Biofabrication Technologies: Novel Tools for More Effective Personalized Medicine and Regenerative Therapies

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 6134

Editors


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Guest Editor
Research Center E. Piaggio and Department of Information Engineering, University of Pisa, 56126 Pisa, Italy
Interests: bioengineering; biomedical engineering; tissue engineering; microfabrication; bioreactors for tissue culture; microactuators fabrication
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Department of Pharmacy, Università di Pisa, Pisa, Italy
Interests: microRNA; anticancer drugs; circulating biomarkers; marine compounds; natural compounds; melanoma
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: phytochemistry; isolation and characterization of natural compounds; bioactivity of natural compounds on skin disease models

Special Issue Information

Dear Colleagues,

Driven by innovations in engineering, biology, and biomaterials, as well as by its own potential, the field of biofabrication has evolved rapidly in the last two decades, creating marvelous opportunities and enabling new research directions within personalized biomedicine and regenerative therapies. Because the impact of this research field has been and continues to be enormous, this Special Issue invites scientists working at universities, research institutes, laboratories, and in different industries to discuss state-of-the-art research and the latest developments in the biofabrication technologies used to define novel approaches in regenerative and/or personalized medicine, which will enable us to overcome the limitations of animal model validation and to speed up their clinical application, while taking into account their quality and regulation.

In this Special Issue, we welcome full articles, short communications, and reviews that highlight the recent findings that have broadened the horizons of biofabrication, including, but not limited to, new bioinks, new biofabrication approaches and technological advancements, progress in the translation of biofabrication technologies from bench to bedside, novel 3D models in regenerative and personalized medicine, non-destructive methods used for characterization, and achievements in the regulatory field.

It is our pleasure to invite submissions to this Special Issue of Bioengineering.

Prof. Dr. Giovanni Vozzi
Prof. Dr. Paola Nieri
Dr. Mauro Di Stasi
Guest Editors

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Keywords

  • biodegradable polymers
  • biocompatible polymers
  • biomedical applications
  • biomaterials
  • renewable biomaterials
  • tissue engineering
  • regenerative medicine
  • biofabrication and bioprinting
  • personalized medicine
  • 3D tissue models

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Published Papers (3 papers)

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Research

16 pages, 5371 KB  
Article
Histological Study of a Novel 3D-Printed Hydroxyapatite/PLGA Bone Graft in the Regeneration of Critical-Sized Long Bone Defects
by Marijana Popović Bajić, Smiljana Paraš, Milutin Mićić, Božana Petrović, Vladimir Biočanin, Slavoljub Živković, Marija Živković, Damjana Drobne and Vukoman Jokanović
Bioengineering 2026, 13(4), 394; https://doi.org/10.3390/bioengineering13040394 - 28 Mar 2026
Viewed by 2081
Abstract
Critical-sized bone defects pose significant challenges in orthopedic surgery. The introduction of 3D printing technology in bone grafting offers a promising solution by creating customized grafts that mimic the natural bone structure. This study aimed to reconstruct long-segment bone defects in the rabbit [...] Read more.
Critical-sized bone defects pose significant challenges in orthopedic surgery. The introduction of 3D printing technology in bone grafting offers a promising solution by creating customized grafts that mimic the natural bone structure. This study aimed to reconstruct long-segment bone defects in the rabbit radius using a 3D-printed material composed of hydroxyapatite (HAP) and poly(lactide-co-glycolide) (PLGA), referred to as ALBO-OS, and to evaluate its potential to support bone healing without the use of stem cells or growth factors. Six rabbits underwent computed tomography scanning to create patient-specific 3D models of the radius. Custom-designed ALBO-OS implants were 3D-printed and used to fill segmental defects corresponding to one-third of the bone length in each rabbit, created by osteotomy. Over a 12-week observation period, graft integration, osteointegration, and overall bone regeneration were assessed through histological and histomorphometric analyses. The implanted scaffolds demonstrated encouraging bone healing, with significant bone regeneration observed within the defect areas. Histological evaluation revealed significant new bone formation and vascularization, with minimal inflammatory response. The findings demonstrated the potential of 3D-printed HAP/PLGA-based materials as a promising strategy for the reconstruction of large bone defects, eliminating the need for exogenous biological agents. Full article
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15 pages, 2974 KB  
Article
Augmenting Bone Formation by Implanting Dedifferentiated Fat Cell-Loaded Cotton-like Graft Materials in a Rat Bone Defect Model
by Jin Inoue, Tomohiko Kazama, Takahisa Okubo, Daisuke Akita, Yoshinori Arai, Yoshiyuki Hagiwara, Koichiro Kano, Masaki Honda and Taro Matsumoto
Bioengineering 2025, 12(12), 1364; https://doi.org/10.3390/bioengineering12121364 - 16 Dec 2025
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Abstract
Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal [...] Read more.
Bone graft materials frequently employed in dental implant placement procedures, including hydroxyapatite and β-tricalcium phosphate (β-TCP), are typically granular in form, which complicates their manipulation and contributes to extended treatment durations. A tissue engineering approach utilizing readily manageable biomaterials in conjunction with mesenchymal stem cells (MSCs) represents the most promising approach in dentistry. This study assessed the bone-augmenting capacity at bone defect sites in inbred rats by seeding dedifferentiated fat (DFAT) cells onto a cotton-like bone graft scaffold composed of β-TCP and poly(L-lactic-co- glycolide) (PLGA), which was subsequently wrapped around titanium. As a control, cotton-like bone graft material without cells was used and wrapped around and transplanted. Four weeks post-implantation, computed tomography (CT) images of the DFAT group revealed a 1.25-fold enhancement in hard tissue formation compared to the control group. Histological analysis revealed compact structure in a dark red color surrounding the cotton-like bone graft material was observed on the titanium surface of DFAT group. Histomorphometric analysis revealed that the amount of hard tissue generated in the DFAT group was approximately 2.5 times higher than that observed in the control group. Moreover, this mineralized tissue demonstrated properties analogous to those observed in cortical bone. Collectively, these findings indicate that the composite of DFAT cells and cotton-like bone graft material holds potential for bone augmentation applications and represents a promising approach for regenerative therapies within the orofacial region. Full article
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21 pages, 10700 KB  
Article
A 3D ColMA-Based Tenogenic Microenvironment Unveils the Behavior of Tendon Stem/Progenitor Cells (TSPCs) from Tendinopathic Surgical Explants
by Giacomo Cortella, Erwin Pavel Lamparelli, Joseph Lovecchio, Emanuele Giordano, Nicola Maffulli and Giovanna Della Porta
Bioengineering 2025, 12(12), 1337; https://doi.org/10.3390/bioengineering12121337 - 8 Dec 2025
Cited by 4 | Viewed by 2409
Abstract
Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it [...] Read more.
Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it under perfusion to establish a tenogenic microenvironment in vitro. Pathological human Tendon Stem/Progenitor Cells (hTSPCs) derived from tendinopathic surgical explants were encapsulated to investigate their impaired extracellular matrix (ECM) deposition and associated pro-inflammatory signaling. GDF-5-loaded nanoparticles (average diameter 140 ± 40 nm) were fabricated via microfluidic-assisted nanoprecipitation and homogeneously incorporated within the ColMA synthetic ECM to enable sustained growth factor release. Continuous perfusion culture (1 mL/min) ensured efficient mass transfer and supported cell viability above 70% over 21 days. Pathological hTSPCs exhibited impaired ECM remodeling, characterized by the absence of type I collagen and a 2.56-fold increase in type III collagen at day 7, indicative of a fibrotic-like phenotype. Western blot densitometry demonstrated a 5.31-fold elevation in secreted tenomodulin at day 14, while ECM analysis verified a type III to type I collagen ratio of 4.5. In addition, a markedly pro-inflammatory cytokine profile was observed, with elevated secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) from day 7 onward, consistent with the chronic inflammatory status of cells derived from pathological tendon tissues. This modular 3D platform represents a robust in vitro model for mechanistic studies and the advancement of personalized regenerative strategies targeting chronic tendon disorders. Full article
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