. Herein, we reported on a detailed in vitro degradation analysis of the developed AMP-PEEK composite 3D-printable filaments and the osseointegration capacity when implanted in a rat femoral model. The AMP-PEEK composite demonstrates controlled degradation kinetics, with tensile strength progressively decreasing from 120 to 70 MPa over a 28-day period due to hydrolytic degradation, which aligns with its role as a bioresorbable material. Notably, our findings confirm that AMP-PEEK composite osseointegration is on par with clinical gold-standard titanium implants. Thus, this study establishes a unique magnesium phosphate and PEEK-based bioactive composite material with promising potential for developing standalone dental and craniofacial implants.

Nanocomposite hydrogels have potential in bone regeneration due to the inorganic and polymeric material content. In this study, new types of nanocomposite hydrogels composed of zoledronic acid/strontium hydroxyapatite nanoparticles and carboxymethyl chitosan/oxidized dextran (CMC/OD) hydrogels were reported. Pure hydroxyapatite, 5%, 10% and 15% (w/w) strontium-substituted strontium hydroxyapatite nanoparticles were produced and then modified with zoledronic acid at ratios of 5% to 7.5% (w/w). These modified structures were then incorporated into CMC/OD hydrogels. Zoledronic acid modified strontium hydroxyapatite nanoparticles were characterized using Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Diffraction (XRD). CMC/OD structures were investigated using Fourier Transform Infrared Analysis (FTIR), Scanning Electron Microscopy (SEM). The physical properties of the hydrogels were determined via degradation behavior and rheological measurements. Cell-material interactions were investigated in vitro. The results showed that the incorporation of hydroxyapatite nanoparticles into CMC would significantly improve the rheological properties. The addition of strontium to hydroxyapatite nanoparticles significantly enhanced cell proliferation. In addition, a significant increase in alkaline phosphatase (ALP) and calcium deposition was observed with the addition of zoledronic acid. In conclusion, the nanocomposite hydrogels of CMC/OD containing zoledronic acid modified strontium hydroxyapatite demonstrate potential for orthopedic and craniofacial applications due to their superior properties, including the ability to be easily injected into targeted areas, potent antibacterial activity that helps prevent infections and remarkable self-healing capabilities that promote tissue regeneration and repair.

To carry out physicomechanical characterization of the HA/DCPA/TiO2 and to evaluate the tissue repair in rat calvaria.

Two bone defects were made in the calvaria of 36 Wistar rats, divided into groups: HA/DCPA, HA/DCPA/TiO2 and sham (blood clot). The animals were euthanized at 30, 60 and 90 days and calvaria slides were processed with hematoxylin/eosin. The newly formed bone, connective tissue, biomaterial remnant, and total tissue repair percentages were calculated in relation to the total defect area. The HA/DCPA/TiO2 was characterized structurally by scanning electron microscopy (SEM), and chemically by energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). It was submitted to apparent density (AD), apparent porosity (AP), water absorption (WA) and compressive strength (CS) physical tests. The ANOVA test was applied, followed by Turkey's test and Student's t-test (p ≤ 0,05).

The SEM showed biomaterials inside the bone defects and newly formed bone. EDS identified oxygen, calcium, phosphorus, and titanium in the sample. The HA/DCPA/TiO2 and HA/DCPA groups presented a total tissue repair area that was larger than the sham group (p < 0.001).

The physical-mechanical assays showed that HA/DCPA/TiO2 has AD and CS properties within the limits of trabecular bone and with values higher than HA/DCPA.HA/DCPA/TiO2 presented higher densification and compressive strength rates than HA/DCPA.

Potential as a scaffold for bone.

Bone fractures must undergo a complex healing process involving intricate cellular and molecular mechanisms. They require a suitable biological environment to restore skeletal stability and resolve inflammation. Scaffolds play a vital role in bone regeneration, thus reducing disease burden. Autologous bone graft represents the gold standard of therapy. However, its application is limited due to various reasons. Nanotechnology, in the form of nanomaterials and nano-drug delivery systems, has been proven to increase the potency of active substances in mimicking extracellular matrix (ECM), thereby providing physical support benefits and enhancing therapeutic effectiveness. Various materials, including protein, metal oxide, hydroxyapatite, and silica are modified with nanoparticle technology for the purposes of tissue regeneration therapy. Moreover, the properties of nanomaterials such as size, seta potential, and surface properties will affect their effectiveness in bone regeneration therapy. This review provides insights that deepen the knowledge of the manufacturing and application of nanomaterials as a therapeutic agent for bone regeneration.

This first randomized controlled trial in humans aimed to assess the efficacy and safety of low-dosage Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2)-incorporated biomimetic calcium phosphate coating-functionalized β-TCP (ErhBMP-2/BioCaP/β-TCP) as a novel bone substitute using the tooth-extraction-socket-healing model.

Forty patients requiring dental implants after single-root tooth extraction were enrolled in this study and randomly assigned into three groups: ErhBMP-2/BioCaP/β-TCP (N = 15), β-TCP (N = 15) and natural healing (N = 10). New bone volume density from histomorphometric analyses was evaluated 6 weeks post-operatively as the primary outcome, and other histomorphometric analyses, alveolar bone and soft-tissue changes were the secondary outcomes. Safety parameters included adverse events, soft-tissue healing, oral health impact profile, serum BMP-2 concentrations and other laboratory tests.

The findings revealed a significant increase in new bone volume density in patients treated with ErhBMP-2/BioCaP/β-TCP compared to those receiving β-TCP alone. The required bone augmentation procedures during implant placement surgery in the ErhBMP-2/BioCaP/β-TCP group were significantly less than in the natural healing group. There were no significant differences in safety parameters among the three groups.

This clinical trial primarily proved the safety and efficacy of ErhBMP-2/BioCaP/β-TCP as a promising bone substitute.

Guided bone regeneration (GBR) typically involves bone grafts and a membrane to enhance bone formation. Beta-tricalcium phosphate calcium sulfate (β-TCP/CS) is a novel material with self-hardening and tissue growth inhibition properties and can potentially replace the need for a membrane. This study compares β-tricalcium phosphate/calcium sulfate with deproteinized bovine bone mineral and a collagen membrane (DBBM/CM) to repair bone defects at implant sites over 6 months. Sixteen implant defects were divided into β-TCP/CS (n = 8) and DBBM/CM (n = 8). The results showed no significant differences in vertical and horizontal defect fill in millimeters between β-TCP/CS (2.87 ± 1.25 and 2.37 ± 1.06 mm, respectively) and DBBM/CM (3.5 ± 0.92 and 2.87 ± 1.12 mm, respectively). Buccal bone thickness (BT) alterations at the implant platform levels (BT0) were similar for both materials. However, β-TCP/CS exhibited greater bone alteration at the 2-mm level (BT2: -1.85 mm vs -0.47 mm) and 4-mm level (BT4: -1.79 mm vs 0.12 mm) apical to the implant platform compared to DBBM/CM. When assessing volume alteration, β-TCP/CS showed a significantly greater reduction at the platform to the 2 mm level (-61.98% vs -23.76%) than DBBM/CM. In conclusion, β-TCP/CS demonstrated promise for treating buccal bone defects around implants but exhibited higher graft reduction. This suggests that while β-tricalcium phosphate/calcium sulfate may offer clinical benefits, its potential for greater graft reduction should be considered. Further research and evaluation are warranted to fully understand the long-term implications of using β-TCP/CS in guided bone regeneration procedures.

An ideal biomimetic periosteum should have excellent biocompatibility to promote osteoclast adhesion and improve osseointegration, which is significant in promoting bone regeneration. In this work, a bionic artificial periosteum printed by the SLA-3D printing was prepared, consisting of a poly (ethylene glycol) diacrylate (PEGDA)/chitosan/tricalcium phosphate (TCP) fibrous layer and a gelatin methacryloyl (GelMA)/ammonium molybdate (Mo) cambium layer. Distinct surface characteristics were achieved on both sides of the biomimetic periosteum. Among them, the fibrous layer has high mechanical properties and low porosity, which is conducive to preventing the pulling of muscle tissues and the invasion of soft tissues. The cambium layer has a porous structure and bioactive factors that can effectively promote osteogenic differentiation of preosteoblasts. Combined with mild photothermal therapy triggered by NIR light, the biomimetic periosteum could promote bone regeneration at both the chemical and physical levels. This 3D-printed bilayer hydrogel can provide a promising strategy for preparing advanced tissue-engineered periosteum with excellent physical and bone regeneration properties.

Spinal fusion surgery remains a significant challenge due to limitations in current bone graft materials, particularly in terms of bioactivity, integration, and safety. This study presents an innovative approach using an injectable hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) hydrogel combined with stromal vascular fraction (SVF) and low-dose recombinant human BMP-2 (rhBMP-2) to enhance osteodifferentiation and angiogenesis. Through a series of in vitro studies and preclinical models involving rats and minipigs, we demonstrated that the hydrogel system enables the sustained release of rhBMP-2, resulting in significantly improved bone density and integration, alongside reduced inflammatory responses. The combination of rhBMP-2 and SVF in this injectable formulation yielded superior spinal fusion outcomes, with enhanced mechanical properties and increased bone mass in both small and large animal models. These findings suggest that this strategy offers a promising and safer alternative for spinal fusion, with strong potential for clinical application.

Nucleic acid delivery with mRNA lipid nanoparticles are being developed for targeting a wide array of tissues and cell types. However, targeted delivery to the bone microenvironment remains a significant challenge in the field, due in part to low local blood flow and poor interactions between drug carriers and bone material. Here we report bone-targeting ionizable lipids incorporating a piperazine backbone and bisphosphate moieties, which bind tightly with hydroxyapatite ([Ca5(PO4)3OH]), a key component of mineralized tissues. These lipids demonstrate biocompatibility and low toxicity in both vitro and in vivo studies. LNP formulated with these lipids facilitated efficient cellular transfection and improved binding to hydroxyapatite in vitro, and targeted delivery to the bone microenvironment in vivo following systemic administration. Overall, our findings demonstrate the critical role of the piperazine backbone in a novel ionizable lipid, which incorporates a bisphosphonate group to enable efficient bone-targeted delivery, highlighting the potential of rational design of ionizable lipids for next-generation bone-targeting delivery systems.

Bone tissue engineering aims to develop biomaterials that are capable of effectively repairing and regenerating damaged bone tissue. Among the various polymers used in this field, polycaprolactone (PCL) is one of the most widely utilized. As a biocompatible polymer, PCL is easy to fabricate, cost-effective, and offers consistent quality control, making it a popular choice for biomedical applications. However, PCL lacks inherent antibacterial properties, making it susceptible to bacterial adhesion and biofilm formation, which can lead to implant failure. To address this issue, this study aims to enhance the antibacterial properties of PCL by incorporating calcium phosphate composite (PCL_CaP) nanostructures onto its surface via hydrothermal synthesis. The resulting "PCL_CaP" nanostructured surfaces exhibited improved wettability and demonstrated mechano-bactericidal potential against Escherichia coli and Bacillus subtilis. The flake-like morphology of the fabricated CaP nanostructures effectively disrupted bacteria membranes, inhibiting bacterial growth. Furthermore, the "PCL_CaP" surfaces supported the adhesion, proliferation, and differentiation of pre-osteoblasts, indicating their potential for bone tissue engineering applications. This study demonstrates the promise of calcium phosphate composite nanostructures as an effective antibacterial coating for implants and medical devices, with further research required to evaluate their long-term stability and in vivo performance.