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Articular cartilage injury impairs joint function and necessitates orthopedic intervention to restore the structure and function of the cartilage. Extracellular matrix (ECM) scaffolds derived from bone marrow mesenchymal stem cells (BMSCs) can effectively promote cell adhesion, proliferation, and chondrogenesis. However, pre-shaped ECM scaffolds have limited applicability due to their poor fit with the irregular surface of most articular cartilage defects. In this study, we fabricated an injectable active ECM hydrogel from autologous BMSCs-derived ECM by freeze-drying, liquid nitrogen milling, and enzymatic digestion. Moreover, our in vitro and in vivo results demonstrated that the prepared hydrogel enhanced chondrocyte adhesion and proliferation, chondrogenesis, cartilage regeneration, and integration with host tissue, respectively. These findings indicate that active ECM components can provide trophic support for cell proliferation and differentiation, restoring the structure and function of damaged cartilage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Biomimetic materials with complicated structures inspired by natural plants play a critical role in tissue engineering. The succulent plants, with complicated morphologies, show tenacious vitality in extreme conditions due to the physiological functions endowed by their unique anatomical structures. Herein, inspired by the macroscopic structure of succulent plants, succulent plant-like bioceramic scaffolds were fabricated via digital laser processing 3D printing of MgSiO 3 . Compared with conventional scaffolds with interlaced columns, the structures could prevent cells from leaking from the scaffolds and enhance cell adhesion. The scaffold morphology could be well regulated by changing leaf sizes, shapes, and interlacing methods. The succulent plant-like scaffolds show excellent properties for cell loading as well as cell distribution, promoting cellular interplay, and further enhancing the osteogenic differentiation of bone marrow stem cells. The in vivo study further illustrated that the succulent plant-like scaffolds could accelerate bone regeneration by inducing the formation of new bone tissues. The study suggests that the obtained succulent plant-like scaffold featuring the plant macroscopic structure is a promising biomaterial for regulating cell distribution, enhancing cellular interactions, and further improving bone regeneration.

Osteochondral defect (OCD) regeneration remains a great challenge. Recently, multilayer scaffold simulating native osteochondral structures have aroused broad interest in osteochondral tissue engineering. Here, we developed a 3D multifunctional bi-layer scaffold composed of a kartogenin (KGN)-loaded GelMA hydrogel (GelMA/KGN) as an upper layer mimicking a cartilage-specific extracellular matrix and a hydroxyapatite (HA)-coated 3D printed polycaprolactone porous scaffold (PCL/HA) as a lower layer simulating subchondral bone. The bi-layer scaffolds were subsequently modified with tannic acid (TA) prime-coating and E7 peptide conjugation (PCL/HA-GelMA/KGN@TA/E7) to regulate endogenous stem cell behaviors and exert antioxidant activity for enhanced osteochondral regeneration. In vitro , the scaffolds could support cell attachment and proliferation, and enhance the chondrogenic and osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs) in a specific layer. Besides, the incorporation of TA/E7 significantly increased the biological activity of the bi-layer scaffolds including the pro-migratory effect, antioxidant activity, and the maintenance of cell viability against oxidative stress. In vivo , the developed bi-layer scaffolds enhanced the simultaneous regeneration of cartilage and subchondral bone when implanted into a rabbit OCD model through macroscopic, micro-CT, and histological evaluation. Taken together, these investigations demonstrated that the 3D multifunctional bi-layer scaffolds could provide a suitable microenvironment for endogenous stem cells, and promote in situ osteochondral regeneration, showing great potential for the clinical treatment of OCD.

Segmental bone defects over the self-healing threshold are a major challenge for orthopedics. Despite the advancements in clinical practice, traditional tissue engineering methods are limited by the addition of heterogeneous cells and cytokines, leading to carcinoma or other adverse effects. Here, we present a cell-free and cytokine-free strategy using an ECM-mimetic self-assembling peptide hydrogel (SAPH)- polycaprolactone (PCL) composite scaffold. The hydrophilic SAPH endows the rigid PCL scaffold with excellent biocompatibility and preference for osteogenesis induction. The autologous cells around the bone defect site immediately grew, proliferated, and secreted ECM and cytokines after contacting the implanted SAPH-PCL composite scaffold, and the bone repair of rabbit ulnar segmental bone defect was achieved in just six months. Quantitative proteomic analysis reveals that the SAPH-PCL composite scaffold accelerates osteoblastogenesis, osteoclastogenesis, and angiogenesis with moderate immune responses and negligible effects on pathological fibrosis. These findings have important implications for the potential clinical applications of the SAPH-PCL composite scaffold in patients with segmental bone defects and identify the mechanisms of action for accelerated segmental bone defect repair.

It is of significance to construct the immunomodulatory and osteogenic microenvironment for three dimension (3D) regeneration of bone tissues. 3D scaffolds, with various chemical composition, macroporous structure and surface characteristics offer a beneficial microenvironment for bone tissue regeneration. However, there is a gap between the well-ordered surface microstructure of bioceramic scaffolds and immune microenvironment for bone regeneration. In this study, a gear-inspired 3D scaffold with well-ordered surface microstructure was successfully prepared through a modified extrusion-based 3D printing strategy for immunomodulation and bone regeneration. The prepared gear-inspired scaffolds could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. The subsequent in vivo study demonstrated that the gear-inspired scaffolds were able to attenuate inflammation and further promote new bone formation. The study develops a facile strategy to construct well-ordered surface microstructure which plays a key role in 3D immunomodulatory and osteogenic microenvironment for bone tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

3D-printed scaffolds have been developed as potential therapeutic strategies in bone tissue engineering. Mg/PCL biomaterials have been attracted much attention owing to biocompatibility, biodegradability as well as tunable mechanical properties. In this work, we developed 3D-printed customized Mg/PCL composite scaffolds with enhanced osteogenesis and biomineralization. Mg microparticles embedded in PCL-based scaffolds took a positive role in the improvement of biocompatibility, biomineralization, and biodegradable abilities. When incorporated with 3 wt% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that 3 Mg/PCL scaffolds had improved mechanical properties, good biocompatibility, enhanced osteogenic and angiogenic activities. Besides, the in vivo studies demonstrated that Mg/PCL scaffolds promoted tissue ingrowth and new bone formation. In sum, these findings indicated that 3D-printed cell-free Mg/PCL scaffolds are promising strategies for bone healing application., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of this study is to fabricate and test a 3D-printed PCL scaffold incorporating IGF-1-releasing PLGA nanoparticles for cartilage tissue engineering. IGF-1 loaded PLGA nanoparticles were produced by the double-emulsion method, and were incorporated onto 3D printed PCL scaffolds via PDA. Particle size, loading effciency (LE) and encapsulation effciency (EE) of the nanoparticles were examined. SEM, pore size, porosity, compression testing, contact angle, IGF-1 release kinetics of the composite scaffolds were also determined. For cell culture studies, CCK-8, Live/dead, MTT, GAG content and expression level of chondrocytes specific proteins and genes and HIF-1α were also tested. There was no difference of the nanoparticle size. And the LE and EE of IGF-1 in PLGA nanoparticles was about 5.53 ± 0.12% and 61.26 ± 2.71%, respectively. There was a slower, sustained release for all drug-loaded nanoparticles PLGA/PDA/PCL scaffolds. There was no difference of pore size, porosity, compressive strength of each scaffold. The contact angles PCL scaffolds were significant decreased when coated with PDA and PLGA nanoparticales. ( p  < .05) Live/dead staining showed more cells attached to the IGF-1 PLGA/PDA/PCL scaffolds. The CCK-8 and MTT assay showed higher cell proliferation and better biocompatibility of the IGF-1 PLGA/PDA/PCL scaffolds. ( p  < .05) GAG content, chondrogenic protein and gene expression level of SOX-9, COL-II, ACAN, and HIF pathway related gene (HIF-1α) were significantly higher in IGF-1 PLGA/PDA/PCL scaffolds group compared to other groups. ( p  < .05) IGF-1 PLGA/PDA/PCL scaffolds may be a better method for sustained IGF-1 administration and a promising scaffold for cartilage tissue engineering.

BACKGROUND We synthetized a 3D printed poly-ε-caprolactone (PCL) scaffold with polydopamine (PDA) coating and lithium chloride (LiCl) deposition for cartilage tissue engineering and analyzed its effect on promoting rabbit bone marrow mesenchymal stem cells (rBMSC) chondrogenesis in vitro. MATERIAL AND METHODS PCL scaffolds were prepared by 3D printing with a well-designed CAD digital model, then modified by PDA coating to produce PCL-PDA scaffolds. Finally, LiCl was deposited on the PDA coating to produce PCL-PDA-Li scaffolds. The physicochemical properties, bioactivity, and biocompatibility of PCL-PDA-Li scaffolds were accessed by comparing them with PCL scaffolds and PCL-PDA scaffolds. RESULTS 3D PCL scaffolds exhibited excellent mechanical integrity as designed. PDA coating and LiCl deposition improved surface hydrophilicity without sacrificing mechanical strength. Li⁺ release was durable and ion concentration did not reach the cytotoxicity level. This in vitro study showed that, compared to PCL scaffolds, PCL-PDA and PCL-PDA-Li scaffolds significantly increased glycosaminoglycan (GAG) formation and chondrogenic marker gene expression, while PCL-PDA-Li scaffolds showed far higher rBMSC viability and chondrogenesis. CONCLUSIONS 3D printed PCL-PDA-Li scaffolds promoted chondrogenesis in vitro and may provide a good method for lithium administration and be a potential candidate for cartilage tissue engineering.

It is difficult to achieve self-healing outcoming for the osteochondral defects caused by degenerative diseases. The simultaneous regeneration of both cartilage and subchondral bone tissues is an effective therapeutic strategy for osteochondral defects. However, it is challenging to design a single type of bioscaffold with suitable ionic components and beneficial osteo/chondral-stimulation ability for regeneration of osteochondral defects. In this study, we successfully synthesized a pure-phase lithium calcium silicate (Li 2 Ca 4 Si 4 O 13 , L 2 C 4 S 4 ) bioceramic by a sol-gel method, and further prepared L 2 C 4 S 4 scaffolds by using a 3D-printing method. The compressive strength of L 2 C 4 S 4 scaffolds could be well controlled in the range of 15-40 MPa when pore size varied from 170 to 400 μm. L 2 C 4 S 4 scaffolds have been demonstrated to possess controlled biodegradability and good apatite-mineralization ability. At a certain concentration range, the ionic products from L 2 C 4 S 4 significantly stimulated the proliferation and maturation of chondrocytes, as well as promoted the osteogenic differentiation of rBMSCs. L 2 C 4 S 4 scaffolds simultaneously promoted the regeneration of both cartilage and subchondral bone as compared to pure β-TCP scaffolds in rabbit osteochondral defects. These findings suggest that 3D-printed L 2 C 4 S 4 scaffolds with such specific ionic combination, high mechanical strength and good degradability as well as dual bioactivities, represent a promising biomaterial for osteochondral interface reconstruction., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

When osteochondral tissues suffer from focal or degenerative lesions caused by trauma or disorders, it is a tough challenge to regenerate them because of the limited self-healing capacity of articular cartilage. In this study, a series of Mo-doped bioactive glass ceramic (Mo-BGC) scaffolds were prepared and then systematically characterized. The released MoO 4 2- ions from 7.5Mo-BGC scaffolds played a vital role in regenerating articular cartilage and subchondral bone synchronously. Methods: The Mo-BGC scaffolds were fabricated through employing both a sol-gel method and 3D printing technology. SEM, EDS, HRTEM, XRD, ICPAES and mechanical strength tests were respectively applied to analyze the physicochemical properties of Mo-BGC scaffolds. The proliferation and differentiation of rabbit chondrocytes (RCs) and human bone mesenchymal stem cells (HBMSCs) cultured with dilute solutions of 7.5Mo-BGC powder extract were investigated in vitro . The co-culture model was established to explore the possible mechanism of stimulatory effects of MoO 4 2- ions on the RCs and HBMSCs . The efficacy of regenerating articular cartilage and subchondral bone using 7.5Mo-BGC scaffolds was evaluated in vivo . Results: The incorporation of Mo into BGC scaffolds effectively enhanced the compressive strength of scaffolds owing to the improved surface densification. The MoO 4 2- ions released from the 7.5Mo-BGC powders remarkably promoted the proliferation and differentiation of both RCs and HBMSCs. The MoO 4 2- ions in the co-culture system significantly stimulated the chondrogenic differentiation of RCs and meanwhile induced the chondrogenesis of HBMSCs. The chondrogenesis stimulated by MoO 4 2- ions happened through two pathways: 1) MoO 4 2- ions elicited anabolic responses through activating the HIF-1α signaling pathway; 2) MoO 4 2- ions inhibited catabolic responses and protected cartilage matrix from degradation. The in vivo study showed that 7.5Mo-BGC scaffolds were able to significantly promote cartilage/bone regeneration when implanted into rabbit osteochondral defects for 8 and 12 weeks, displaying bi-lineage bioactivities. Conclusion: The 3D-printed Mo-BGC scaffolds with bi-lineage bioactivities and activated anabolic responses could offer an effective strategy for cartilage/bone interface regeneration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To prepare dopamine modified and cartilage derived morphogenetic protein 1 (CDMP1) laden polycaprolactone-hydroxyapatite (PCL-HA) composite scaffolds by three-dimensional (3D) printing and evaluate the effect of 3D scaffolds on in vitro chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs)., Methods: A dimensional porous PCL-HA scaffold was fabricated by 3D printing. Dopamine was used to modify the surface of PCL-HA and then CDMP-1 was loaded into scaffolds. The surface microstructure was observed by scanning electron microscope (SEM) and porosity and water static contact angle were also detected. The cytological experiment in vitro were randomly divided into 3 groups: group A (PCL-HA scaffolds), group B (dopamine modified PCL-HA scaffolds), and group C (dopamine modified and CDMP-1 laden PCL-HA scaffolds). The hBMSCs were seeded into three scaffolds, in chondrogenic culture conditions, the cell adhesive rate, the cell proliferation (MTT assay), and cell activity (Live-Dead staining) were analyzed; and the gene expressions of collagen type Ⅱ and Aggrecan were detected by real-time fluorescent quantitative PCR., Results: The scaffolds in 3 groups were all showed a cross-linked and pore interconnected with pore size of 400-500 μm, porosity of 56%, and fiber orientation of 0°/90°. For dopamine modification, the scaffolds in groups B and C were dark brown while in group A was white. Similarly, water static contact angle was from 76° of group A to 0° of groups B and C. After cultured for 24 hours, the cell adhesion rate of groups A, B, and C was 34.3%±3.5%, 48.3%±1.5%, and 57.4%±2.5% respectively, showing significant differences between groups ( P <0.05). Live/Dead staining showed good cell activity of cells in 3 groups. MTT test showed that hBMSCs proliferated well in 3 groups and the absorbance ( A ) value was increased with time. The A value in group C was significantly higher than that in groups B and A, and in group B than in group A after cultured for 4, 7, 14, and 21 days, all showing significant differences ( P <0.05). The mRNA relative expression of collagen type Ⅱ and Aggrecan increased gradually with time in 3 groups. The mRNA relative expression of collagen type Ⅱafter cultured for 7, 14, and 21 days, and the mRNA relative expression of Aggrecan after cultured for 14 and 21 days in group C were significantly higher than those in groups A and B, and in group B than in group A, all showing significant differences ( P <0.05)., Conclusion: Co-culture of dopamine modified and CDMP1 laden PCL-HA scaffolds and hBMSCs in vitro can promote hBMSCs' adhesion, proliferation, and chondrogenic differentiation.

The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr 5 (PO 4 ) 2 SiO 4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro . The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo . Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Mesenchymal stem cells (MSCs), a stem cell population capable of multi‑lineage differentiation, bound to porous biomaterial scaffolds, are widely used for bone tissue regeneration. However, there is evidence to suggest that MSC collection from bone marrow and expansion in vitro may result in phenotypic changes including a loss of differentiation potential and cell senescence. The aim of the present study was to find a facile and efficient approach to enable MSC adhesion and proliferation to scaffolds with osteogenic differentiation. Unprocessed bone marrow blood from the condyle of the distal femur in the rabbits were added to three‑dimensional (3D) printed porous poly-ε-caprolactone/hydroxyapatite (PCL/HA) scaffolds with bone marrow clots (MC) formed, using two different methods for Group A (MC enriched scaffolds) and Group B (MC combined scaffolds), and then were cultured in osteogenic medium for 4 weeks. The scaffolds were assessed macroscopically and microscopically. Scaffold bioactivity and the proliferation and osteogenic differentiation of seeded MSCs were measured. Higher cellular viability and greater cell numbers in the scaffolds at later phases of culture were observed in Group B compared with Group A. In addition, Group B was associated with greater osteoinductivity, alkaline phosphatase activity and bony nodule formation, as assessed using scanning electron microscopy. Furthermore, reverse transcription‑quantitative polymerase chain reaction analysis revealed that more osteogenic differentiation was present in Group B, compared with Group A. MC combined scaffolds proved to be a highly efficient, reliable and simple novel method for MSC adhesion, proliferation and differentiation. The MC combined PCL‑HA multi‑scale porosity scaffold may represent a candidate for future bone regeneration studies.

Bacterial infection poses a significant risk with the wide application of bone graft materials. Designing bone grafts with good antibacterial performance and excellent bone-forming activity is of particular significance for bone tissue engineering. In our study, a 3D printing method was used to prepare β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Silver (Ag) nanoparticles were uniformly dispersed on graphene oxide (GO) to form a homogeneous nanocomposite (named Ag@GO) with different Ag-to-graphene oxide mass ratios, with this being synthesized via the liquid chemical reduction approach. Ag@GO nanocomposites were successfully modified on the β-TCP scaffolds by a simple soaking method to achieve bifunctional biomaterials with antibacterial and osteogenic activity. The prepared scaffolds possessed a connected network with triangle pore morphology and the surfaces of the β-TCP scaffolds were uniformly modified by the Ag@GO nanocomposite layers. The Ag content in the scaffolds was controlled by changing the coating times and concentration of the Ag@GO nanocomposites. The antibacterial activity of the scaffolds was assessed with Gram-negative bacteria (Escherichia coli, E. coli). The results demonstrated that the scaffolds with Ag@GO nanocomposites presented excellent antibacterial activity. In addition, the scaffolds coated with Ag@GO nanocomposites conspicuously accelerated the osteogenic differentiation of rabbit bone marrow stromal cells by improving their alkaline phosphatase activity and bone-related gene expression (osteopontin, runt-related transcription factor 2, osteocalcin and bone sialoprotein). This study demonstrates that bifunctional scaffolds with a combination of antibacterial and osteogenic activity can be achieved for the reconstruction of large-bone defects while preventing or treating infections.

The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation., (© The Author(s) 2015.)

Various biomaterials have been investigated in attempts to improve the mechanical stability of marrow clots derived from microfracture to obtain repaired tissue closely resembling hyaline cartilage. The goal of this study was to investigate the retention, adhesion, proliferation, and cartilage extracellular matrix (ECM) production of marrow clot-derived cells within a bone marrow mesenchymal stem cell-derived (BMSC-d) ECM/marrow clot composite scaffold. We fabricated BMSC-dECM/marrow clot composite scaffolds and kept them in chondrogenic medium in vitro for 1, 3, or 6 weeks. Unmodified marrow clots were used as a control. The BMSC-dECM/marrow clot composite scaffold exhibited a porous structure suitable for cell attachment and growth and further maintained cell viability. The DNA content measurements revealed that more cells proliferated in the BMSC-dECM/marrow clot composite scaffolds over time than in the marrow clots. Furthermore, the histologic, immunohistochemical, and western blot results demonstrated that the BMSC-dECM/marrow clot composite scaffold produced more hyaline-like cartilage and less fibrocartilage than the marrow clot in culture. Taken together, these findings indicate that the porous BMSC-dECM/marrow clot composite scaffold promotes the retention, attachment, and proliferation of cells from the marrow clot, and thus can stabilize the marrow clot to support chondrogenesis., (© 2014 Wiley Periodicals, Inc.)

Scaffolds play an important role in directing three-dimensional (3D) cartilage regeneration. Our recent study reported the potential advantages of bone marrow clots (MC) in promoting extracellular matrix (ECM) scaffold chondrogenic regeneration. The aim of this study is to build a new scaffold for MC, with improved characteristics in mechanics, shaping, and biodegradability, compared to our previous study. To address this issue, this study prepared a 3D porous polycaprolactone (PCL)-hydroxyapatite (HA) scaffold combined with MC (Group A), while the control group (Group B) utilized a bone marrow stem cell seeded PCL-HA scaffold. The results of in vitro cultures and in vivo implantation demonstrated that although an initial obstruction of nutrient exchange caused by large amounts of fibrin and erythrocytes led to a decrease in the ratio of live cells in Group A, these scaffolds also showed significant improvements in cell adhesion, proliferation, and chondrogenic differentiation with porous recanalization in the later culture, compared to Group B. After 4 weeks of in vivo implantation, Group A scaffolds have a superior performance in DNA content, Sox9 and RunX2 expression, cartilage lacuna-like cell and ECM accumulation, when compared to Group B. Furthermore, Group A scaffold size and mechanics were stable during in vitro and in vivo experiments, unlike the scaffolds in our previous study. Our results suggest that the combination with MC proved to be a highly efficient, reliable, and simple new method that improves the biological performance of 3D PCL-HA scaffold. The MC-PCL-HA scaffold is a candidate for future cartilage regeneration studies.

The study aims to investigate the techniques of design and construction of CT 3D reconstructional data-based polycaprolactone (PCL)-hydroxyapatite (HA) scaffold. Femoral and lumbar spinal specimens of eight male New Zealand white rabbits were performed CT and laser scanning data-based 3D printing scaffold processing using PCL-HA powder. Each group was performed eight scaffolds. The CAD-based 3D printed porous cylindrical stents were 16 piece × 3 groups, including the orthogonal scaffold, the Pozi-hole scaffold and the triangular hole scaffold. The gross forms, fiber scaffold diameters and porosities of the scaffolds were measured, and the mechanical testing was performed towards eight pieces of the three kinds of cylindrical scaffolds, respectively. The loading force, deformation, maximum-affordable pressure and deformation value were recorded. The pore-connection rate of each scaffold was 100 % within each group, there was no significant difference in the gross parameters and micro-structural parameters of each scaffold when compared with the design values (P > 0.05). There was no significant difference in the loading force, deformation and deformation value under the maximum-affordable pressure of the three different cylinder scaffolds when the load was above 320 N. The combination of CT and CAD reverse technology could accomplish the design and manufacturing of complex bone tissue engineering scaffolds, with no significant difference in the impacts of the microstructures towards the physical properties of different porous scaffolds under large load.

Owing to the different biological properties of articular cartilage and subchondral bone, it remains significant challenge to construct a bi-lineage constructive scaffold. In this study, manganese (Mn)-doped β-TCP (Mn-TCP) scaffolds with varied Mn contents are prepared by a 3D-printing technology. The effects of Mn on the physicochemical properties, bioactivity, and corresponding mechanism for stimulating osteochondral regeneration are systematically investigated. The incorporation of Mn into β-TCP lowers the lattices parameters and crystallization temperatures, but improves the scaffold density and compressive strength. The ionic products from Mn-TCP significantly improve the proliferation of both rabbit chondrocytes and mesenchymal stem cells (rBMSCs), as well as promote the differentiation of chondrocytes and rBMSCs. The in vivo study shows that Mn-TCP scaffolds distinctly improve the regeneration of subchondral bone and cartilage tissues as compared to TCP scaffolds, upon transplantation in rabbit osteochondral defects for 8 and 12 weeks. The mechanism is closely related to the Mn2+ ions significantly stimulated the proliferation and differentiation of chondrocytes through activating HIF pathway and protected chondrocytes from the inflammatory osteoarthritis environment by activating autophagy. These findings suggest that 3D-printing of Mn-containing scaffolds with improved physicochemical properties and bilineage bioactivities represents an intelligent strategy for regenerating osteochondral defects. [ABSTRACT FROM AUTHOR]

In article number 1807356, Yishen Zhu, Qingqiang Yao, and co‐workers develop a strategy to molecularly functionalize the self‐assembling peptide hydrogel (SAPH) FEFEFKFK onto 3D‐printed polycaprolactone (PCL) scaffolds, forming a reliable and stable coating layer. The prepared SAPH‐coated PCL scaffolds provide a superior performance for the regeneration of cartilage and subchondral bone simultaneously, offering a flexible strategy for osteochondral defects caused by osteoarthritis or acute trauma. [ABSTRACT FROM AUTHOR]

Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair. The molecularly functionalized self‐assembling peptide hydrogel‐coated polycaprolactone scaffolds provide superior performance for the regeneration of cartilage and subchondral bone simultaneously, offering a reliable and flexible strategy for osteochondral defects caused by osteoarthritis or acute trauma. [ABSTRACT FROM AUTHOR]

Treatment of osteochondral defects remains a great challenge in clinical practice because cartilage and subchondral bone possess significantly different physiological properties. In this study, the controlled surface micro/nanometer structure of bioactive scaffolds in a combination of biomaterial chemistry is harnessed to address this issue. Model bioactive biomaterials, bredigite (BRT) scaffolds, with controlled surface micro/nanostructure are successfully fabricated by combining 3D printing with a hydrothermal process. It is found that the growth of micro/nano–calcium phosphate crystals on the surface of BRT scaffolds notably enhances their compressive strength by healing the microcracks on the strut surface. The micro/nanostructured surface distinctly facilitates the spread and differentiation of chondrocytes by activating integrin αvb1 and α5b1 heterodimers, regulates cell morphology, and promotes osteogenic differentiation of rabbit bone marrow stromal cells (rBMSCs) through the synergetic effect of integrin α5b1 and RhoA, in which the microrod surface demonstrates the highest stimulatory effect on the differentiation of chondrocytes and rBMSCs. The in vivo study shows that the micro/nanostructured surface of the 3D printed scaffolds obviously promotes the regeneration of both cartilage and subchondral bone tissues. This study suggests that the construction of controlled micro/nanostructured surface in porous 3D scaffolds offers a smart strategy to induce bilineage bioactivities for osteochondral regeneration. Micro/nanostructured surfaces in bredigite scaffolds are successfully prepared via a hydrothermal process. In vitro, the micro/nanostructured surface significantly promotes differentiation of chondrocytes by activating integrins α5β1 and αvβ1, and stimulates osteogenic differentiation of rabbit bone marrow stromal cells through the synergetic effects of integrin α5β1 and RhoA. Furthermore, the micro/nanostructured surface possesses dual physiological functions for the regeneration of both cartilage and subchondral bone. [ABSTRACT FROM AUTHOR]

The lack of traditional bioactivity in zirconia (ZrO 2) and limitations in the personalization capabilities of conventional manufacturing processes pose significant challenges for alveolar bone defect repair. This study aims to investigate whether ZrO 2 /CSi-Mgx scaffolds, produced by combining magnesium-doped calcium silicate (CSi–Mg) as a doping phase with ZrO 2 as the matrix, using projection-based 3D printing (3DPP) technology, exhibit favorable biocompatibility and mechanical properties at low sintering temperatures. The effect of CSi–Mg content (x%), pore structure and heating temperature on the strength of scaffolds were investigated systematically. Incorporation of CSi–Mg could readily adjust the sintering properties of the ZrO 2 scaffolds and the scaffolds with low (10–20 %) CSi–Mg possess much higher strength (74–92 MPa) after 1150 °C. Meanwhile, the ZrO 2 /CSi–Mg10 scaffolds with Triply periodic minimum surfaces (TPMS) pore structure had a compression strength of over 92 MPa and maintained a respectable strength (63 MPa) even after immersion in Tris buffer for 6 weeks. Concurrently, cellular experiments showed that incorporation of CSi–Mg could enhance cellular adhesion, proliferation, and migration of the ZrO 2 scaffolds and also promote the osteogenic property of the scaffolds. In conclusion, the ZrO 2 /CSi–Mg10 scaffold with TPMS pore structure showcases remarkable mechanical performance and bioactivity, holding the potential to facilitate in-situ bone regeneration within the alveolar bone. [ABSTRACT FROM AUTHOR]