Functionalization Strategies of Chitosan-Based Scaffolds with Growth Factors for Bone Regeneration: A Systematic
Jan Kiryk1, Mateusz Michalak2, Zuzanna Majchrzak2
1Dental Surgery Department, Wroclaw Medical University, Krakowska 26, 50-425 Wroclaw, Poland.
Abstract:
Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search was conducted in July 2025 across the PubMed, Scopus, and Web of Science databases. Search terms included combinations of (chitosan scaffold) AND (growth factor OR BMP-2 OR VEGF OR FGF OR TGF-beta OR periostin OR PDGF OR IGF-1 OR EGF OR ANG-1 OR ANG-2 OR GDF-5 OR SDF-1 OR osteopontin). The study selection process followed PRISMA 2020 guidelines and the PICO framework. Out of 367 records, 226 were screened, and 17 studies met the eligibility criteria for qualitative analysis. BMP-2 was the most frequently investigated growth factor, studied in both in vitro and in vivo models, with rats and rabbits as the most common animal models. Scaffold compositions varied, incorporating hydroxyapatite, heparin, polyethylene glycol diacrylate, octacalcium phosphate-mineralized graphene, silk fibroin, and aloe vera. Growth factors were introduced using diverse methods, including microspheres, chemical grafting, covalent coupling, protein carriers, and nanohydroxyapatite mesopores. Most studies reported enhanced bone regeneration, although differences in models, scaffold composition, and delivery methods preclude definitive conclusions. The addition of growth factors generally improved osteoblast proliferation, angiogenesis, bone density, and expression of osteogenic markers (RunX2, COL1, OPN, OCN). Combining two bioactive agents further amplified osteoinduction and vascularization. Sustained-release systems, particularly those using heparin or hydroxyapatite, prolonged biological activity and improved regenerative outcomes. In conclusion, functionalization of chitosan-based scaffolds with growth factors shows promising potential for bone regeneration. Controlled-release systems and combinations of different bioactive molecules may offer synergistic effects on osteogenesis and angiogenesis. Further research should focus on optimizing scaffold compositions and delivery methods to tailor bioactive agent release for specific clinical applications.
Insights
Chitosan scaffolds combined with growth factors show promise for bone regeneration, enhancing osteogenesis and angiogenesis. Optimized delivery systems and combinations of bioactive agents may improve outcomes for clinical applications.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Bioactive agents stimulate osteogenesis, angiogenesis, and cell proliferation, offering therapeutic potential for bone regeneration.
- Chitosan-based scaffolds are widely explored for bone regeneration due to their biocompatibility and biodegradability.
Purpose of the Study:
- To systematically review strategies for applying chitosan-based scaffolds with growth factors for enhanced bone regeneration.
- To evaluate the impact of different growth factors and scaffold compositions on regenerative outcomes.
Main Methods:
- A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases.
- Included studies analyzed chitosan scaffolds functionalized with various growth factors (e.g., BMP-2, VEGF) using diverse delivery methods.
- PRISMA 2020 guidelines and PICO framework were followed for study selection and qualitative analysis of 17 eligible studies.
Main Results:
- BMP-2 was the most common growth factor investigated across in vitro and in vivo models.
- Scaffold compositions varied, incorporating materials like hydroxyapatite and silk fibroin, with growth factors delivered via microspheres or chemical grafting.
- Most studies reported enhanced bone regeneration, improved osteoblast proliferation, angiogenesis, and osteogenic marker expression, especially with sustained-release systems and combined bioactive agents.
Conclusions:
- Functionalizing chitosan-based scaffolds with growth factors demonstrates significant potential for bone regeneration.
- Controlled-release systems and combinations of bioactive molecules can provide synergistic effects on osteogenesis and angiogenesis.
- Further research is needed to optimize scaffold design and delivery methods for tailored clinical applications.
