When it comes to healing broken bones, the human body is truly remarkable. Unlike many other organ systems that have lost the ability for tissue repair, the skeletal system is constantly undergoing a remodeling process with osteoclasts breaking down bone and osteoblasts building new bone. With this machinery already in place, the body immediately starts the healing process when a bone fracture occurs. Initially, a blood clot forms around the break, then a soft callus made of collagen forms, and eventually the soft callus is replaced by a hard callus of new bone. Sometimes, our bodies need extra help to speed up and improve bone repair, especially if the injury is severe or if healing ability is impaired due to age or disease.
Polysaccharides, nature’s very own versatile, sugar-based molecules, are revolutionizing the way we think about bone healing. In this post, we’ll explore the fascinating ways in which polysaccharides are being used to craft the perfect microenvironment for bone repair. From natural scaffolds to controlled drug release, these carbohydrates are paving a new way for regenerative medicine.
Understanding Polysaccharides and Bone Healing
Polysaccharides are long chains of carbohydrate molecules found in abundance in nature. They serve a variety of purposes, from energy storage (like starch and glycogen) to providing structural support (like cellulose and chitin). In bone repair, polysaccharides have shown remarkable promise as building blocks to create biomaterials that mimic the natural environment of bones, supporting cell growth and mineralization.
The bone microenvironment is a dynamic and complex biological and structural system that consists of cells (osteocytes, osteoblasts, and osteoclasts), a matrix phase (calcium phosphate in the form of hydroxyapatite crystals with organic collagen), and a soluble phase consisting of cytokines and/or growth factors. Successful bone regeneration depends on having the right microenvironment to facilitate cellular communication and migration, promote bone growth, and prevent infection. This is where polysaccharides are important, providing scaffolds, growth factor delivery, and support for cells involved in bone regeneration. (Hao et al., 2023) (Lu et al., 2017)
Crafting Scaffolds with Polysaccharides
In terms of tissue engineering, scaffolds are three-dimensional structures that serve as templates to guide bone regeneration. Polysaccharides such as Osteo-P® BGS (a hyper-crosslinked carbohydrate polymer) are ideal candidates for bone regeneration scaffolds. Here’s why:
1. Biocompatibility: Polysaccharides are naturally biocompatible, meaning they can interact with the body’s cells without triggering an immune response. This makes them excellent materials for use in biomedical applications.
2. Bioactivity: Many polysaccharides are bioactive, meaning they can interact with cells to promote important functions like cell adhesion and proliferation. Some polysaccharides (example, hyaluronic acid) attract mesenchymal stem cells, which are crucial for bone regeneration.
3. Customizable Properties: With chemical modification, researchers can tune the mechanical properties, degradation rate, and biological activity of polysaccharide scaffolds to meet specific needs for bone regeneration.
Polysaccharides and Controlled Drug Delivery
Another way polysaccharides aid in bone repair is through controlled drug delivery. Bone repair requires specific signals in the form of growth factors or drugs that promote healing, in addition to the scaffold for cells to grow on. Bone morphogenetic protein-2 (BMP2), platelet-derived growth factor (PDGF-BB), and vascular endothelial growth factor (VEGF) are some of the primary growth factors involved in bone regeneration.
BMP-2 stimulates the differentiation of mesenchymal stem cells (MSCs) to form osteocytes, osteoblasts, and chondrocytes; thus, promoting the growth and development of bone and cartilage. VEGF promotes angiogenesis during the inflammatory phase, along with stimulating osteogenesis and osteoclastogenesis during the bone repair phase. PDGF-BB is secreted by osteoclast precursors in the bone marrow to promote differentiation of MSC to osteoblasts for bone deposition and promoting angiogenesis to supply oxygen and nutrients during bone remodeling. (Cao et al., 2023, Hao et al., 2023, Lu et al., 2017)
Polysaccharides contain reactive sites such as hydroxyl, carboxyl, sulfate, and amino groups which enable retention of water molecules or can be modified for drug or growth factor delivery. As a result, polysaccharides are often used to create hydrogels or putties that encapsulate drugs or growth factors or are chemically modified to bind such agents. In either scenario, the natural breakdown of polysaccharide chains enables a slow, more controlled release of drug or growth factor cargo, helping to ensure that healing bone receives a steady supply over time. (Yang et al., 2015).
The Role of Polysaccharides in Reducing Inflammation
Inflammation is a natural part of the bone healing process, but excessive inflammation can be detrimental. Some polysaccharides, such as chitosan, have anti-inflammatory properties that can help reduce excessive inflammation and create a more favorable environment for bone regeneration. By modulating the immune response, chitosan-based materials and other polysaccharide biomaterials help strike the right balance between inflammation and healing.
The Future of Polysaccharide-based Bone Regeneration
The use of polysaccharides in bone repair is still an active area of research, but early results are incredibly promising. The ability to craft scaffolds that mimic natural bone, deliver drugs in a controlled fashion, and modulate inflammation is transforming how we approach bone regeneration. Osteo-P® BGS is a polysaccharide-based biomaterial for tissue engineering, developed by Molecular Matrix, Inc., with promising results for bone repair. (Koleva et al., 2019)
Osteo-P® BGS is an off-the-shelf polysaccharide-based implant tailored for individual patients, providing personalized solutions for bone defects. Moreover, as our understanding of the role of polysaccharides in cell signaling grows, we may discover even more ways these versatile molecules can be used to enhance the body’s natural ability to repair itself. (Lee et al., 2018)
Conclusion
Polysaccharides are proving to be powerful allies in the quest to create the perfect microenvironment for bone repair. By providing biocompatible scaffolds, enabling controlled drug delivery, and helping to manage inflammation, these natural carbohydrates are setting the stage for new and improved approaches to bone healing.
With their unique combination of bioactivity, biocompatibility, and versatility, polysaccharides provide a unique biomaterial to support and enhance the body’s natural bone regeneration processes. The future of bone repair is sweet—and it’s all thanks to these incredible sugar molecules.
References
Cao H, Shi K, Long J, Liu Y, Li L, Ye T, Huang C, Lai Y, Bai X, Qin L, Wang X. PDGF-BB prevents destructive repair and promotes reparative osteogenesis of steroid-associated osteonecrosis of the femoral head in rabbits. Bone. 2023 Feb;167:116645. doi: 10.1016/j.bone.2022.116645. Epub 2022 Dec 17. PMID: 36539110.
Hao, S., Wang, M., Yin, Z., Jing, Y., Bai, L., & Su, J. (2023). Microenvironment-targeted strategy steers advanced bone regeneration. Materials Today Bio, 22, 100741. https://doi.org/10.1016/j.mtbio.2023.100741
Jin, M., Shi, J., Zhu, W., Yao, H., & Wang, D.-A. (2021). Polysaccharide-Based Biomaterials in Tissue Engineering: A Review. Tissue Engineering Part B: Reviews, 27(6), 604–626. https://doi.org/10.1089/ten.teb.2020.0208
Koleva PM, Keefer JH, Ayala AM, Lorenzo I, Han CE, Pham K, Ralston SE, Kim KD, Lee CC. Hyper-Crosslinked Carbohydrate Polymer for Repair of Critical-Sized Bone Defects. Biores Open Access. 2019 Jul 1;8(1):111-120. doi: 10.1089/biores.2019.0021. PMID: 31346493; PMCID: PMC6657362.
Lee, C. C., Hirasawa, N., Garcia, K. G., Ramanathan, D., & Kim, K. D. (2019). Stem and Progenitor Cell Microenvironment for Bone Regeneration and Repair. Regenerative Medicine, 14(7), 693–702. https://doi.org/10.2217/rme-2018-0044
Lu, Z., Kleine-Nulend, J., & Li, B. (2017). Bone Microenvironment, Stem Cells, and Bone Tissue Regeneration. Stem Cells International, 2017, 1–2. https://doi.org/10.1155/2017/1315243
Yang, J., Han, S., Zheng, H., Dong, H., & Liu, J. (2015). Preparation and application of mico/nanoparticles based on natural polysaccharides. Carbohydrate Polymers, 123, 53-66. https://doi.org/10.1016/j.carbpol.2015.01.029
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