bims-biprem 2025-01-05 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2025–01–05
twelve papers selected by
Seerat Maqsood, University of Teramo

Skin substitutes: from conventional to 3D bioprinting.
3D Bioprinting of Graphene Oxide-Incorporated Hydrogels for Neural Tissue Regeneration.
4D bioprinting of transformable living constructs with sustained local growth factor presentation for advanced tissue engineering applications.
Enhancing bone regeneration through 3D printed biphasic calcium phosphate scaffolds featuring graded pore sizes.
Perspective of 3D culture in medicine: transforming disease research and therapeutic applications.
Template-Assisted Electrospinning and 3D Printing of Multilayered Hierarchical Vascular Grafts.
3D-printed Ti3C2/polycaprolactone composite scaffold with a DOPA-SDF1 surface modified for bone repair.
A preliminary study of cell-based bone tissue engineering into 3D-printed β-tricalcium phosphate scaffolds and polydioxanone membranes.
3D-printed cannabidiol hollow suppositories for treatment of epilepsy.
A 3D bioprinted potential colorectal tumor model based on decellularized matrix/gelatin methacryloyl/nanoclay/sodium alginate hydrogel.
Application of 3D-printed porous prosthesis for the reconstruction of infectious bone defect with concomitant severe soft tissue lesion: a case series of 13 cases.
Cutting-edge 3D printing in immunosensor design for early cancer detection.

J Artif Organs. 2024 Dec 31.

Skin substitutes: from conventional to 3D bioprinting.

C Deepa, Anugya Bhatt.

  Three-dimensional bioprinting is getting enormous attention among the scientific community for its application in complex regenerative tissue engineering applications. One of the focus areas of 3-D bioprinting is Skin tissue engineering. Skin is the largest external organ and also the outer protective layer is prone to injuries due to accidents, burns, pathologic diseases like diabetes, and immobilization of patients due to other health conditions, etc. The demand for skin tissue and the need for an off-the-shelf skin construct to treat patients is increasing on an alarming basis. Conventional approaches like skin grafting increase morbidity. Other approaches include acellular grafts, where integration with the host tissue is a major concern. The emerging technology of the future is 3D bioprinting, where different biopolymers or hybrid polymers together provide the properties of extracellular matrix (ECM) and tissue microenvironment needed for cellular growth and proliferation. This raises the hope for the possibility of a shelf skin construct, which can be used on demand or even skin can be printed directly on the wound site (in-situ printing) based on the depth and complex structure of the wound site. In the present review article, we have tried to provide an overview of Skin tissue engineering, Conventional advancement in technology, 3D bioprinting and bioprinters for skin 3D printing, different biomaterials for skin 3D bioprinting applications, desirable properties of biomaterials and future challenges.

Keywords:  Biomaterials; Bioprinters; Skin 3D bioprinting

DOI:  https://doi.org/10.1007/s10047-024-01481-9
3D Print Addit Manuf. 2024 Dec;11(6): e2022-e2032

3D Bioprinting of Graphene Oxide-Incorporated Hydrogels for Neural Tissue Regeneration.

Jiahui Lai, Xiaodie Chen, Helen H Lu, Min Wang.

  Bioprinting has emerged as a powerful manufacturing platform for tissue engineering, enabling the fabrication of 3D living structures by assembling living cells, biological molecules, and biomaterials into these structures. Among various biomaterials, hydrogels have been increasingly used in developing bioinks suitable for 3D bioprinting for diverse human body tissues and organs. In particular, hydrogel blends combining gelatin and gelatin methacryloyl (GelMA; "GG hydrogels") receive significant attention for 3D bioprinting owing to their many advantages, such as excellent biocompatibility, biodegradability, intrinsic bioactive groups, and polymer networks that combine the thermoresponsive gelation feature of gelatin and chemically crosslinkable attribute of GelMA. However, GG hydrogels have poor electroactive properties, which hinder their applications in neural tissue engineering where electrical conductivity is required. To overcome this problem, in this study, a small amount of highly electroactive graphene oxide (GO) was added in GG hydrogels to generate electroactive hydrogels for 3D bioprinting in neural tissue engineering. The incorporation of GO nanoparticles slightly improved mechanical properties and significantly increased electrical conductivity of GG hydrogels. All GO/GG composite hydrogels exhibited shear thinning behavior and sufficient viscosity and hence could be 3D printed into 3D porous scaffolds with good shape fidelity. Furthermore, bioinks combining rat bone marrow-derived mesenchymal stem cells (rBMSCs) with GO/GG composite hydrogels could be 3D bioprinted into GO/GG constructs with high cell viability. GO nanoparticles in the constructs provided ultraviolet (UV) shading effect and facilitated cell survival during UV exposure after bioprinting. The GO/GG composite hydrogels appear promising for 3D bioprinting applications in repairing damaged neural tissues.

Keywords:  3D bioprinting; graphene oxide; hydrogel scaffold; mesenchymal stem cell; neural tissue engineering

DOI:  https://doi.org/10.1089/3dp.2023.0150
Colloids Surf B Biointerfaces. 2024 Dec 27. pii: S0927-7765(24)00743-4. [Epub ahead of print]248 114484

4D bioprinting of transformable living constructs with sustained local growth factor presentation for advanced tissue engineering applications.

Guodong Wu, Lin Wang, Yuhang Cao, Manli Wang, Chun Yang, Jian Zhang.

  Traditional tissue engineering strategies focus on geometrically static tissue scaffolds, lacking the dynamic capability found in native tissues. The emerging field of 4D bioprinting offers a promising method to address this challenge. However, the requirement for consistent exogenous supplementation of growth factors (GFs) during tissue maturation poses a significant obstacle for in vivo application of 4D bioprinted constructs. We herein developed composite bioinks composed of photocrosslinkable, jammed alginate methacrylate (AlgMA) and gelatin methacrylate (GelMA), incorporating GelMA microspheres loaded with GFs to provide sustained local GF presentation over 50 days for 4D tissue bioprinting. The composite bioink exhibited excellent printability, enabling 3D printing with good accuracy (∼120 %) and fidelity (105 % - 114 %). By incorporating a photoabsorbent to enhance light attenuation, a gradient network along the light propagation pathway was generated, facilitating programmable and controllable 4D shape transformation. This process allowed the fabrication of complex living constructs with defined architectures through morphing. A proof-of-concept study on cartilage regeneration demonstrated the effectiveness of sustained GF presentation in driving tissue development, showing significant glycosaminoglycan production (GAG/DNA 10.3), and substantial upregulation of type II collagen (125.8-fold) and aggrecan (16.4-fold) mRNA expression, thereby eliminating the need for exogenous GF supplementation. This study underscores the transformative potential of integrating dynamic tissue scaffolding with sustained GF delivery, thereby addressing key limitations of traditional tissue engineering approaches and offering new avenues for tissue repair applications.

Keywords:  4D bioprinting; growth factor; local presentation; stress mismatch; tissue engineering

DOI:  https://doi.org/10.1016/j.colsurfb.2024.114484
Bioact Mater. 2025 Apr;46 21-36

Enhancing bone regeneration through 3D printed biphasic calcium phosphate scaffolds featuring graded pore sizes.

Yue Wang, Yang Liu, Shangsi Chen, Ming-Fung Francis Siu, Chao Liu, Jiaming Bai, Min Wang.

  Human long bones exhibit pore size gradients with small pores in the exterior cortical bone and large pores in the interior cancellous bone. However, most current bone tissue engineering (BTE) scaffolds only have homogeneous porous structures that do not resemble the graded architectures of natural bones. Pore-size graded (PSG) scaffolds are attractive for BTE since they can provide biomimicking porous structures that may lead to enhanced bone tissue regeneration. In this study, uniform pore size scaffolds and PSG scaffolds were designed using the gyroid unit of triply periodic minimal surface (TPMS), with small pores (400 μm) in the periphery and large pores (400, 600, 800 or 1000 μm) in the center of BTE scaffolds (designated as 400-400, 400-600, 400-800, and 400-1000 scaffold, respectively). All scaffolds maintained the same porosity of 70 vol%. BTE scaffolds were subsequently fabricated through digital light processing (DLP) 3D printing with the use of biphasic calcium phosphate (BCP). The results showed that DLP 3D printing could produce PSG BCP scaffolds with high fidelity. The PSG BCP scaffolds possessed improved biocompatibility and mass transport properties as compared to uniform pore size BCP scaffolds. In particular, the 400-800 PSG scaffolds promoted osteogenesis in vitro and enhanced new bone formation and vascularization in vivo while they displayed favorable compressive properties and permeability. This study has revealed the importance of structural design and optimization of BTE scaffolds for achieving balanced mechanical, mass transport and biological performance for bone regeneration.

Keywords:  3D printing; Bone tissue engineering; Mass transport property; Mechanical property; Osteogenesis; Pore size graded scaffold; Vascularization

DOI:  https://doi.org/10.1016/j.bioactmat.2024.11.024
Front Bioeng Biotechnol. 2024 ;12 1491669

Perspective of 3D culture in medicine: transforming disease research and therapeutic applications.

Chan Hum Park, Jung Ho Park, Yong Joon Suh.

  3D cell culture is gaining momentum in medicine due to its ability to mimic real tissues (in vivo) and provide more accurate biological data compared to traditional methods. This review explores the current state of 3D cell culture in medicine and discusses future directions, including the need for standardization and simpler protocols to facilitate wider use in research.
Purpose: 3D cell culture develops life sciences by mimicking the natural cellular environment. Cells in 3D cultures grow in three dimensions and interact with a matrix, fostering realistic cell behavior and interactions. This enhanced model offers significant advantages for diverse research areas.
Methods: By mimicking the cellular organization and functionalities found in human tissues, 3D cultures provide superior platforms for studying complex diseases like cancer and neurodegenerative disorders. This enables researchers to gain deeper insights into disease progression and identify promising therapeutic targets with greater accuracy. 3D cultures also play a crucial role in drug discovery by allowing researchers to effectively assess potential drugs' safety and efficacy.
Results: 3D cell culture's impact goes beyond disease research. It holds promise for tissue engineering. By replicating the natural tissue environment and providing a scaffold for cell growth, 3D cultures pave the way for regenerating damaged tissues, offering hope for treating burns, organ failure, and musculoskeletal injuries. Additionally, 3D cultures contribute to personalized medicine. Researchers can use patient-derived cells to create personalized disease models and identify the most effective treatment for each individual.
Conclusion: With ongoing advancements in cell imaging techniques, the development of novel biocompatible scaffolds and bioreactor systems, and a deeper understanding of cellular behavior within 3D environments, 3D cell culture technology stands poised to revolutionize various aspects of healthcare and scientific discovery.

Keywords:  3D culture; biomaterial; bioprinting; medicine; scaffold; stem cell

DOI:  https://doi.org/10.3389/fbioe.2024.1491669
J Biomed Mater Res B Appl Biomater. 2025 Jan;113(1): e35525

Template-Assisted Electrospinning and 3D Printing of Multilayered Hierarchical Vascular Grafts.

Moein Zarei, Marek J Żwir, Beata Michalkiewicz, Jarosław Gorący, Miroslawa El Fray.

  Fabricating complex hierarchical structures mimicking natural vessels and arteries is pivotal for addressing problems of cardiovascular diseases. Various fabrication strategies have been explored to achieve this goal, each contributing unique advantages and challenges to the development of functional vascular grafts. In this study, a three-layered tubular structure resembling vascular grafts was fabricated using biocompatible and biodegradable copolymers of poly(butylene succinate) (PBS) using advanced manufacturing techniques. The outer layer was fabricated by template-assisted electrospinning utilizing a 3D-printed scaffold with a precise hexagonal pore design as the template, and the inner layer was coated with gelatin through perfusion. Cellulose nanocrystals (CNCs) were incorporated into electrospun fibers to enhance mechanical properties. The gelatin coating was applied to the lumen using perfusion coating, resembling the inner layer. Integration of 3D-printed structures with electrospun fibers via template-assisted electrospinning and gelatin coating resulted in a seamless multilayered scaffold. Mechanical testing demonstrated robustness, surpassing natural arteries in some aspects, while the gelatin coating significantly reduced liquid leakage, ensuring leak-free functionality. Cytotoxicity assessment confirmed the biocompatibility of processed materials with fibroblast cells, supporting potential for medical applications.

Keywords:  3D printing; multilayered structures; template‐assisted electrospinning; vascular grafts

DOI:  https://doi.org/10.1002/jbm.b.35525
Colloids Surf B Biointerfaces. 2024 Dec 23. pii: S0927-7765(24)00729-X. [Epub ahead of print]248 114470

3D-printed Ti3C2/polycaprolactone composite scaffold with a DOPA-SDF1 surface modified for bone repair.

Yu Han, Li-Hui Sun, Bo Cai, Ming Xia, Chun-Quan Zhu, Dong-Song Li.

  Large bone defects are a major clinical challenge in bone reconstructive surgery. 3D printing is a powerful technology that enables the manufacture of custom tissue-engineered scaffolds for bone regeneration. Electrical stimulation (ES) is a treatment method for external bone defects that compensates for damaged internal electrical signals and stimulates cell proliferation and differentiation. In this study, we propose a simple, reliable, and versatile strategy to prepare multifunctional 3D printed scaffold combined with ES for bone defect therapy. Firstly, scaffolds composed of polycaprolactone (PCL) and Ti3C2 were prepared by 3D printing technology, and then a stromal cell derived factor 1 (SDF1) containing DOPA tag was loaded onto the scaffold surface. Ti3C2 was selected as the electrode component because of its excellent electrical conductivity. The selection of DOPA-modified SDF-1(DOPA-SDF1) can improve the material binding ability and exert long-term stem cell recruitment function. The results show that prepared 3D printed scaffold (DOPA-SDF1@PCL#Ti3C2) has good hydrophilicity, electrical conductivity, antibacterial property, biocompatibility and stem cell recruitment ability. Furthermore, the expression of osteogenic specific genes in scaffold surface cells was significantly increased when pulse ES (PES) treatment was applied. The results of tibial plateau defect repair experiment showed that DOPA-SDF1@PCL#Ti3C2 scaffold can significantly promote the formation of new bone and collagen fibres. When the DOPA-SDF1@PCL#Ti3C2 scaffold was used in combination with PES therapy, the bone defect regeneration rate was further improved. This kind of scaffold could provide a new strategy for promoting the healing of large bone injuries and could expand the application of adjuvant therapy such as PES.

Keywords:  3D-printed scaffold; Bone defect; Electrical stimulation; SDF1; Ti(3)C(2)

DOI:  https://doi.org/10.1016/j.colsurfb.2024.114470
Sci Rep. 2024 12 28. 14(1): 31184

A preliminary study of cell-based bone tissue engineering into 3D-printed β-tricalcium phosphate scaffolds and polydioxanone membranes.

L Pitol-Palin, J Moura, P B Frigério, F R de Souza Batista, S Saska, L J M Oliveira, E Y Matsubara, L Pilatti, D Câmara, N Lizier, A Blay, J A Shibli, R Okamoto.

  Treatment of complex craniofacial deformities is still a challenge for medicine and dentistry because few approach therapies are available on the market that allow rehabilitation using 3D-printed medical devices. Thus, this study aims to create a scaffold with a morphology that simulates bone tissue, able to create a favorable environment for the development and differentiation of osteogenic cells. Moreover, its association with Plenum Guide, through cell-based tissue engineering (ASCs) for guided bone regeneration in critical rat calvarial defects. The manufacturing and characterization of 3D-printed β-TCP scaffolds for experimental surgery was performed. Nine male rats were divided into three groups: β-TCP + PDO membrane (TCP/PG), β-TCP/ASCs + PDO membrane (TCPasc/PG), and β-TCP/ASCs + PDO membrane/ASCs (TCPasc/PGasc). A surgical defect with a 5-mm diameter was performed in the right parietal bone, and the defect was filled with the 3D-printed β-TCP scaffold and PDO membrane with or without ASCs. The animals were euthanized 7, 14, and 30 days after the surgical procedure for histomorphometric and immunolabeling analyses. 3D-printed β-TCP scaffolds were created with a 404 ± 0.0238 μm gyroid macro-pore and, the association to cell-based therapy promotes, especially in the TCPasc/PGasc group, a bone area formation at the defect border region and the center of the defect. The use of 3D-printed β-TCP scaffolds and PDO membranes associated with cell-based therapy could improve and accelerate guided bone regeneration, promoting an increase in osteogenic capacity and reducing the time involved in the bone formation process. Moreover, using ASCs optimized the bioceramics by increasing its osteoinductive and osteoprogenitor capacity and, even with the resorption of the printed scaffold, aided as a scaffold for mesenchymal cell differentiation, as well as in bone tissue formation.

Keywords:  3D-printed scaffolds; Bone regeneration; Cell-based therapy; Polydioxanone; Tissue engineering

DOI:  https://doi.org/10.1038/s41598-024-82334-6
Int J Pharm. 2024 Dec 26. pii: S0378-5173(24)01375-9. [Epub ahead of print]670 125141

3D-printed cannabidiol hollow suppositories for treatment of epilepsy.

Meng Wei, Dongdong Liu, Hua Xie, Yingbao Sun, Yubao Fang, Lina Du, Yiguang Jin.

  Cannabidiol (CBD) is widely used to alleviate the syndromes of epilepsy. However, the marketed oral CBD formulation has the prominent first-pass effect. Here, a cannabidiol-loaded hollow suppository (CHS) was developed using three-dimensional (3D) printing technology. CHS was assembled with an inner supporting spring and an outer CBD-loaded curved hollow shell. The spring was prepared using fused deposition modeling 3D printing with thermoplastic urethane filaments followed by splitting. The shell was prepared with a 3D-printed metal mold filled with the mixture of CBD, polyvinyl alcohol, and polyethylene glycol. CHS slowly in vitro released CBD for 5 h and achieved the systemic delivery of CBD. The high in vitro and in vivo safety of CHS was demonstrated. Epilepsy rat models were established by lithium-pilocarpine dosing. Locally administered CHS greatly alleviated the damage to brains and reduced inflammation. Moreover, CBD obviously improved the abundance and composition of gut microbiota and the abundance of beneficial bacteria, including Lachnoclostridium and Akkermansia. Personalized CHS is a promising medication for the treatment of epilepsy.

Keywords:  3D printing; Cannabidiol; Epilepsy; Suppository

DOI:  https://doi.org/10.1016/j.ijpharm.2024.125141
Int J Biol Macromol. 2024 Dec 30. pii: S0141-8130(24)10157-2. [Epub ahead of print]293 139346

A 3D bioprinted potential colorectal tumor model based on decellularized matrix/gelatin methacryloyl/nanoclay/sodium alginate hydrogel.

Xinyue Liu, Yan Shu, Jingjing Zhu, Huan Fang, Ya Su, Hailin Ma, Bing Li, Jie Xu, Yuen Yee Cheng, Bo Pan, Kedong Song.

  Colorectal cancer (CRC) is now the third most common cancer worldwide. However, the development cycle for anticancer drugs is lengthy and the failure rate is high, highlighting the urgent need for new tumor models for CRC-related research. The decellular matrix (dECM) offers numerous cell adhesion sites, proteoglycan and cytokines. Notably, porcine small intestine is rich in capillaries and lymphatic capillaries, which facilitates nutrient absorption. This study, we utilized dECM, along with methylacryloyl gelatin (GelMA), sodium alginate (SA) and nanoclay (NC) to create a hydrogel scaffold through 3D extrusion bioprinting. Human CRC cells (HCT8) were seeded onto the scaffold and their drug resistance was tested using 5-fluorouracil (5-FU). Our findings indicate that dECM enhances the hydrophilic properties, mechanical strength and biocompatibility of the scaffold. Furthermore, compared to traditional two-dimensional (2D) models, the three-dimensional (3D) scaffold supports the long-term growth of tumor spheres. After 2 days of 5-FU treatment, the cell survival rate reaches 88.06 ± 0.51 %. This suggests that our scaffold provides a promising alternative platform for in vitro research on cancer mechanisms, anti-cancer drug screening and new drug development.

Keywords:  3D extrusion bioprinting; 3D tumor model; Colorectal cancer; Decellularized matrix; Gelatin methacryloy

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139346
BMC Musculoskelet Disord. 2024 Dec 30. 25(1): 1090

Application of 3D-printed porous prosthesis for the reconstruction of infectious bone defect with concomitant severe soft tissue lesion: a case series of 13 cases.

Zhuo Chen, Yiyuan Yang, Bingchuan Liu, Xingcai Li, Yun Tian.

   BACKGROUND: Treating infectious bone defects combined with large soft-tissue lesions poses significant clinical challenges. Herein, we introduced a modified two-stage treatment approach involving the implantation of 3D-printed prostheses and flap repair to treat large segmental infectious tibial bone defects.
METHOD: We conducted a retrospective study of 13 patients treated at our center between April 2018 and March 2022 for tibial infections owing to posttraumatic infection and chronic osteomyelitis combined with soft tissue defects. The average defect length was 14.0 cm (range, 5.7-22.9 cm). The flap area ranged from 14 × 5 to 15 × 8 + 25 × 15 cm. Sural neurocutaneous, lesser saphenous neurocutaneous, and local fasciocutaneous flaps were used to repair the skin defects. In the second stage, 3D-printed prostheses were designed and implanted. Union rate, complications, and functional outcomes were assessed at the final follow-up.
RESULT: The average follow-up period was 31.1 months (range, 17-47 months), with an average interval of 208.1 days (range, 139-359 days) between the two stages. According to our criteria, 7 of the 13 patients achieved radiographic healing without intervention. Two patients developed prosthesis-related complications and underwent revision surgery. Two patients experienced recurrent infections leading to prosthesis removal and debridement surgery, with the infection ultimately eradicated in one and the other undergoing amputation. Three patients experienced noninfectious flap-related complications, however, all eventually healed through surgical intervention.
CONCLUSION: The use of 3D-printed porous titanium prostheses combined with flap soft-tissue repair for the treatment of infectious tibial bone defects did not increase the rate of infection recurrence and provided good functional recovery, offering more options for the treatment of infectious bone defects.

Keywords:  3D Printed prosthesis; Chronic osteomyelitis; Flap transfer; Infectious bone defects; Soft tissue lesion; Tibial bone defect

DOI:  https://doi.org/10.1186/s12891-024-08248-6
Mikrochim Acta. 2024 12 30. 192(1): 42

Cutting-edge 3D printing in immunosensor design for early cancer detection.

Sachin Kothawade, Vijaya Padwal.

  Cancer is a major cause of death globally, and early detection is a key to improving outcomes. Traditional diagnostic methods have limitations such as being invasive and lacking sensitivity. Immunosensors, which detect cancer biomarkers using antibodies, offer a solution with high sensitivity and selectivity. When combined with 3D printing, these immunosensors can be customized to detect specific cancer markers, creating rapid, cost-effective, and scalable diagnostic tools. The article reviews the principles behind immunosensors, different 3D fabrication methods such as Fused Deposition Modeling (FDM) and Stereolithography (SLA), and discusses how functionalization strategies, such as surface modifications, can enhance the sensitivity of these devices. The integration of 3D printing allows for the creation of complex sensor structures, offering advantages such as customization, rapid prototyping, and multi-material printing. These advancements make immunosensors arrays highly promising for early cancer detection, tumor profiling, and personalized medicine. The article also explores challenges like scalability, material biocompatibility, and the need for clinical validation. Future perspectives suggest the potential of integrating nanomaterials, multiplexed detection, and wearable technology to further improve the performance and accessibility of these diagnostic tools.

Keywords:  3D printing; Biomarker detection; Cancer diagnostics; Immunosensor arrays; Personalized medicine; Tumor profiling

DOI:  https://doi.org/10.1007/s00604-024-06880-6