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Bone Tissue Engineering: Opportunities and Challenges
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Bone Tissue Engineering: Opportunities and Challenges

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 3018

Special Issue Editors

Dr. Elisa Mazzoni

E-Mail Website
Guest Editor
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy
Interests: stem cells differentiation; material; scaffold; bone; tissue regeneration; signalling; infection; tumour
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Rosa Iaquinta

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
Interests: regenerative medicine; biomaterials; stem cells; bone tissue engineering; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tissue engineering (TE) aims to repair and regenerate tissues damaged by injury or disease. To this end, bone grafting has emerged as a viable treatment modality. Biomaterials play a key role in this reparative strategy. The burgeoning science of nanomaterials as nanomedicines is growing. Innovative materials can be functionalized with several bioactive molecules and ions, allowing them to be incorporated into and improve different scaffolds used in regenerative medicine. Novel biological therapies that can effectively treat bone fracturing or degeneration are of great significance in regenerative medicine. In addition, mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and umbilical cord (UC-MSCs) show considerable promise for use in bone repair. The microenvironment, including that of the immune system, influences the state of stem cells in the context of tissue repair and regeneration of bone tissue. Although extensive strides have been made in our collective understanding of the processes governing bone and tissue regeneration within the microenvironment, effective clinical translation of these mechanisms remains a challenge. These materials, both alone and in combination with MSCs, may be promising in tissue regeneration.

Dr. Elisa Mazzoni
Dr. Maria Rosa Iaquinta
Guest Editors

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Keywords

  • material
  • biocompatibility
  • scaffold
  • regeneration
  • bone
  • osteoinductivity
  • tissue
  • stem cells
  • microenvironment processes
 

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Published Papers (4 papers)

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Research

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24 pages, 3197 KiB  
Article
Secretome Release During In Vitro Bone Marrow-Derived Mesenchymal Stem Cell Differentiation Induced by Bio-Oss® Collagen Material
by Maria Rosa Iaquinta, Raffaella De Pace, Assia Benkhalqui, Antonio D’Agostino, Lorenzo Trevisiol, Alessia Finotti, Giulia Breveglieri, Mauro Tognon, Fernanda Martini and Elisa Mazzoni
Int. J. Mol. Sci. 2025, 26(8), 3807; https://doi.org/10.3390/ijms26083807 - 17 Apr 2025
Viewed by 210
Abstract
Bone diseases represent a growing healthcare challenge due to population aging and lifestyle changes. Although bone has a natural regenerative capacity, approximately 10% of fractures fail to heal properly, requiring advanced therapeutic approaches. Bone tissue engineering (BTE) has advanced the use of osteoinductive [...] Read more.
Bone diseases represent a growing healthcare challenge due to population aging and lifestyle changes. Although bone has a natural regenerative capacity, approximately 10% of fractures fail to heal properly, requiring advanced therapeutic approaches. Bone tissue engineering (BTE) has advanced the use of osteoinductive and osteoconductive biomaterials to support bone regeneration. Among them, Bio-Oss® Collagen, a composite of bovine hydroxyapatite and collagen, has shown excellent biocompatibility and bioactivity properties. This study analyzes the effect of Bio-Oss® Collagen on human bone marrow-derived mesenchymal stem cells (hBMSCs), assessing its osteoinductive and immunomodulatory potential. After 7 days of culture, the biomaterial modulated the expression of key genes involved in osteogenesis and chondrogenesis, which are known for their role in bone formation and maturation. At the same time, a downregulation of genes associated with bone resorption was observed. Secretome analysis revealed a controlled release of pro-regenerative cytokines, suggesting a role of the biomaterial in modulating inflammation to promote bone regeneration. Furthermore, immunofluorescence confirmed the high expression of osteocalcin and osteopontin, which are key markers of bone mineralization. These findings indicate that Bio-Oss® Collagen supports osteogenesis and modulates the immune response, creating a microenvironment favorable for bone regeneration. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Opportunities and Challenges)
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17 pages, 3481 KiB  
Article
Targeting Age-Related Impaired Bone Healing: ZnO Nanoparticle-Infused Composite Fibers Modulate Excessive NETosis and Prolonged Inflammation in Aging
by Do-Yeun Kim, Jeong-Hyun Ryu, Jae-Hyung Kim, Eun-Hye Lee, Jeong-Hwa Baek and Kyung Mi Woo
Int. J. Mol. Sci. 2024, 25(23), 12851; https://doi.org/10.3390/ijms252312851 - 29 Nov 2024
Viewed by 1003
Abstract
Bone defects present significant challenges in clinical contexts, particularly among the elderly, and are often linked to altered innate immune responses; however, underlying mechanisms remain to be understood. This study investigates immune changes in early bone healing in aged mice, emphasizing the effects [...] Read more.
Bone defects present significant challenges in clinical contexts, particularly among the elderly, and are often linked to altered innate immune responses; however, underlying mechanisms remain to be understood. This study investigates immune changes in early bone healing in aged mice, emphasizing the effects of zinc in modulating inflammatory processes. By exploring the role of zinc and NETosis in this process, we seek to develop novel therapeutic strategies that could improve bone repair in aging populations. Critical-sized calvarial bone defects were induced in young (8-week-old) and aged (18-month-old) mice, with RNA sequencing analysis. Zinc oxide nanoparticle-infused polycaprolactone (ZnPCL) scaffolds were then fabricated using electrospinning, and their effects on intracellular zinc levels, NETosis, M2 polarization, and bone formation were assessed through in vitro and in vivo experiments. In aged mice, bone healing was delayed, inflammation was prolonged, and NETosis was excessive. RNA sequencing identified alterations in zinc ion transport genes, alongside excessive NETosis. Aged mouse neutrophils exhibited low intracellular zinc levels. ZnPCL fibers effectively reduced NETosis and inflammation, promoted M2 macrophage polarization, and enhanced new bone formation, thereby improving bone healing in aged mice. This study demonstrates that ZnO nanoparticle-infused biomaterials, ZnPCL, effectively deliver zinc to neutrophils, reduce NETosis, promote M2 polarization, and enhance bone healing in aged mice. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Opportunities and Challenges)
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Graphical abstract

18 pages, 5383 KiB  
Article
Bone Regenerative Effect of Injectable Hypoxia Preconditioned Serum-Fibrin (HPS-F) in an Ex Vivo Bone Defect Model
by Jun Jiang, Lynn Röper, Finja Fuchs, Marc Hanschen, Sandra Failer, Sarah Alageel, Xiaobin Cong, Ulf Dornseifer, Arndt F. Schilling, Hans-Günther Machens and Philipp Moog
Int. J. Mol. Sci. 2024, 25(10), 5315; https://doi.org/10.3390/ijms25105315 - 13 May 2024
Cited by 2 | Viewed by 1282
Abstract
Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. [...] Read more.
Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Opportunities and Challenges)
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Review

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54 pages, 4610 KiB  
Review
Evolution in Bone Tissue Regeneration: From Grafts to Innovative Biomaterials
by Domingo Cesar Carrascal-Hernández, Juan Pablo Martínez-Cano, Juan David Rodríguez Macías and Carlos David Grande-Tovar
Int. J. Mol. Sci. 2025, 26(9), 4242; https://doi.org/10.3390/ijms26094242 - 29 Apr 2025
Abstract
Bone defects caused by various traumas and diseases such as osteoporosis, which affects bone density, and osteosarcoma, which affects the integrity of bone structure, are now well known. Given this situation, several innovative research projects have been reported to improve orthopedic methods and [...] Read more.
Bone defects caused by various traumas and diseases such as osteoporosis, which affects bone density, and osteosarcoma, which affects the integrity of bone structure, are now well known. Given this situation, several innovative research projects have been reported to improve orthopedic methods and technologies that positively contribute to the regeneration of affected bone tissue, representing a significant advance in regenerative medicine. This review article comprehensively analyzes the transition from existing methods and technologies for implants and bone tissue regeneration to innovative biomaterials. These biomaterials have been of great interest in the last decade due to their physicochemical characteristics, which allow them to overcome the most common limitations of traditional grafting methods, such as the availability of biomaterials and the risk of rejection after their application in regenerative medicine. This could be achieved through an exhaustive study of the applications and properties of various materials with potential applications in regenerative medicine, such as using magnetic nanoparticles and hydrogels sensitive to external stimuli, including pH and temperature. In this regard, this review article describes the most relevant compounds used in bone tissue regeneration, promoting the integration of these biomaterials with the affected area’s bone structure, thereby allowing for regeneration and preventing amputation. Additionally, the types of interactions between biomaterials and mesenchymal stem cells and their effects on bone tissue are discussed, which is critical for developing biomaterials with optimal regenerative properties. Furthermore, the mechanisms of action of the various biomaterials that enhance osteoconduction and osteoinduction, ensuring the success of orthopedic therapies, are analyzed. This enables the treatment of bone defects tailored to each patient’s condition, thereby avoiding limb amputation. Consequently, a promising future for regenerative medicine is emerging, with various therapies that could revolutionize the management of bone defects, offering more efficient and safer solutions. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Opportunities and Challenges)
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