Polycaprolactone Scaffolds Research Articles

Evaluation of the physico‐mechanical properties, mineralization capability, degradability and biological behavior of PCL/SBG composite scaffolds fabricated by three‐dimensional fiber deposition

AbstractIn bone tissue engineering, polycaprolactone (PCL) has been extensively employed as a bone substitute due to its good biocompatibility, outstanding mechanical properties, controllable degradation rate, and excellent processability. However, PCL is a bioinert polymer with poor hydrophilicity, and it fails to actively induce new bone formation after implantation into the lesion. Therefore, it is generally necessary to find a bioactive material to improve these deficiencies of PCL. In this study, we first prepared a silicate‐based bioactive glass (SBG, 48SiO2‐24Na2O‐24CaO‐4P2O5, in mol%) using the melt‐quenching method, and then fabricated a series of PCL/SBG composite scaffolds with varying SBG powder contents (0, 10, 20, 30, and 40 wt.%) by 3D fiber deposition. The physico‐mechanical properties, mineralization capability, degradability and biological behavior of PCL/SBG scaffolds were systematically characterized. The results showed that the contact angle of the scaffolds decreased from 121.90 ± 3.74° to 86.29 ± 3.46° with the increase of SBG content, implying that the hydrophilicity was improved, and meanwhile the porosity and mechanical strength of PCL/SBG scaffolds first increased and then decreased, but they were within the range of human cancellous bone. Additionally, the degradation rate of PCL/SBG groups can be regulated by adjusting the SBG content. Finally, compared to the pure PCL group, the cell viability and alkaline phosphatase activity of MC3T3‐E1 on PCL/SBG groups were significantly enhanced. In the present work, the PCL/30SBG group exhibited great potential as a viable alternative to autografts and offers promising clinical applications for bone defect repair in the future.Highlights The addition of SBG powders accelerates the degradation of PCL. The addition of SBG powders enhances the hydrophilicity of PCL scaffolds. The degradation rate and bioactivity of PCL/SBG scaffolds can be regulated. The mechanical strength is within the range of human cancellous bone. PCL/30SBG shows improved cell viability and ALP activity.

Incorporating a poly-ε-caprolactone scaffold in a stapled small intestinal anastomosis with induced ischemia significantly increased anastomotic tensile strength. An experimental study in pigs

Objective Anastomotic leakage is a severe complication with multifactorial aetiology, including impaired tissue oxygenation, infection, inflammation, and anastomotic tension. Reinforcement with poly-ε-caprolactone (PCL) scaffold incorporated in a stapled intestinal anastomosis has demonstrated a significant increase in the anastomotic tensile strength. This study aimed to investigate whether incorporation of the scaffold would influence tensile strength with induced ischemia compared to normal blood perfusion. Methods Eighteen pigs were randomly allocated into an intervention group with a induced relative reduction in blood perfusion to 30% at the anastomotic area and a control group with normal perfusion controlled by quantitative fluorescence angiography. Each pig recieved two stapled small intestinal anastomoses, one with a PCL scaffold incorporated and one without. On postoperative day five, the anastomoses were subjected to a maximal tensile strength test (MATS) and a histopathological analysis. Tensile strength was measured at three events: when a serosal tear became visible (MATS-1), at transmural rupture (MATS-2), and at maximum load before the load-strain curve dropped (MATS-3). Results In the intervention group, MATS-1 was significantly higher in scaffold-reinforced anastomoses compared to controls (7.9 ± 4.2N and 4.4 ± 2.5N, p < 0.02). The same tendency was found for MATS-2 and MATS-3, with statistically significant differences after adjusting for adhesion grade (p < 0.05). Histological analysis revealed no significant differences in wound healing between groups. Conclusion Incorporating a PCL scaffold in a stapled small intestinal anastomosis with induced ischemia improved anastomotic tensile strength.

Electrospun Polycaprolactone-Curcumin Scaffolds: Optimization of fiber production for enhanced Nanotopography and improved biological cell adhesion

Curcumin, a natural polyphenolic compound with well-documented anti-inflammatory, antioxidant, and anticancer properties, has gained attention for its potential in tissue regeneration and other biomedical applications. Despite this, the integration of curcumin into polymeric scaffolds remains challenging due to its hydrophobic nature and stability concerns. This study aims to overcome these limitations by developing and characterizing curcumin-loaded polycaprolactone (PCL) scaffolds through electrospinning, a technique selected based on a comprehensive review of recent advances in the field. In this work, PCL scaffolds were fabricated with curcumin concentrations of 5, 10, and 15 mg and analyzed using advanced microscopy, spectroscopy, thermogravimetry, mechanical testing, and biological assays. Microscopy revealed that increasing curcumin concentrations improved fiber diameter uniformity and distribution. Raman spectroscopy confirmed the homogeneous incorporation of curcumin within the scaffolds, showing that up to 10 mg, the electrospinning process induces a transition of curcumin from its di-keto to its more reactive keto-enol form. This transformation facilitates hydrogen bonding with the PCL matrix, enhancing the scaffolds’ mechanical properties.In vitro cytotoxicity assays demonstrated high cell viability across all scaffolds after 24 and 72 h. Furthermore, adhesion studies with fibroblast BJ-1 cells indicated significantly improved cell adhesion on curcumin-loaded scaffolds compared to pure PCL. These findings highlight the biocompatibility and bioactivity of curcumin-loaded PCL scaffolds.This study examines the possible use of curcumin’s controlled integration into PCL scaffolds for tissue regeneration applications. The innovative approach detailed here offers a scalable and effective pathway for the development of biomaterials that combine mechanical strength, bioactivity, and biocompatibility, addressing a critical need in tissue engineering.

Bone replacement material with optimized structure, manufactured using additive printing technology

Abstract Additive manufacturing with Arburg Plastic Freeforming (APF), an extrusion-based additive manufacturing process, was used to produce biomimetic bone scaffolds for assistance of osteosynthesis made of poly-caprolactone (PCL) with channel structures for the ingrowth of blood vessels. The specific creation of defined channel structures is very important to support the ingrowth of blood vessels, which significantly supports the regeneration of natural tissue. The tibia model used was divided into the corticalis and the spongiosa to be able to compare the realization of the different requirements of the two natural structures with the printed structures separately. Microtome cuts of the manufactured bone scaffolds with channels were prepared for characterization with light microscopy. Compression tests were carried out on a tensile testing machine. It was found that the channels in the tibial cortex led to a slightly higher stiffness compared to those without channels due to the frame outlines. Overall, however, the stiffness of the Polycaprolactone (PCL) scaffolds was significantly lower than that of natural bone. In the spongiosa scaffolds, the stiffness with channels was lower than that without channels, but still within the physiological range, as was the model without channels. The porosity was within the required range for both scaffold types.

Hybrid 3D bioprinting for advanced tissue-engineered trachea: merging fused deposition modeling (FDM) and top–down digital light processing (DLP)

In this present study, we introduce an innovative hybrid 3D bioprinting methodology that integrates fused deposition modeling (FDM) with top-down digital light processing (DLP) for the fabrication of an artificial trachea. Initially, polycaprolactone (PCL) was incorporated using an FDM 3D printer to provide essential mechanical support, replicating the structure of tracheal cartilage. Subsequently, a chondrocyte-laden glycidyl methacrylated silk fibroin hydrogel was introduced via top-down DLP into the PCL scaffold (PCL-Sil scaffold). The mechanical evaluation of PCL-Sil scaffolds showed that they have greater flexibility than PCL scaffolds, with a higher deformation rate (PCL-Sil scaffolds: 140.9% ± 5.37% vs. PCL scaffolds: 124.3% ± 6.25%) and ability to withstand more force before fracturing (3.860 ± 0.140 N for PCL-Sil scaffolds vs. 2.502 ± 0.126 N for PCL scaffolds, ***P< 0.001). Both types of scaffolds showed similar axial compressive strengths (PCL-Sil scaffolds: 4.276 ± 0.127 MPa vs. PCL scaffolds: 4.291 ± 0.135 MPa). Additionally, PCL-Sil scaffolds supported fibroblast proliferation, indicating good biocompatibility.In vivotesting of PCL-Sil scaffolds in a partial tracheal defect rabbit model demonstrated effective tissue regeneration. The scaffolds were pre-cultured in the omentum for two weeks to promote vascularization before transplantation. Eight weeks after transplantation into the animal, bronchoscopy and histological analysis confirmed that the omentum-cultured PCL-Sil scaffolds facilitated rapid tissue regeneration and maintained the luminal diameter at the anastomosis site without signs of stenosis or inflammation. Validation study to assess the feasibility of our hybrid 3D bioprinting technique showed that structures, not only the trachea but also the vertebral bone-disc and trachea-lung complex, were successfully printed.

Bioactive Coatings on 3D Printed Polycaprolactone Scaffolds for Bone Regeneration: A Novel Murine Femur Defect Model for Examination of the Biomaterial Capacity for Repair

AbstractBone tissue engineering seeks to develop treatment approaches for nonhealing and large bone defects. An ideal biodegradable scaffold will induce and support bone formation. The current study examines bone augmentation in critical‐sized bone defects, using functionalized scaffolds, with the hypothesized potential to induce skeletal cell differentiation. 3D printed, porous poly(caprolactone) trimethacrylate (PCL‐TMA900) scaffolds are applied within a murine femur defect, stabilized by a polyimide intramedullary (IM) pin. The PCL‐TMA900 scaffolds are coated with i) elastin‐like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA)/fibronectin (FN)/bone morphogenetic protein‐2 (PEA/FN/BMP‐2), iii) both ELP and PEA/FN/BMP‐2, or iv) Laponite nanoclay binding BMP‐2. Sequential microcomputed tomography (µCT) and histological analysis are performed. PCL‐TMA900 is robust and biocompatible and when coated with the nanoclay material Laponite and BMP‐2 induce consistent, significant bone formation compared to the uncoated PCL‐TMA900 scaffold. Critically, the BMP‐2 is retained, due to the Laponite, producing bone around the scaffold in the desired shape and volume, compared to bone formation observed with the positive control (collagen sponge/BMP‐2). The ELP and/or PEA/FN/BMP‐2 scaffolds do not demonstrate significant or consistent bone formation. In summary, Laponite/BMP‐2 coated PCL‐TMA900 scaffolds offer a biodegradable, osteogenic construct for bone augmentation with potential for development into a large scale polymer scaffold for clinical translation.

Grafting of phosphonylated polymers onto 3D printed polycaprolactone scaffolds improves osteoblasts proliferation and calcium mineralization in-vitro

Prosthesis implantation or bone grafting are currently used to treat bone defects induced by osteoporosis, bone tumors or fractures. However, these conventional surgical techniques can lead to significant complications, including infection, loosening, and rejection. Consequently, additional surgeries or even amputation of the affected limb may become necessary. In this context, advancing the strategies used for bone repair remains a critical challenge. The present preliminary study outlines a method for developing biodegradable and bioactive PCL implants with improved osteoblast biological response for bone regeneration., vinylbenzylphosphonic acid (VBP) monomer was grafted and polymerized onto the 3D printed cylindrical polycaprolactone (PCL) implants using a two-step UV irradiation process. To refine and optimize the grafting conditions, key parameters such as ozonation time, UV irradiation duration, and reaction medium were adjusted. The success of the grafting process was assessed using various characterization techniques, including colorimetry, contact angle measurements, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Attenuated Total Reflection-Fourrier Transform Infrared Spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and size-exclusion chromatography (SEC). Furthermore, a study of the cellular response focusing on viability, morphology, and mineralization was conducted using mouse preosteoblasts (MC3T3-E1 cell line). The results demonstrated the beneficial effects of grafting a bioactive polymer containing a phosphonate group onto implant surfaces.

Antibacterial bioadaptive scaffold promotes vascularized bone regeneration by synergistical action of intrinsic stimulation and immunomodulatory activity

The coupling of angiogenesis and osteogenesis is the fundamental necessity in bone fracture healing, thus simulative action of tissue-engineered bone provides powerful and beneficial effects in the treatment of bone defect. Herein, an immunoregulatory biocomposite scaffold with intrinsic activities of coupling angiogenesis and osteogenesis was constructed based on polyelectrolytes-modified 3D-printed scaffold for enhanced bone regeneration. The doping of Sr-doped hydroxyapatite (SrHA) within 3D-printed polycaprolactone (PCL) scaffold and subsequent slit guidance ligand 3 (SLIT3) protein adsorption through surface coating of carboxymethyl chitosan (CCS)/hyperbranched polylysine (HBPL) achieved on-demand delivery of SLIT3 and Sr ions. The antibacterial property of polyelectrolytes-modified scaffold was characterized and was directly proportional to the layer number of polyelectrolytes coating. The dual-factor delivery scaffold had good biocompatibility to support cell proliferation and migration, and was capable of stimulating angiogenesis and osteogenesis by intrinsic stimulation from released SLIT3 protein and Sr ions. Importantly, the multifunctional scaffold had immunomodulatory effects of promoting M2-type polarization of macrophages and thereby increasing anti-inflammatory factors level, as well as indirectly promoting angiogenesis and osteogenesis. The in vivo experiments revealed that the anti-inflammatory effect was significantly reinforced for providing a better regenerative microenvironment and bone regeneration capacity was dramatically enhanced accompanied with type H vessels formation when implanted with multifunctional scaffold. Therefore, the bioadaptive scaffold possessed amplified bone regeneration performance through intrinsic stimulation and immunomodulatory effects, suggesting a promising therapeutic candidate for bone defect repair.

3D-Printed Bifunctional Scaffold for Treatment of Critical Bone Defects Based on Osteoimmune Microenvironment Regulation and Osteogenetic Effects.

The critical-sized bone defect resulting from trauma, tumor resection, and congenital deformity fails to undergo spontaneous healing due to its substantial size, while the ensuing inflammatory process and hypoxic environment further impede the regenerative process. Therefore, it has consistently presented a significant clinical challenge. In the present study, we incorporate a glycyrrhizic acid (GA)-functionalized hydrogel onto the surface of a Hydroxyapatite (Hap)-modified Polycaprolactone (PCL) scaffold to fabricate a composite scaffold. The composed scaffold showed favorable anti-inflammatory and antioxidative capabilities by modulating macrophage polarization and scavenging reactive oxygen species (ROS); the modification of Hap enhanced its osteogenic ability. An in vivo rat skull defect model confirmed that the composed scaffold efficiently promotes bone regeneration. In general, the composed scaffold with the ability of osteoimmune microenvironment regulation can effectively repair critical-sized bone defects. This strategy provides a promising method for the reconstruction of large segmental bone defects.

Polydopamine-Modified Polycaprolactone Scaffolds Loading Metal Nanoparticles for Bone Tissue Engineering.

Recent advancements in materials synthesis and processing technology, coupled with a deeper understanding of bone nanoscale structure and biology, have provided new avenues for designing bioactive materials in bone tissue regenerative medicine. This Review focuses on the design and application of polydopamine-modified polycaprolactone scaffolds loading metal nanoparticles for bone tissue engineering. We explore their antibacterial properties and their ability to guide cell behavior. Specifically, we discuss the synthesis techniques, protein deposition, morphology variations, and interactions with the extracellular matrix of these scaffolds and biocompatibility and efficacy in promoting bone tissue regeneration in vitro and in vivo. Challenges and unmet needs are reviewed in the development of polymer- and metal-based materials for bone tissue engineering.

Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells.

Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing at LT produced less stiff and highly flexible scaffolds (E: 53 ± 10 MPa and strain: 435 ± 105%). Moreover, the introduction of porosity by salt leaching in the printed filaments significantly changed the mechanical properties and degradation rate of the scaffolds. Furthermore, this study aimed to show how these variations influence proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC) and the maturation and activation of human monocyte-derived dendritic cells (Mo-DC). The cytocompatibility of the printed scaffolds was confirmed by live-dead imaging, metabolic activity measurement, and the continuous proliferation of hBMSC over 14 days. While all scaffolds facilitated the expression of osteogenic markers (RUNX2 and Collagen I) from hBMSC as detected through immunofluorescence staining, the variation in porosity and stiffness notably influenced the early and late mineralization. Furthermore, the flexible LT scaffolds, with porosity induced by NIPS and salt leaching, stimulated Mo-DC to adopt a pro-inflammatory phenotype marked by a significant increase in the expression of IL1B and TNF genes, alongside decreased expression of anti-inflammatory markers, IL10 and TGF1B. Altogether, the results of the current study demonstrate the importance of tailoring porosity and stiffness of PCL scaffolds to direct their biological performance toward a more immune-mediated bone healing process.

Synchronized long-term delivery of growth hormone and insulin-like growth factor 1 through poly (lactic-co-glycolic acid) nanoparticles on polycaprolactone scaffolds for enhanced osteochondral regeneration

The regeneration of osteochondral defects is challenging due to the complex structure of the osteochondral unit. This study aimed to develop a biomimetic scaffold by loading growth hormone (GH) and insulin-like growth factor-1 (IGF-1) into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and incorporating them into polycaprolactone (PCL) scaffolds to promote synchronized osteochondral regeneration. The nanoparticles were successfully immobilized onto PCL scaffolds pre-modified with polydopamine (PDA) to enhance cell adhesion and proliferation. The scaffolds exhibited a sustained release of GH and IGF-1 over 30 days. In vitro studies using rabbit adipose-derived stem cells (ADSCs) showed that the GH/IGF-1 nanoparticle-loaded scaffolds (PCL/PDA/M-PLGA) significantly promoted cell proliferation, chondrogenic differentiation, and osteogenic differentiation compared to control PCL/PDA scaffolds. In vivo experiments using a rabbit osteochondral defect model revealed that the PCL/PDA/M-PLGA scaffolds facilitated superior osteochondral regeneration, evidenced by increased subchondral bone formation and cartilage matrix deposition. Overall, this study demonstrates the potential of GH/IGF-1 nanoparticle-loaded PCL scaffolds for synchronized osteochondral regeneration and provides a promising strategy for treating osteochondral defects.

P-50952666-1402 - Customized Polycaprolactone Scaffold Versus Ready-Made Polycaprolactone Plug for Bone Regeneration in Intraoral Defects: A Preliminary Prospective Study

P-50952666-1402 - Customized Polycaprolactone Scaffold Versus Ready-Made Polycaprolactone Plug for Bone Regeneration in Intraoral Defects: A Preliminary Prospective Study

Biomimetic Mineralized Organic–Inorganic Hybrid Scaffolds From Microfluidic 3D Printing for Bone Repair

AbstractBone defect is a common clinical orthopedic disease. The trend in this field is to develop tissue engineering scaffolds with appropriately designed components and structures for bone repair. Herein, inspired by the organic and inorganic components of bone matrix and the natural biomineralization mechanism, a MgSiO3@Fe3O4 nanoparticle composite polycaprolactone (PCL) hybrid mineralized scaffold for bone repair is developed by microfluidic 3D printing. The incorporation of MgSiO3@Fe3O4 within the PCL scaffold can effectively improve the bioactivity. In addition, a biomimetic mineralized layer is prepared on the surface of the scaffold, which endowed it with unique microstructural characteristics, enhanced cell adhesion and osteogenic activity, and thus improved the bone repair performance. Owing to these advantages, both in vivo and in vitro experiments have demonstrated that the designed scaffold has outstanding biocompatibility and bone repair performance. These features indicate that the organic–inorganic biomineralized hybrid scaffold can be a potential bone graft substitute for clinical bone repair.

Electrohydrodynamic Printing of Microscale Fibrous Scaffolds with a Sinusoidal Structure for Enhancing the Contractility of Cardiomyocytes.

Mimicking the curved collagenous fibers in the cardiac extracellular matrix to fabricate elastic scaffolds in vitro is important for cardiac tissue engineering. Here, we developed sinusoidal polycaprolactone (PCL) fibrous scaffolds with commendable flexibility and elasticity to enhance the contractility of primary cardiomyocytes by employing melt-based electrohydrodynamic (EHD) printing. Microscale sinusoidal PCL fibers with an average diameter of ∼10 μm were printed to mimic the collagenous fibers in the cardiac ECM. The sinusoidal PCL fibrous scaffolds were EHD-printed in a layer-by-layer manner and exhibited outstanding flexibility and elasticity compared with the straight ones. The sinusoidal PCL scaffolds provided an elastic microenvironment for the attaching and spreading of primary cardiomyocytes, which facilitated their synchronous contractive activities. Primary cardiomyocytes also showed improved gene expression and maturation on the sinusoidal PCL scaffolds under electrical stimulation for 5 days. It is envisioned that the proposed flexible fibrous scaffold with biomimetic architecture may serve as a suitable patch for tissue regeneration and repair of damaged hearts after myocardial infarction.

Biodegradable Polycaprolactone Bone Scaffold for Rhinoplasty in Bilateral Cleft Repair: A Case Report

Cleft nasal deformities are commonly observed in patients with unilateral or bilateral cleft lip, presenting various degrees of severity. Correcting nasal deformities, particularly in bilateral cleft lip patients, remains a complex challenge due to underlying anatomical abnormalities and the scarring from previous surgeries. This research aims to evaluate the effectiveness of secondary cleft rhinoplasty, focusing on addressing the hypoplastic and depressed bony structures critical to nasal projection. In many cases, autologous grafts, such as cartilage from the septum, ear, or rib, are traditionally used for nasal reconstruction. However, these materials present challenges, including donor site morbidity and tissue resorption. In this study, we explore the use of Osteopore™, a biodegradable polycaprolactone scaffold, as a bone substitute for nasal reconstruction. The results indicate that Osteopore™ offers a promising alternative with reduced morbidity and stable long-term outcomes. This method provides new insights into the materials and techniques for addressing cleft nasal deformities in bilateral cleft lip patients, potentially improving both aesthetic and functional outcomes.

Bioengineering strategy to promote CNS nerve growth and regeneration via chronic glutamate signaling

Being part of the mature mammalian central nervous system, impairments of the retina and optic nerves caused by trauma or diseases often cannot be restored. Progressive degeneration of retinal ganglion cells (RGCs) in glaucoma and other optic neuropathies gradually leads to permanent vision loss, which currently has no cure. The purpose of this study is to develop a biocompatible scaffold to support RGC survival and guide axon growth, facilitating optic nerve repair and regeneration. We here report that electrical stimulation (ES) significantly promoted neurite outgrowth and elongation from primary RGCs, mediated through glutamate receptor signaling. To mimic prolonged glutamate stimulation and facilitate sustained nerve growth, we fabricated biocompatible poly-γ-benzyl-L-glutamate (PBG) scaffolds for controlled glutamate release. These PBG scaffolds supported RGC survival and robust long-distance nerve growth in both retinal explants and isolated RGC cultures. In contrast, control polycaprolactone (PCL) scaffolds with similar physical structures showed little benefits on RGC survival or nerve growth. Moreover, PBG scaffolds promoted the differentiation and neurite outgrowth from embryonic stem cell-derived RGC progenitors. The aligned PBG scaffold drove directed nerve elongation along the fiber alignment. Transplantation of PBG-coated biocompatible conduits induced robust optic nerve regeneration in adult mice following nerve transection. Together, the findings present the exciting possibility of driving optic nerve regeneration and RGC progenitor cell differentiation by imitating ES or glutamate signaling. PBG presents a permissive biomaterial in supporting robust and directed axon growth with promising clinical applications in the future. Statement of SignificanceWe here reported compelling findings that demonstrate the potent regenerative effects of a bioengineered scaffold incorporating poly-γ-benzyl-L-glutamate (PBG) on the optic nerve. Retinal ganglion cell (RGC) axons, which form the optic nerve, are incapable of regenerating in adulthood, posing a significant hurdle in restoring vision for patients with optic nerve diseases or injuries. Built upon the finding that electrical stimulation promotes RGC axonal growth through glutamate signaling, we developed PBG scaffolds to provide sustained glutamate stimulation and showed their exceptional effects on driving directed axonal elongation in cultured RGCs and neural progenitors, as well as supporting robust optic nerve regeneration after transection in vivo. The findings hold great promise for reversing vision loss in patients with optic nerve conditions.

A framework for digital twin integration in biofabrication and a scaffold 3D bioplotting case study

Biofabrication, which integrates biological sciences with advanced manufacturing, is vital for innovations in tissue engineering and regenerative medicine. One primary consideration in this domain is ensuring consistent, scalable, and adaptable processes that are amenable to clinical translation. Toward this, this paper introduces a new framework for digital twin integration in biofabrication. Digital twins, which are real-time virtual replicas of physical systems, can facilitate comprehensive monitoring, accurate prediction, and effective optimization to enable robust biofabrication processes and systems. The proposed framework incorporates major building blocks for implementing digital twins for biofabrication, including comprehensive data acquisition and analysis using sophisticated sensors to integrate biological, material, and process data; advanced modeling methods utilizing traditional and machine learning algorithms to refine process parameters; and feedback loop for real-time process adjustments. The first phase of the framework is demonstrated through a case study highlighting process optimization of 3D bioplotting of polycaprolactone (PCL) scaffolds. The digital twin’s insights streamline decisions on bioplotting parameters and post-processing, ensuring that the printed scaffold meets the desired mechanical and biological properties, thereby significantly enhancing cell proliferation and printing resolution. Key benefits of this approach include optimized biofabrication outcomes by integrating physical and biological models, promoting scalability and reproducibility with an accelerated research and development phase. This work underlines the promise of digital convergence in biofabrication, which can accelerate advancements in regenerative medicine and tissue engineering.

Assessing design-induced elasticity of 3D printed auxetic scaffolds for tissue engineering applications

Auxetic scaffolds fabricated via additive manufacturing can enable cyclic mechanical stimulation to promote the biomechanical functionalization of engineered tissues. Typical designs of additively manufactured scaffolds used in tissue engineering literature (e.g., 0/90˚ strand laydown) are not amenable to cyclic loading due to their rigidity, which is in part due to the high stiffness of biopolymers such as polycaprolactone (PCL). Auxetic scaffolds can help overcome this due to their design-induced elasticity while recapitulating negative Poisson’s ratios seen in various natural tissues. In this study, we investigated the effects of auxetic design patterns and unit cell sizes on the mechanical properties of 3D bioplotted PCL scaffolds. First, we assessed the monotonic tensile properties of two auxetic patterns – re-entrant honeycomb and missing rib (unit cell = 3 × 3 mm2 for both) – in comparison to a uniaxial control (0/0˚ strand laydown) using finite element analysis (FEA) and experimental design (n = 3/group). The results showed that the scaffold design significantly impacted scaffold elasticity (p < 0.05), with the missing rib auxetic design demonstrating significantly higher yield strain (48.2 %) compared to the re-entrant honeycomb design (11.0 %) and the control (4.8 %). The missing rib design also possessed significantly lower elastic modulus and tensile strength (11.5 MPa/g and 10 MPa/g, respectively) compared to the re-entrant honeycomb (58 MPa/g and 35.7 MPa/g, respectively) (p < 0.05). For the missing rib design, we further investigated the effect of unit cell size (2 × 2, 3 × 2, 3 × 3 mm2) on the mechanical properties. Both 3 × 2 and 3 × 3 mm2 unit cell scaffolds (n = 3/group) possessed similar mechanical properties whereas the 2 × 2 mm2 unit cell scaffolds possessed significantly lower yield strain and higher elastic modulus and tensile strength (p < 0.05). The missing rib auxetic scaffolds were also tested under tensile cyclic loading for up to 6000 cycles at 10 % of maximum strain at 0.5 Hz. The 2 × 2 mm2 unit cell scaffolds degraded significantly faster than the other two groups. Overall, the 3 × 2 mm2 unit cell scaffolds performed better under cyclic loading in terms of maintaining their tensile strength. Finally, biocompatibility testing of the missing rib 3 × 2 mm2 unit cell scaffolds demonstrated their ability to support the adhesion and viability of fibroblast cells. In future, this knowledge will be leveraged to engineer scaffolds for connective tissues such as tendons and cardiac muscle.

Conjugated electrospinning toward a polycaprolactone scaffold simultaneously containing micro-/nano- fibers for potential biomedical application

Conjugated electrospinning toward a polycaprolactone scaffold simultaneously containing micro-/nano- fibers for potential biomedical application