Composite Scaffolds Research Articles

Enhancing the mechanical performance of 3D-printed self-hardening calcium phosphate bone scaffolds: PLGA-based strategies

Over the last decade, 3D-printed porous calcium phosphates have emerged in the market for customized bone reconstruction. However, despite their excellent biological properties, the inherent brittleness is an obstacle that limits their clinical applications, as the scaffolds must withstand the surgical procedures and the mechanical stresses once implanted. Low-temperature self-hardening calcium phosphate inks offer unique possibilities to be reinforced with polymers, as they do not require high-temperature treatments. This study compares two routes for incorporating poly (lactic-co-glycolic acid) (PLGA) into 3D-printed calcium phosphate scaffolds: i) the use of a PLGA solution as a binder in an alpha-tricalcium phosphate self-hardening ink; ii) the infiltration of a PLGA solution into previously hardened 3D-printed calcium-deficient hydroxyapatite scaffolds. The influence of the added PLGA on the physical-chemical properties, mechanical performance and in vitro biological properties is assessed using a commercially available biomimetic calcium phosphate scaffold as a control. The addition of PLGA increases the plastic deformation capacity and the strength, both in compression and bending, and significantly improves the work of fracture of the scaffolds, up to an 8-fold in compression when PLGA is incorporated as a binder in the ink. Moreover, screwability tests demonstrate the enhanced fixability of the composite scaffolds in a knife-edge ridge indication with challenging fixation in the jaw. Importantly, the improvement of the mechanical properties by the addition of PLGA does not impair the good cytocompatibility of the material. Regarding the two routes studied, the PLGA incorporation in the ink is the best option in terms of overall improvement of the mechanical performance and osteogenic cell response.

Osteogenic potentials in canine mesenchymal stem cells: unraveling the efficacy of polycaprolactone/hydroxyapatite scaffolds in veterinary bone regeneration

BackgroundThe integration of stem cells, signaling molecules, and biomaterial scaffolds is fundamental for the successful engineering of functional bone tissue. Currently, the development of composite scaffolds has emerged as an attractive approach to meet the criteria of ideal scaffolds utilized in bone tissue engineering (BTE) for facilitating bone regeneration in bone defects. Recently, the incorporation of polycaprolactone (PCL) with hydroxyapatite (HA) has been developed as one of the suitable substitutes for BTE applications owing to their promising osteogenic properties. In this study, a three-dimensional (3D) scaffold composed of PCL integrated with HA (PCL/HA) was prepared and assessed for its ability to support osteogenesis in vitro. Furthermore, this scaffold was evaluated explicitly for its efficacy in promoting the proliferation and osteogenic differentiation of canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) to fill the knowledge gap regarding the use of composite scaffolds for BTE in the veterinary orthopedics field.ResultsOur findings indicate that the PCL/HA scaffolds substantially supported the proliferation of cBM-MSCs. Notably, the group subjected to osteogenic induction exhibited a markedly upregulated expression of the osteogenic gene osterix (OSX) compared to the control group. Additionally, the construction of 3D scaffold constructs with differentiated cells and an extracellular matrix (ECM) was successfully imaged using scanning electron microscopy. Elemental analysis using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy confirmed that these constructs possessed the mineral content of bone-like compositions, particularly the presence of calcium and phosphorus.ConclusionsThis research highlights the synergistic potential of PCL/HA scaffolds in concert with cBM-MSCs, presenting a multidisciplinary approach to scaffold fabrication that effectively regulates cell proliferation and osteogenic differentiation. Future in vivo studies focusing on the repair and regeneration of bone defects are warranted to further explore the regenerative capacity of these constructs, with the ultimate goal of assessing their potential in veterinary clinical applications.

Injectable dual drug-loaded thermosensitive liposome-hydrogel composite scaffold for vascularised and innervated bone regeneration

Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.

NIR-Responsive Deployable and Self-Fitting 4D-Printed Bone Tissue Scaffold.

The treatment of irregular-shaped and critical-sized bone defects poses a clinical challenge. Deployable, self-fitting tissue scaffolds that can be implanted by minimally invasive procedures are a promising solution. Toward this, we fabricated NIR-responsive and programmable polylactide-co-trimethylene carbonate (PLMC) scaffolds nanoengineered with polydopamine nanoparticles (PDA) by extrusion-based three-dimensional (3D) printing. The 3D-printed scaffolds demonstrated excellent (>99%), fast (under 30 s), and tunable shape recovery under NIR irradiation. PLMC-PDA composites demonstrated significantly higher osteogenic potential in vitro as revealed by the significantly enhanced alkaline phosphatase (ALP) secretion and mineral deposition in contrast to neat PLMC. Intraoperative deployability and in vivo bone regeneration ability of PLMC-PDA composites were demonstrated, using self-fitting scaffolds in critical-sized cranial bone defects in rabbits. The 3D-printed scaffolds were deformed into compact shapes that could self-fit into the defect shape intraoperatively under low power intensity (0.76 W cm-2) NIR. At 6 and 12 weeks postsurgical implantation, near-complete bone regeneration was observed in PLMC-PDA composites, unlike neat PLMC through microcomputed tomography (micro-CT) analysis. The potential clinical utility of the 3D-printed composites to secure complex defects was confirmed through self-fitting of the scaffolds into irregular defects in ex vivo models of rabbit tibia, mandible, and tooth models. Taken together, the composite scaffolds fabricated here offer an innovative strategy for minimally invasive deployment to fit irregular and complex tissue defects for bone tissue regeneration.

3D chitosan scaffolds loaded with ZnO nanoparticles for bone tissue engineering

Bone defect has always been a difficult problem in clinical work. According to the current research results, tissue engineered scaffolds with a single function, structure, and composition are not sufficient to repair complex bone defects. In this work, a three-dimensional (3D) chitosan degradable composite scaffold loaded with zinc oxide (ZnO) was constructed, and the effect of ZnO content on scaffold performance and osteogenesis was explored. The 3D composite scaffold was prepared by freeze-drying technology. The microstructure, porosity, degradation performance, release performance, swelling performance, cytotoxicity, cell adhesion and osteogenic ability of ZnO nanoparticles and chitosan (ZnONPs/CS) composite scaffolds were measured. The results show that an appropriate amount of ZnO may be helpful to regulate the stability and degradation characteristics of the scaffold to a certain extent. Moreover, the composite scaffold could release ZnO into the simulated body fluid environment. The appropriate amount of ZnO helps to promote the proliferation, adhesion, and osteogenic differentiation of MC3T3-E1 cells. At a ZnO content of 3wt%, both in vitro and vivo results showed relatively optimal biocompatibility and bioactivity of the scaffolds. This work could at least provide some positive insights for the selection of ZnO dosage, construction of chitosan-based 3D scaffolds, tissue engineering applications, and clinical treatment.

Study on performance regulation of electro-mechanical properties 3D printed BaTiO3/HA porous structure composite ceramic

BaTiO3/Ca10(PO4)6(OH)2 composite ceramic is an outstanding representative of piezoelectric biomaterials, with excellent biocompatibility and piezoelectric effect, and has potential applications in the field of bone tissue repair. In this work, vat photopolymerization 3D printing technology was used to fabricate triply periodic minimal surface structure BaTiO3/Ca10(PO4)6(OH)2 composite ceramic bone tissue scaffolds with different pore sizes and porosity, and their mechanical and electrical properties were studied. First, the ceramic slurry configuration process was optimized to obtain a ceramic slurry with high solid content (45 vol%) and excellent rheological properties. Then the effect of sintering temperature on microstructure, relative density, mechanical properties, and electrical properties is discussed. The results show that when sintering at 1300 °C, the BaTiO3/Ca10(PO4)6(OH)2 composite ceramic has the highest relative density (99.18 %), the highest compressive strength (44 MPa), large relative dielectric constant (379–389), and low dielectric loss. The polarization electric field strength of the BaTiO3/Ca10(PO4)6(OH)2 composite ceramic was set to 15 kV/cm through the test of the hysteresis loop. Finally, based on multi-physics coupled finite element simulation, the effects of different porosity and different pore sizes on stress distribution and piezoelectric potential were analyzed, and the relationship between them was explored through experiments. The results show that as the porosity increases and the pore size decreases, the mechanical properties of the scaffold decrease significantly, and its compressive strength ranges between 1.67 and 4.26 MPa; as the porosity increases and the pore size increases, the piezoelectric coefficient (d33) of the scaffold showed a decreasing trend, and its d33 ranged between 2 and 9 pC/N. The mechanical and electrical properties of the scaffold meet the performance requirements of cancellous bone. In summary, this work provides a strategy for the application of customized BaTiO3/Ca10(PO4)6(OH)2 composite ceramic scaffolds in new-generation orthopedic implants.

Polycaprolactone strengthening gelatin/nano-hydroxyapatite composite biomaterial inks for potential application in extrusion-based 3D printing bone scaffolds

Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the printability of the ink, the optimal conditions were identified: a n-HA concentration of 50% (w/w), a printing temperature of 10–15 ℃, a printing pressure of 2.5 bar, and a printing speed of 7 mm/s. The resulting biomaterial inks, with a composition of 25% Gel, 25% PCL, and 50% n-HA, demonstrated excellent printability and stability, along with significantly enhanced mechanical properties. As a result, 3D scaffolds with high printability and shape fidelity can be printed at room temperature, followed by deep freezing at -80 ℃ and cross-linking with vanillin. The Gel-based composite scaffolds demonstrated excellent biocompatibility, cell adhesion, cell viability and nano-hydroxyapatite absorption in vitro. Additionally, in vivo experiments revealed that the bioactive scaffold biodegraded during implantation and significantly promoted bone regeneration at the defect site. This provides a promising strategy for treating bone defects in clinical setting. In conclusion, the Gel/PCL/n-HA biomaterial inks presented here offer an innovative solution for extrusion bioprinting in the field of bone tissue engineering.Graphical

Microporous polylactic acid/chitin nanocrystals composite scaffolds using in-situ foaming 3D printing for bone tissue engineering

Bone injury represents an urgent clinical problem, and implantable bioscaffolds offer suitable means for replacing and regenerating damaged tissues. This paper proposes an in-situ foaming printing method employing material extrusion additive manufacturing technology and physical foaming to prepared poly(lactic acid)/chitin nanocrystals (CHNCs) microporous composite scaffolds, featuring pore sizes ranging from 9 ± 5 μm. This method offers a novel strategy for the preparation of poly(lactic acid)-based scaffolds with good biocompatibility. Material characterization and mechanical property testing demonstrated that the in-situ foaming printed PLA scaffolds exhibited excellent foam printability, and the expansion ratio and compression properties of the scaffolds could be adjusted by modifying the CHNCs concentration and the printing speed, achieving a compression modulus between 39.2 MPa and 54.3 MPa. Furthermore, at equivalent foaming multiplicity (1.5–2.6 times), the compression modulus increased by nearly 100 % compared to previously reported PLA-based foam scaffolds. Importantly, the PLA/CHNCs scaffolds produced via in-situ foaming exhibited superior biocompatibility compared to directly printed PLA scaffolds. This PLA/CHNCs composite scaffold provides a promising approach to addressing and repairing bone defects.

Scaffold loaded LPS-hUCMSC-sEVs promote Osteo/odontogenic differentiation and angiogenic potential of hDPSCs

ObjectiveThe formation of dentin-pulp complex determines the success of vital pulp therapy. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUCMSC-sEVs) appeared to have stronger effect in anti-inflammatory and promoting the proliferation and migration of human dental pulp stem cells (hDPSCs). Moreover, Lipopolysaccharides (LPS) pretreatment can enhance the rapeutic potency of extracellular vesicles. LPS pretreatment hUCMSC-sEVs have the potential to regenerate the dentin-pulp complex by recruiting hDPSCs. This paper aims to develop collagen sponge/self-assembling peptide nanofiber scaffold (CS/SAPNS) composite scaffold loaded with LPS pretreatment hUCMSC-sEVs (CS/SAPNS-sEVs), and assess the release characteristics of hUCMSC-sEVs and the effect of this composite scaffold on osteo/odontogenic differentiation and angiogenic potential in hDPSCs. MethodsLPS pretreatment hUCMSC-sEVs (LPS-hUCMSC-sEVs) were mixed with self-assembling peptide hydrogel and loaded onto collagen sponge to obtain the CS/SAPNS-sEVs. BCA assay, nanoparticle analysis, transmission electron microscopy and laser confocal microscopy were used to investigate the characteristics of LPS-hUCMSC-sEVs loaded on CS/SAPNS. Osteo/odontogenic differentiation ability of hDPSCs were analyzed by ALP stainning, alizarin red staining. RT-PCR and Western blot analysis were performed to confirm the levels of osteo/odontogenic factors and angiogenic factors, and the involvement of NF-κB pathway was verified by immunocytochemical staining and Western blot analysis. ResultsCS/SAPNS could control LPS-hUCMSC-sEVs release for 7 days and keep their structural integrity. CS/SAPNS-sEVs promoted deposition of calcified nodules and expression of osteogenic/odontogenic and angiogenic factors in hDPSCs. On the contrary, inhibition of the NF-κB pathway down-regulated the expression of CS/SAPNS-sEVs-regulated osteo/odontogenic and angiogenic factors. ConclusionCS/SNAPS could be used as scaffold for LPS-hUCMSC-sEVs, and CS/SAPNS-sEVs may promote osteo/odontogenic differentiation and enhance the angiogenic potential of hDPSCs through activating the NF-κB pathway.

The preventive effect of photocrosslinked Hep/GelMA hydrogel loaded with PRF on MRONJ.

Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.

Multimaterial additive manufacturing of poly-L-lactic acid– hydroxylapatite/graphene oxide scaffold fabricated via vat photopolymerization: experimental investigation, analysis and cell study

PurposeThis study aims to design and implement a multimaterial system for printing multifunctional specimens suitable for various sectors, with a particular focus on biomedical applications such as addressing mandibular bone loss.Design/methodology/approachTo enhance both the mechanical and biological properties of scaffolds, an automatic multimaterial setup using vat photopolymerization was developed. This setup features a linear system with two resin vats and one ultrasonic cleaning tank, facilitating the integration of diverse materials and structures to optimize scaffold composition. Such versatility allows for the simultaneous achievement of various characteristics in scaffold design.FindingsThe printed multimaterial scaffolds, featuring 20 Wt.% hydroxylapatite (HA) on the interior and poly-L-lactic acid (PLLA) with 1 Wt.% graphene oxide (GO) on the exterior, exhibited favorable mechanical and biological properties at the optimum postcuring and heat-treatment time. Using an edited triply periodic minimal surface (TPMS) lattice structure further enhanced these properties. Various multimaterial specimens were successfully printed and evaluated, showcasing the capability of the setup to ensure functionality, cleanliness and adequate interface bonding. Additionally, a novel Gyroid TPMS scaffold with a nominal porosity of 50% was developed and experimentally validated.Originality/valueThis study demonstrates the successful fabrication of multimaterial components with minimal contaminations and suitable mechanical and biological properties. By combining PLLA-HA and PLLA-GO, this innovative technique holds significant promise for enhancing the effectiveness of regenerative procedures, particularly in the realm of dentistry.

Synergistic effect of waste-derived β-tricalcium phosphate microbeads loaded in hydroxyapatite-keratin-polyvinyl alcohol composite matrix in drug release for osteosarcoma treatment

BackgroundSustained drug delivery system (DDS) for clinically relevant osteosarcoma medications is a promising strategy for treatment. β-tricalcium phosphate (β-TCP) microbeads loaded with doxorubicin hydrochloride (DOX) and cis-diamminedichloroplatin (CDDP) anticancer drugs in a matrix of hydroxyapatite-keratin-polyvinyl alcohol composite matrix scaffolds (HAp-K-PVA) was developed as promising DDS. HAp, β-TCP, and K utilized for the development of DDS were resourced from avian eggshells and human hairs, respectively, and duly characterized before application.MethodsThe β-TCP/alginate microbeads were fabricated using droplet extrusion and ionotropic gelation, and integrated into secondary drug carrier HAp-K-PVA composite matrix, via freeze gelation. The physicochemical and thermal characterization of developed microbeads and matrix scaffolds was performed.ResultsWhen DOX and CDDP were co-loaded in DDS, a synergistic impact was observed after 30 days of continuous release, in contrast to the immediate outburst as seen with individual DOX and CDDP releases. Besides, the drug release from the microbeads only, the release with the HAp-K-PVA composite matrix scaffolds was observed slower. The controlled release, antibacterial effectiveness against the test pathogens and cell viability with osteoblast-like osteosarcoma (UTOS) cells indicated the therapeutic potential for the treatment of osteosarcoma in situ. The cell viability was observed for 24 h, which showed nearly 90% after 24 h for HAp-K-PVA composite matrix scaffolds, decreased for all the scaffold groups after 72 h, indicating the enhancement due to combined synergistic effect of the co-loaded drugs.ConclusionThis study established a promising foundation for novel and sustainable biomaterials for osteosarcoma treatment. Further advancement holds the potential to enhance patient clinical outcomes and foster advancements in the field of regenerative medicine.

Abalone shells bioenhanced carboxymethyl chitosan/collagen/PLGA bionic hybrid scaffolds achieving biomineralization and osteogenesis for bone regeneration

Inspired by the formation of natural abalone shells (AS) similar to calcium salt deposition in human orthodontics, AS is used as an emulsifier in the scaffold to solve the problem of coexistence of natural and synthetic polymers and promote new bone formation. In this study, AS-stabilized and reinforced carboxymethyl chitosan/collagen/PLGA porous bionic composite scaffolds (AS/CMCS/Col/PLGA) were fabricated through the emulsion polymerization and bionic hybrid technology. As the addition of AS increased from 0.75 to 3.0 wt%, homogeneous distribution of flower-like particles could be observed on the inner surface of the scaffold, and its mechanical properties were improved. Particularly, 3.0 wt% AS-doped scaffolds (S3 and C + S3) exhibited excellent inorganic mineral deposition and osteoblast proliferation and differentiation abilities in vitro. In a SD rat calvarial defect model, they effectively promoted new bone formation in the defect and accelerated expression of osteogenic-angiogenic related proteins (COLI, OCN, VEGF). By virtue of its combined merits including good mechanical properties, inducing mineralization crystallization and facilitating osteogenesis, the 3.0 wt% AS-doped scaffold promises to be employed as a novel bone repair material for bone tissue regeneration.

Investigate the in vitro biocompatibility, biodegradation, cytotoxicity, and differentiation potential of 3-D gelatin-nanocellulose composite scaffolds loaded with nanohydroxyapatite and simvastatin

Bone tissue engineering has been proposed as a promising solution for healing of bone fractures. An important aspect of bone tissue engineering is the implantable scaffolds that participate in the regeneration and repair of bone tissue. In this study, the composite scaffolds of gelatin- nanocellulose loaded with nanohydroxyapatite and simvastatin (as the osteoinductive component) were fabricated using freeze- drying method. Scaffolds were characterized in terms of morphology, mechanical, biodegradability, water absorption capacity, and simvastatin release characteristics. Also, the biocompatibility and differentiation potential of the scaffolds were evaluated on human bone marrow-derived mesenchymal stem cells using the MTT assay and alizarin red staining, respectively. The simvastatin loaded scaffolds showed a sustained release profile in vitro up to 216 h. The results of BMSCs differentiation by alizarin red staining showed significant differences between the simvastatin loaded group and other groups. Moreover, the results of MTT assay verified cytocompatibility and non-toxicity of the scaffolds. Therefore, the gelatin-nano cellulose composite scaffolds loaded with hydroxyapatite and simvastatin may be considered promising for use in bone tissue engineering.

Polyacrylonitrile‒Chitosan IPN composite scaffolds that closely mimic the human trabecular bone structure for tissue engineering

Successful bone tissue engineering involves managing several important parameters, such as the design of intercommunicating porous structures, pore sizes, and the material and mechanical suitability of the material. In our work, we focused on the preparation of a synthetic scaffold that morphologically mimics the structure of human trabecular bone. The scaffolds were fabricated through the thermal modification (TM) of polyacrylonitrile. The scaffold strength was supported by a crosslinked chitosan supporting network. The prepared scaffold has imprinted pores of the appropriate size to facilitate the ingrowth and proliferation of human osteoblasts throughout the entire pore volume created by a primary porogen, sodium chloride. The resulting material has a dual porous morphological structure, in which adjustable larger pores support cellular ingrowth into the scaffold, whereas smaller pores, created using succinonitrile (SCN) as a secondary porogen, increase the diffusion of oxygen and nutrients to developing cells. The mechanical properties of the scaffold were promoted by the use of a secondary interpenetrating network (IPN) based on chitosan. The incorporation of secondary IPNs led to a significant improvement in the mechanical characteristics of the scaffold. Two crosslinking agents were used: the widely utilized glutaraldehyde (GA) and its green, nontoxic alternative, genipin (GEN).The current study introduces a synthetic scaffold that effectively mimics the structure of human trabecular bone, providing a conducive environment for osteoblast proliferation and ingrowth. We incorporated a dual porous morphology and a secondary IPN based on chitosan and found that the scaffold exhibited improved mechanical properties and nutrient diffusion capabilities. This research highlights the potential of these scaffolds for major advancements in bone tissue engineering, demonstrating their noncytotoxic nature and ability to support the adhesion and proliferation of the human osteosarcoma cell line SAOS-2. The described scaffold preparation technique may offer distinct advantages over current high-end methods such as 3D printing. The primary benefit lies in its very simple instrumentation, which enables the creation of a complex trabecular bone morphology with both macro- and microporosity in the bulk, which is still challenging for common 3D printers. Additionally, IPN with chitosan can be postmodified, substantially expanding the potential applications of these scaffolds.

Polycaprolactone in Bone Tissue Engineering: A Comprehensive Review of Innovations in Scaffold Fabrication and Surface Modifications.

Bone tissue engineering has seen significant advancements with innovative scaffold fabrication techniques such as 3D printing. This review focuses on enhancing polycaprolactone (PCL) scaffold properties through structural modifications, including surface treatments, pore architecture adjustments, and the incorporation of biomaterials like hydroxyapatite (HA). These modifications aim to improve scaffold conformation, cellular behavior, and mechanical performance, with particular emphasis on the role of mesenchymal stem cells (MSCs) in bone regeneration. The review also explores the potential of integrating nanomaterials and graphene oxide (GO) to further enhance the mechanical and biological properties of PCL scaffolds. Future directions involve optimizing scaffold structures and compositions for improved bone tissue regeneration outcomes.

Biomimetic fiber/hydrogel composite scaffolds based on chitosan hydrogel and surface modified PCL chopped-microfibers

Hydrogel/fiber composites have received wide attention as tissue engineering scaffolds due to the outstanding properties of fibers and hydrogels. In the current research, a hydrogel/fiber composite scaffold was made based on chitosan-modified polycaprolactone (PCL) microfibers and chitosan hydrogel as a binder. The presence of chitosan as a modifier on the surface of fibers and as a binder between fibers can create scaffolds with excellent structural and mechanical properties. To this end, the three-dimensional microfibers were first functionalized with amine groups. Then, the chitosan chains were attached to the fibers by an aldehyde coupling agent and Schiff base reaction. FTIR and Raman spectroscopies corroborated that chitosan was successfully immobilized on PCL fibers. Chitosan-modified fibers were molded with chitosan solutions of various concentrations and the prepared composite scaffolds were stabilized using ionic crosslinking. The obtained composites represented a porous 3D structure with highly interconnected pores. The compressive modulus increased by 19 and 2.7 folds and the tensile modulus was augmented by 28 and 4 folds, in respective dry and swollen states with increasing hydrogel concentration from 0.1 to 1 %. Hydrogel/fiber composites were able to preserve cell viability, and increasing the hydrogel proportion increased adhesion, proliferation and penetration of cells into the scaffold.

Targeting Bacteria-Induced Ferroptosis of Bone Marrow Mesenchymal Stem Cells to Promote the Repair of Infected Bone Defects.

The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.

3D-bioprinted poly(lactic acid)/β-TCP/mesoporous silica scaffolds: An investigation on in-vitro bioactivity and osteogenesis characteristics

The current work aims to formulate novel bioactive and biocompatible 3D printed poly (l-lactic acid)/Beta tri calcium phosphate composite scaffolds reinforced with different types of mesoporous silica materials [PLA/β-TCP/MSMs] for bone regeneration application, which is not envisaged earlier. The bioink encompassing 30 % organic content (PLA) and 70 % inorganic content (β-TCP and MSMs) is formulated and their rheological characteristics are evaluated. Optimization of process conditions for 3D printed PLA composite scaffolds was done and pneumatic extrusion is performed. The physico-chemical properties as well as in vitro biological characteristics were assessed for 3D printed PLA/β-TCP/MSMs based composite scaffolds. The existence of β-TCP and MSMs incorporated into PLA matrix was observed to fasten the formation of hydroxyapatite, as evidenced by in vitro bioactivity assessment. The in vitro cytocompatibility analysis revealed that the 3D printed PLA/β-TCP/MSMs composite scaffolds exhibit suitable biocompatible behaviour and osteogenic potential. The calcium mineralization and ALP expression were also noticed in higher levels for 3D printed PLA/β-TCP/MSMs composite scaffolds. Gene expression analysis confirmed the expression of COL1, OCN, BMP-2 and RUNX2 on 3D printed PLA/β-TCP/MSMs composite scaffolds. The results speculate that this novel formulation closely resembling the composition of natural bone might have promising applications in terms of in vivo bone tissue engineering.

Adapting to the acidic environment of the NP: RADA16-PLGA (TGF-β3) induces chondrogenic differentiation of BMSCs.

Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-β3 and explored their ability for chondrogenic differentiation in vitro.Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining.Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-β3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes.Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process.