Effect of bioceramic inclusions on gel-cast aliphatic polymer membranes for bone tissue engineering applications: An in vitro study.

BACKGROUND: Polylactic acid (PLA) has been extensively used in tissue engineering. However, poor mechanical properties and low cell affinity have limited its pertinence in load bearing bone tissue regeneration (BTR) devices. OBJECTIVE: Augmenting PLA with ß-Tricalcium Phosphate (ß-TCP), a calcium phosphate-based ceramic, could potentially improve its mechanical properties and enhance its osteogenic potential. METHODS: Gels of PLA and ß-TCP were prepared of different % w/w ratios through polymer dissolution in acetone, after which polymer-ceramic membranes were synthesized using the gel casting workflow and subjected to characterization. RESULTS: Gel-cast polymer-ceramic constructs were associated with significantly higher osteogenic capacity and calcium deposition in differentiated osteoblasts compared to pure polymer counterparts. Immunocytochemistry revealed cell spreading over the gel-cast membrane surfaces, characterized by trapezoidal morphology, distinct rounded nuclei, and well-aligned actin filaments. However, groups with higher ceramic loading expressed significantly higher levels of osteogenic markers relative to pure PLA membranes. Rule of mixtures and finite element models indicated an increase in theoretical mechanical strength with an increase in ß-TCP concentration. CONCLUSION: This study potentiates the use of PLA/ß-TCP composites in load bearing BTR applications and the ability to be used as customized patient-specific shape memory membranes in guided bone regeneration.

Development of electrospun electroactive polyurethane membranes for bone repairing.

To fabricate electroactive fibrous membranes and provide simulated bioelectric micro-environment for bone regeneration mimicking nature periosteum, a series of electroactive polyurethanes (PUAT) were synthesized using amino-capped aniline trimers (AT) and lysine derivatives as chain extenders. These PUAT were fabricated into fibrous membranes as guided bone tissue regeneration membranes (GBRMs) via electrospinning. The ultraviolet-visible (UV-vis) absorption spectroscopy and cyclic voltammetry (CV) of PUAT copolymers showed that the electroactive PUAT fibrous membranes had good electroactivity. Besides, the introduction of AT significantly improved the hydrophobicity and thermal stability of PUAT fibrous membranes and decreased the degradation rate of PUAT fibers in vitro. With the increasing content of AT incorporated into copolymers, the tensile strength and Young's modulus of PUAT fibrous membranes increased from 4 MPa (PUAT0) to 15 MPa (PUAT10) and from 2.1 MPa (PUAT0) to 18 MPa (PUAT10), respectively. The cell morphology and proliferation of rat mesenchymal stem cells (rMSCs) on PUAT fibers indicated that the incorporation of AT enhanced the cell attachment and proliferation. Moreover, the expression levels of OCN, CD31, and VEGF secreted by rMSCs on PUAT fibers increased with the increasing content of AT. In conclusion, an electroactive polyurethane fibrous membrane mimicking natural periosteum was prepared via electrospinning and showed good potential application in guiding bone tissue regeneration.

Calcium silicate cements endowing bioactivity and sustaining mechanical strength of low-heat-releasing and fast-curing magnesium phosphate cements.

It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What's more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by µCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustains mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.

Toxicological Assessment of Biodegradable Poli-ε-Caprolactone Polymer Composite Materials Containing Hydroxyapatite, Bioglass, and Chitosan as Potential Biomaterials for Bone Regeneration Scaffolds.

Polycaprolactone (PCL) is a biodegradable polyester that might be used in tissue engineering to obtain scaffolds for bone reconstruction using 3D-printing technologies. New material compositions based on PCL, with improved physicochemical properties and excellent biocompatibility, would improve its applicability in bone regeneration. The aim of this study was to assess the potential toxic effects of PCL-based composite materials containing 5% hydroxyapatite (PCL/SHAP), 5% bioglass (PCL/BIO), or 5% chitosan (PCL/CH) on MG-63 human fibroblast-like cells in vitro. Material tests were carried out using X-ray diffraction, differential thermal analysis/thermal gravimetry, BET specific surface analysis, and scanning electron microscopy. The effect of the biomaterials on the MG-63 cells was then assessed based on toxicity tests using indirect and direct contact methods. The analysis showed that the tested biomaterials did not significantly affect cell morphology, viability, proliferation, or migration. We concluded that biodegradable PCL-based scaffolds may be suitable for tissue scaffold production, and the addition of bioglass improves the growth of cultured cells.

Enhanced Osteogenesis in 2D and 3D Culture Systems Using RGD Peptide and α-TCP Phase Transition within Alginate-Based Hydrogel.

Cell-laden hydrogels have been extensively investigated in various tissue engineering fields by their potential capacity to deposit numerous types of cells in a specific area. They are largely used in soft-tissue engineering applications because of their low mechanical strength. In addition, sodium alginate is well-known for its encapsulation, loading capacity and for being easily controllable; however, it lacks cell-binding ligands and hence the ability to adhere cells. In this study, it is aimed to enhance osteogenesis in cells encapsulated in alginate and improve its mechanical properties by introducing a synthetic peptide and calcium phosphate phase transition. To increase cell-hydrogel interactions and increasing cell viability, an RGD peptide is added to a photocrosslinkable methacrylate-modified alginate, and alpha-tricalcium phosphate (α-TCP) is added to the hydrogel to increase its mechanical strength via phase transition. Cell proliferation, growth, and differentiation are assessed in both 2D and 3D cell cultures. The addition of α-TCP significantly improved the mechanical properties of the hydrogel. Moreover, the RGD peptide and α-TCP showed a synergistic effect with significantly improved cell adhesion and osteogenesis in both 2D and 3D cell cultures. Therefore, the functional hydrogel developed in this study can potentially be used for bone tissue regeneration.

Nanomaterial-integrated injectable hydrogels for craniofacial bone reconstruction.

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.

Exploring the application of piezoelectric ceramics in bone regeneration.

Piezoelectric ceramics are piezoelectric materials with polycrystalline structure and have been widely used in many fields such as medical imaging and sound sensors. As knowledge about this kind of material develops, researchers find piezoelectric ceramics possess favorable piezoelectricity, biocompatibility, mechanical properties, porous structure and antibacterial effect and endeavor to apply piezoelectric ceramics to the field of bone tissue engineering. However, clinically no piezoelectric ceramics have been exercised so far. Therefore, in this paper we present a comprehensive review of the research and development of various piezoelectric ceramics including barium titanate, potassium sodium niobate and zinc oxide ceramics and aims to explore the application of piezoelectric ceramics in bone regeneration by providing a detailed overview of the current knowledge and research of piezoelectric ceramics in bone tissue regeneration.

Optimization of Biologically Inspired Electrospun Scaffold for Effective Use in Bone Regenerative Applications.

Human bone is composed of organic and inorganic composite materials, contributing to its unique strength and flexibility. Hydroxyapatite (HAP) has been extensively studied for bone regeneration, due to its excellent bioactivity and osteoconductivity, which makes it a highly valuable biomaterial for tissue engineering applications. For better therapeutic effects, composite nanofibers containing polyvinyl alcohol (PVA) and polyvinyl Pyrrolidone (PVP) were developed using an electrospinning technique in this study. Herein, hydroxyapatite (a major inorganic constituent of native bone) concentrations varying from 5 to 25% were reinforced in the composite, which could alter the properties of nanofibers. The as-prepared composite nanofibers were characterized by SEM, TEM, XRD, and FT-IR spectroscopy, and a bioactivity assessment was performed in simulated body fluid (SBF). The ICP-OES analysis was used to determine the concentration of Ca2+ and PO42- ions before and after SBF immersion. To optimize the material selection, the nanofibrous scaffolds were subjected to cell proliferation and differentiation in MG-63 osteoblast cell lines, but no significant toxicity was observed. In conclusion, HAP-PVA-PVP scaffolds exhibit unique physical and chemical properties and ideal biocompatibility, with great promise to serve as effective candidates for bone tissue applications.

Spatiotemporal controlled released hydrogels for multi-system regulated bone regeneration.

Bone defect is one of the urgent problems to be solved in clinics, and it is very important to construct efficient scaffold materials to facilitate bone tissue regeneration. Hydrogels, characterized by their unique three-dimensional network structure, serve as excellent biological scaffold materials. Their internal pores are capable of loading osteogenic drugs to expedite bone formation. The rate and quality of new bone formation are intimately linked with immune regulation and vascular remodeling. The strategic sequential release of drugs to balance inflammation and regulate vascular remodeling is crucial for initiating the osteogenic process. Through the design of hydrogel microstructures, it is possible to achieve sequential drug release and the drug action time can be prolonged, thereby catering to the multi-systemic collaborative regulation needs of osteosynthesis. The drug release rate within the hydrogel is governed by swelling control systems, physical control systems, chemical control systems, and environmental control systems. Utilizing these control systems to design hydrogel materials capable of multi-drug delivery optimizes the construction of the bone microenvironment. Consequently, this facilitates the spatiotemporal controlled released of drugs, promoting bone tissue regeneration. This paper reviews the principles of the controlled release system of various sustained-release hydrogels and the advancements in research on hydrogel multi-drug delivery systems for bone tissue regeneration.

Stimuli-Responsive Codelivery System-Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-Intensity Pulsed Ultrasound to Enhance Osteogenesis Properties.

The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell growth and preventing rapid release or loss of effectiveness. We synthesized biocompatible and biodegradable scaffolds designed for the controlled codelivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2). Active agents in dendritic silica/titania mesoporous nanoparticles (DSTNs) were incorporated at different weight percentages (0, 2, 5, 7, 9, and 10 wt %) into a matrix of polycaprolactone (PCL) and polyethylene glycol (PEG) nanofibers, forming the CUR-BMP-2@DSTNs/PCL-PEG delivery system (S0, S2, S5, S7, S9, and S10, respectively, with the number showing the weight percentage). To enhance the formation process, the system was treated using low-intensity pulsed ultrasound (LIPUS). Different advanced methods were employed to assess the physical, chemical, and mechanical characteristics of the fabricated scaffolds, all confirming that incorporating the nanoparticles improves their mechanical and structural properties. Their hydrophilicity increased by approximately 25%, leading to ca. 53% enhancement in their water absorption capacity. Furthermore, we observed a sustained release of approximately 97% for CUR and 70% for BMP-2 for the S7 (scaffold with 7 wt % DSTNs) over 28 days, which was further enhanced using ultrasound. In vitro studies demonstrated accelerated scaffold biodegradation, with the highest level observed in S7 scaffolds, approximately three times higher than the control group. Moreover, the cell viability and proliferation on DSTNs-containing scaffolds increased when compared to the control group. Overall, our study presents a promising nanocomposite scaffold design with notable improvements in structural, mechanical, and biological properties compared to the control group, along with controlled and sustained drug release capabilities. This makes the scaffold a compelling candidate for advanced bone tissue engineering and regenerative therapies.

Hydroxyapatite synthesis and characterization from waste animal bones and natural sources for biomedical applications.

Hydroxyapatites (HAps) synthesized from waste animal bones have recently gained attention due to their outstanding properties. This is because there is a need to fabricate scaffolds with desirable mechanical strength, ability to withstand high temperatures, and insoluble in solvents such as water, acetone, ethanol, and isopropyl alcohol. This study is an extensive summary of many articles on the routes of synthesis/preparation of HAp, and the optimum processing parameter, and the biomedical application areas, such as: drug administration, dental implants, bone tissue engineering, orthopedic implant coatings, and tissue regeneration/wound healing. A broad catalog of the synthesis methods (and combination methods), temperature/time, shape/size, and the calcium-to-phosphorous (Ca/P) value of diverse waste animal bone sources were reported. The alkaline hydrolysis method is proposed to be suitable for synthesizing HAp from natural sources due to the technique's ability to produce intrinsic HAp. The method is also preferred to the calcination method owing to the phase transformation that takes place at high temperatures during calcinations. However, calcinations aid in removing impurities and germs during heating at high temperatures. When compared to calcination technique, alkaline hydrolysis method results in crystalline HAp; the higher degree of crystallinity is disadvantageous to HAp bioactivity. In addition, the standardization and removal of impurities and contaminants, thorough biocompatibility to ensure clinical safety of the HAp to the human body, and improvement of the mechanical strength and toughness to match specific requirements for the various biomedical applications are the important areas for future studies.

Exosome-loaded hydrogels for craniofacial bone tissue regeneration.

It is common for maladies and trauma to cause significant bone deterioration in the craniofacial bone, which can cause patients to experience complications with their appearance and their ability to function. Regarding grafting procedures' complications and disadvantages, the newly emerging field of tissue regeneration has shown promise. Tissue -engineered technologies and their applications in the craniofacial region are increasingly gaining prominence with limited postoperative risk and cost. MSCs-derived exosomes are widely applied in bone tissue engineering to provide cell-free therapies since they not only do not cause immunological rejection in the same way that cells do, but they can also perform a cell-like role. Additionally, the hydrogel system is a family of multipurpose platforms made of cross-linked polymers with considerable water content, outstanding biocompatibility, and tunable physiochemical properties for the efficient delivery of commodities. Therefore, the promising exosome-loaded hydrogels can be designed for craniofacial bone regeneration. This review lists the packaging techniques for exosomes and hydrogel and discusses the development of a biocompatible hydrogel system and its potential for exosome continuous delivery for craniofacial bone healing.

Hierarchically porous surface of HA-sandblasted Ti implant screw using the plasma electrolytic oxidation: Physical characterization and biological responses.

The surface topological features of bioimplants are among the key indicators for bone tissue replacement because they directly affect cell morphology, adhesion, proliferation, and differentiation. In this study, we investigated the physical, electrochemical, and biological responses of sandblasted titanium (SB-Ti) surfaces with pore geometries fabricated using a plasma electrolytic oxidation (PEO) process. The PEO treatment was conducted at an applied voltage of 280 V in a solution bath consisting of 0.15 mol L-1 calcium acetate monohydrate and 0.02 mol L-1 calcium glycerophosphate for 3 min. The surface chemistry, wettability, mechanical properties and corrosion behavior of PEO-treated sandblasted Ti implants using hydroxyapatite particles (PEO-SB-Ti) were improved with the distribution of calcium phosphorous porous oxide layers, and showed a homogeneous and hierarchically porous surface with clusters of nanopores in a bath containing calcium acetate monohydrate and calcium glycerophosphate. To demonstrate the efficacy of PEO-SB-Ti, we investigated whether the implant affects biological responses. The proposed PEO-SB-Ti were evaluated with the aim of obtaining a multifunctional bone replacement model that could efficiently induce osteogenic differentiation as well as antibacterial activities. These physical and biological responses suggest that the PEO-SB-Ti may have a great potential for use an artificial bone replacement compared to that of the controls.

Osteogenic Potential of Magnesium Oxide Nanoparticles in Bone Regeneration: A Systematic Review.

Guided bone regeneration (GBR) plays a crucial role in the augmentation of alveolar bone, especially in cases of dental implants. The main principle behind using membranes in guided tissue regeneration (GTR) is to prevent epithelial downgrowth as well as connective tissue on the root surface. However, the membranes lack some major properties, such as osteogenic and antimicrobial properties. Magnesium (Mg) is one of the biodegradable materials that is gaining interest because of its favourable mechanical properties and biocompatibility. It also possesses pro-osteogenic properties and significant inhibition of biofilm formation and maturation. These features have attracted increasing interest in using magnesium oxide nanoparticles in GBR membrane applications. This systematic review assesses the osteogenic potential of magnesium oxide nanoparticles in periodontal bone regeneration. The literature search used PubMed, PubMed Central, Medline, and Cochrane databases to examine systematic reviews published till March 2023. Seven articles were included based on the selection criteria. We included all in vitro and in vivo clinical studies based on the osteogenic potential of magnesium oxide nanoparticles in periodontal bone regeneration. The seven studies provided evidence that magnesium oxide nanoparticles, when incorporated in any substrate, showed higher osteogenic potential in terms of higher alkaline phosphatase levels, bone volume fraction, and bone mineral density. The optimum concentration of magnesium oxide can be an ideal additive to various substrates to promote bone regeneration. Because most of the studies were conducted on calvarial defects, further studies should focus only on bone regeneration related to periodontal regeneration.

Multifunctional MXene-Based Platforms for Soft and Bone Tissue Regeneration and Engineering.

MXenes and their composites hold great promise in the field of soft and bone tissue regeneration and engineering (TRE). However, there are challenges that need to be overcome, such as ensuring biocompatibility and controlling the morphologies of MXene-based scaffolds. The future prospects of MXenes in TRE include enhancing biocompatibility through surface modifications, developing multifunctional constructs, and conducting in vivo studies for clinical translation. The purpose of this perspective about MXenes and their composites in soft and bone TRE is to critically evaluate their potential applications and contributions in this field. This perspective aims to provide a comprehensive analysis of the challenges, advantages, limitations, and future prospects associated with the use of MXenes and their composites for soft and bone TRE. By examining the existing literature and research, the review seeks to consolidate the current knowledge and highlight the key findings and advancements in MXene-based TRE. It aims to contribute to the understanding of MXenes' role in promoting soft and bone TRE, addressing the challenges faced in terms of biocompatibility, morphology control, and tissue interactions.

Platelet rich fibrin as a bioactive matrix with proosteogenic and proangiogenic properties on human healthy primary cells in vitro.

Blood concentrates like platelet rich fibrin (PRF) have been established as a potential autologous source of cells and growth factors with regenerative properties in the field of dentistry and regenerative medicine. To further analyze the effect of PRF on bone tissue regeneration, this study investigated the influence of liquid PRF matrices on human healthy primary osteoblasts (pOB) and co-cultures composed of pOB and human dermal vascular endothelial cells (HDMEC) as in vitro model for bone tissue regeneration. Special attention was paid to the PRF mediated influence on osteoblastic differentiation and angiogenesis. Based on the low-speed centrifugation concept, cells were treated indirectly with PRF prepared with a low (44 g) and high relative centrifugal force (710 g) before the PRF mediated effect on osteoblast proliferation and differentiation was assessed via gene and protein expression analyses and immunofluorescence. The results revealed a PRF-mediated positive effect on osteogenic proliferation and differentiation accompanied by increased concentration of osteogenic growth factors and upregulated expression of osteogenic differentiation factors. Furthermore, it could be shown that PRF treatment resulted in an increased formation of angiogenic structures in a bone tissue mimic co-culture of endothelial cells and osteoblasts induced by the PRF mediated increased release of proangiogenic growth factors. The effects on osteogenic proliferation, differentiation and vascularization were more evident when low RCF PRF was applied to the cells. In conclusion, PRF possess proosteogenic, potentially osteoconductive as well as proangiogenic properties, making it a beneficial tool for bone tissue regeneration.

What is the context?The treatment of bone defects is still a challenge in the field of regenerative medicine. In this context, researchers and clinicians are continuously focusing on developing new therapeutic strategies like the use of autologous blood concentrates like Platelet rich fibrin (PRF) to improve regeneration by directly delivering wound healing promoting cells and growth factors to the defect side in order to restore the structure and functional integrity of damaged hard tissue in combination with adequate tissue regeneration.What is new?Focus of the present in vitro study was to further evaluate the potential of PRF paying particular attention to the PRF-mediated effect on osteogenic differentiation and angiogenesis of human primary osteoblasts as well as on a more complex tissue like co-culture consisting of osteoblasts and microvascular endothelial cells. We could demonstrate that PRF is able to support and affect a variety of processes involved in bone tissue regeneration including osteogenic proliferation, osteogenic differentiation as well as angiogenic structure formation.Treatment of PRF resulted in:- increased cell viability*- higher expression of osteogenic differentiation factors*- higher release of osteogenic growth factors*- increased formation of microvessel-like structures*(*compared to untreated control)What is the impact?PRF represents a beneficial autologous tool for regenerative purposes combining proosteogenic and proangiogenic properties. Therefore, PRF might be used for applications in versatile fields of medicine in the context of improving bone tissue regeneration.

Preparation of PDA-GO/CS composite scaffold and its effects on the biological properties of human dental pulp stem cells.

Reduced graphene oxide (rGO) is an graphene oxide (GO) derivative of graphene, which has a large specific surface area and exhibited satisfactory physicochemical characteristics. In this experiment, GO was reduced by PDA to generate PDA-GO complex, and then PDA-GO was combined with Chitosan (CS) to synthesize PDA-GO/CS composite scaffold. PDA-GO was added to CS to improve the degradation rate of CS, and it was hoped that PDA-GO/CS composite scaffolds could be used in bone tissue engineering. Physicochemical and antimicrobial properties of the different composite scaffolds were examined to find the optimal mass fraction. Besides, we examined the scaffold's biocompatibility by Phalloidin staining and Live and Dead fluorescent staining.Finally, we applied ALP staining, RT-qPCR, and Alizarin red S staining to detect the effect of PDA-GO/CS on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). The results showed that PDA-GO composite was successfully prepared and PDA-GO/CS composite scaffold was synthesized by combining PDA-GO with CS. Among them, 0.3%PDA-GO/CS scaffolds improves the antibacterial activity and hydrophilicity of CS, while reducing the degradation rate. In vitro, PDA-GO/CS has superior biocompatibility and enhances the early proliferation, migration and osteogenic differentiation of hDPSCs. In conclusion, PDA-GO/CS is a new scaffold materialsuitable for cell culture and has promising application prospect as scaffold for bone tissue engineering.

In Vitro Studies on 3D-Printed PLA/HA/GNP Structures for Bone Tissue Regeneration.

The successful regeneration of large-size bone defects remains one of the most critical challenges faced in orthopaedics. Recently, 3D printing technology has been widely used to fabricate reliable, reproducible and economically affordable scaffolds with specifically designed shapes and porosity, capable of providing sufficient biomimetic cues for a desired cellular behaviour. Natural or synthetic polymers reinforced with active bioceramics and/or graphene derivatives have demonstrated adequate mechanical properties and a proper cellular response, attracting the attention of researchers in the bone regeneration field. In the present work, 3D-printed graphene nanoplatelet (GNP)-reinforced polylactic acid (PLA)/hydroxyapatite (HA) composite scaffolds were fabricated using the fused deposition modelling (FDM) technique. The in vitro response of the MC3T3-E1 pre-osteoblasts and RAW 264.7 macrophages revealed that these newly designed scaffolds exhibited various survival rates and a sustained proliferation. Moreover, as expected, the addition of HA into the PLA matrix contributed to mimicking a bone extracellular matrix, leading to positive effects on the pre-osteoblast osteogenic differentiation. In addition, a limited inflammatory response was also observed. Overall, the results suggest the great potential of the newly developed 3D-printed composite materials as suitable candidates for bone tissue engineering applications.

In situ forming alginate/gelatin hydrogel scaffold through Schiff base reaction embedded with curcumin-loaded chitosan microspheres for bone tissue regeneration.

In this study, we developed a biocompatible composite hydrogel that incorporates microspheres. This was achieved using a Schiff base reaction, which combines the amino and aldehyde groups present in gelatin (Gel) and oxidized alginate (OAlg). We suggest this hydrogel as a promising scaffold for bone tissue regeneration. To further boost its osteogenic capabilities and mechanical resilience, we synthesized curcumin (Cur)-loaded chitosan microspheres (CMs) and integrated them into the Gel-OAlg matrix. This formed a robust composite gel framework. We conducted comprehensive evaluations of various properties, including gelation time, morphology, compressive strength, rheological behavior, texture, swelling rate, in vitro degradation, and release patterns. A remarkable observation was that the inclusion of 30 mg/mL Cur-CMs significantly enhanced the hydrogel's mechanical and bioactive features. Over three weeks, the Gel-OAlg/Cur-CMs (30) composite showed a cumulative curcumin release of 35.57%. This was notably lower than that observed in standalone CMs and Gel-OAlg hydrogels. Additionally, the Gel-OAlg/Cur-CMs (30) hydrogel presented a reduced swelling rate and weight loss relative to hydrogels devoid of Cur-CMs. On the cellular front, the Gel-OAlg/Cur-CMs (30) hydrogel showcased superior biocompatibility. It also displayed increased calcium deposition, alkaline phosphatase (ALP) activity, and elevated osteogenic gene expression in human bone marrow mesenchymal stem cells (hBMSCs). These results solidify its potential as a scaffold for bone tissue regeneration.

Ultrasound-triggered biomimetic ultrashort peptide nanofiber hydrogels promote bone regeneration by modulating macrophage and the osteogenic immune microenvironment.

The immune microenvironment plays a vital role in bone defect repair. To create an immune microenvironment that promotes osteogenesis, researchers are exploring ways to enhance the differentiation of M2-type macrophages. Functional peptides have been discovered to effectively improve this process, but they are limited by low efficiency and rapid degradation in vivo. To overcome these issues, peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel. These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation, activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle, inhibiting reactive oxygen species production and enhancing M2 macrophage polarization. The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I, accelerating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. Thus, modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.