bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–06–04
five papers selected by
Seerat Maqsood, University of Teramo



  1. Ann Biomed Eng. 2023 Jun 01.
      Bioprinting is an innovative and emerging technology of additive manufacturing (AM) and has revolutionized the biomedical sector by printing three-dimensional (3D) cell-laden constructs in a precise and controlled manner for numerous clinical applications. This approach uses biomaterials and varying types of cells to print constructs for tissue regeneration, e.g., cardiac, bone, corneal, cartilage, neural, and skin. Furthermore, bioprinting technology helps to develop drug delivery and wound healing systems, bio-actuators, bio-robotics, and bio-sensors. More recently, the development of four-dimensional (4D) bioprinting technology and stimuli-responsive materials has transformed the biomedical sector with numerous innovations and revolutions. This issue also leads to the exponential growth of the bioprinting market, with a value over billions of dollars. The present study reviews the concepts and developments of 3D and 4D bioprinting technologies, surveys the applications of these technologies in the biomedical sector, and discusses their potential research topics for future works. It is also urged that collaborative and valiant efforts from clinicians, engineers, scientists, and regulatory bodies are needed for translating this technology into the biomedical, pharmaceutical, and healthcare systems.
    Keywords:  3D bioprinting; 4D bioprinting; Additive manufacturing; Biomedical applications; Tissue engineering
    DOI:  https://doi.org/10.1007/s10439-023-03243-9
  2. Regen Biomater. 2023 ;10 rbad037
      Bone tissue engineering (BTE) has been proven to be an effective method for the treatment of bone defects caused by different musculoskeletal disorders. Photocrosslinkable hydrogels (PCHs) with good biocompatibility and biodegradability can significantly promote the migration, proliferation and differentiation of cells and have been widely used in BTE. Moreover, photolithography 3D bioprinting technology can notably help PCHs-based scaffolds possess a biomimetic structure of natural bone, meeting the structural requirements of bone regeneration. Nanomaterials, cells, drugs and cytokines added into bioinks can enable different functionalization strategies for scaffolds to achieve the desired properties required for BTE. In this review, we demonstrate a brief introduction of the advantages of PCHs and photolithography-based 3D bioprinting technology and summarize their applications in BTE. Finally, the challenges and potential future approaches for bone defects are outlined.
    Keywords:  bone defect; bone regeneration; bone tissue engineering; photocrosslinkable hydrogels; photolithography 3D bioprinting
    DOI:  https://doi.org/10.1093/rb/rbad037
  3. Int J Pharm. 2023 May 31. pii: S0378-5173(23)00513-6. [Epub ahead of print] 123093
      Bone repair and tissue-engineering (BTE) approaches require novel biomaterials to produce scaffolds with required structural and biological characteristics and enhanced performances with respect to those currently available. In this study, PCL/INU-PLA hybrid biomaterial was prepared by blending of the aliphatic polyester poly(ε-caprolactone) (PCL) with the amphiphilic graft copolymer Inulin-g-poly(D,L)lactide (INU-PLA) synthetized from biodegradable inulin (INU) and poly(lactic acid) (PLA). The hybrid material was suitable to be processed using fused filament fabrication 3D printing (FFF-3DP) technique rendering macroporous scaffolds. PCL and INU-PLA were firstly blended as thin films through solvent-casting method, and then extruded by hot melt extrusion (HME) in form of filaments processable by FFF-3DP. The physicochemical characterization of the hybrid new material showed high homogeneity, improved surface wettability/hydrophilicity as compared to PCL alone, and right thermal properties for FFF process. The 3D printed scaffolds exhibited dimensional and structural parameters very close to those of the digital model, and mechanical performances compatible with the human trabecular bone. In addition, in comparison to PCL, hybrid scaffolds showed an enhancement of surface properties, swelling ability, and in vitro biodegradation rate. In vitro biocompatibility screening through hemolysis assay, LDH cytotoxicity test on human fibroblasts, CCK-8 cell viability, and osteogenic activity (ALP evaluation) assays on human mesenchymal stem cells showed favorable results.
    Keywords:  3D printing; Bone Tissue Engineering; Fused Filament Fabrication; Hybrid 3D printed scaffolds; Hybrid biodegradable material; Inulin-g-poly(D,L)lactide; poly(ε-caprolactone)
    DOI:  https://doi.org/10.1016/j.ijpharm.2023.123093
  4. Int J Bioprint. 2023 ;9(2): 658
      In order to generate a high-performance personalized biological fixation plate with matching mechanical properties and biocompatibility, reverse reconstruction and fracture reduction of a femur were performed by combining reverse and forward approaches, and the surface was extracted according to the installation position of the plate to complete plate modeling by shifting, thickening, and performing other operations. Subsequently, topology optimization and three-dimensional (3D) printing were performed, and the properties of the manufactured plate were probed. The results showed that the maximum displacement of the plate was 4.13 mm near the femoral head, the maximum stress was 5.15e2 MPa on both sides of the plate across its entire length, and the stress concentration decreased following topology optimization. The plate with optimized topology and filled with porous structure has a good filling effect. The final mass of the H-shaped plate was 12.05 g, while that of the B-shaped plate was 11.05 g, which dropped by 20.93% and 27.49%, respectively, compared with the original plate. The surface of the 3D-printed plate was bright and new, with a clear pore structure and good lap joint. The B-shaped and H-shaped plates were closely dovetailed with the host bone, which met the assembly requirements. This lays a foundation for the direct application of a high-performance personalized biological fixation plate.
    Keywords:  Bone plate; Forming quality; Selective laser melting; Simulation analysis; Topological optimization
    DOI:  https://doi.org/10.18063/ijb.v9i2.658
  5. J Cell Mol Med. 2023 Jun 01.
      The preparation of biodegradable scaffolds loaded with cells and cytokine is a feature of tissue-engineered skin. IPSCs-based tissue-engineered skin treatment for wound repair is worth exploring. Healthy human skin fibroblasts were collected and reprogrammed into iPSCs. After gene modification and induction, CK19+ /Integrinβ1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP were obtained and identified by a combination of immunofluorescence and RT-qPCR. Astragalus polysaccharide-containing 3D printed degradable scaffolds were prepared and co-cultured with VEGF165 gene-modified iPS-HFSCsGFP , and the biocompatibility and spatial structure of the tissue-engineered skin was analysed by cell counting kit-8 (CCK8) assay and scanning electron microscopy. Finally, the tissue-engineered skin was transplanted onto the dorsal trauma of nude mice, and the effect of tissue-engineered skin on the regenerative repair of total skin defects was evaluated by a combination of histology, immunohistochemistry, immunofluorescence, RT-qPCR, and in vivo three-dimensional reconstruction under two-photon microscopy. CK19+ /Integrinβ1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP , close to the morphology and phenotype of human-derived hair follicle stem cells, were obtained. The surface of the prepared 3D printed degradable scaffold containing 200 μg/mL astragalus polysaccharide was enriched with honeycomb-like meshwork, which was more conducive to the proliferation of the resulting cells. After tissue-engineered skin transplantation, combined assays showed that it promoted early vascularization, collagen and hair follicle regeneration and accelerated wound repair. VEGF165 gene-modified iPS-HFSCsGFP compounded with 3D printed degradable scaffolds containing 200 μg/mL astragalus polysaccharide can directly and indirectly participate in vascular, collagen, and hair follicle regeneration in the skin, achieving more complete structural and functional skin regenerative repair.
    Keywords:  3D printed degradable scaffold; astragalus polysaccharide; hair follicle stem cells; induced pluripotent stem cells; regeneration and repair; skin defect
    DOI:  https://doi.org/10.1111/jcmm.17800