Utilizing Supercritical Carbon dioxide in Biologically Extracted Chitin Hydrogels to Scaffold Human Osteoblasts

Zacualpan Ellenberg^*
*Correspondence: Zacualpan Ellenberg, Department of Biodiversity, Montpellier University, Montpellier SupAgro, Montpellier, France, Email:

Keywords

Supercritical carbon dioxide • Chitin hydrogels • Osteoblasts • Tissue engineering • Bone regeneration

Introduction

In the realm of tissue engineering and regenerative medicine, the quest for biomaterials that can effectively mimic the Extracellular Matrix (ECM) and support cell growth is paramount. Chitin, a polysaccharide abundant in crustacean shells, has garnered attention due to its biocompatibility and structural similarities to ECM components. When extracted and processed into hydrogels, chitin offers a versatile scaffold for various cell types, including osteoblasts crucial for bone regeneration. Recent advancements in material science have leveraged supercritical carbon dioxide (scCO₂) as a solvent to fabricate chitin hydrogels. This method stands out for its ability to produce materials under mild conditions, preserving the structural integrity and bioactivity of chitin while maintaining an environmentally sustainable approach. Unlike conventional solvents, scCO₂ offers a solvent-free product, ensuring minimal residual toxicity and enhancing the overall biocompatibility of the resulting hydrogel. The application of scCO₂ in chitin hydrogel formation involves a process where chitin is dissolved in scCO₂ under specific pressure and temperature conditions, followed by rapid depressurization to form a porous structure akin to natural ECM. This porous network not only facilitates nutrient diffusion but also provides a three-dimensional environment conducive to cell adhesion, proliferation and differentiation—essential factors for osteoblasts tasked with bone formation [1].

Osteoblasts, the bone-forming cells of the body, thrive in environments that mimic the natural bone matrix. Chitin hydrogels scaffolded with scCO₂ have demonstrated significant promise in fostering osteoblast growth and differentiation. Studies have shown that these hydrogels promote osteogenic markers and enhance mineralization, indicating their potential application in bone tissue engineering. The porous nature of scCO₂-treated chitin hydrogels supports vascular ingrowth and the deposition of mineralized tissue, crucial for effective bone regeneration. Furthermore, the use of scCO₂ aligns with current trends in green chemistry and sustainable manufacturing practices. Its non-toxic, non-flammable and readily available properties make it an ideal solvent for biomedical applications, reducing environmental impact compared to traditional organic solvents

Literature Review

the integration of supercritical carbon dioxide in biologically extracted chitin hydrogels represents a significant advancement in biomaterials for osteoblast scaffolding. The combination of chitin's biocompatibility with scCO2'_s green processing capabilities offers a synergistic platform for developing next-generation biomaterials. Looking forward, continued research aims to optimize these hydrogels for clinical applications, addressing challenges such as scalability and long-term stability. Ultimately, scCO₂-treated chitin hydrogels hold promise as a cornerstone in the field of orthopedic regenerative medicine, paving the way for enhanced bone repair strategies and improved patient outcomes.

Supercritical carbon dioxide (scCO₂) is increasingly utilized in the fabrication of chitin hydrogels derived from biological sources, particularly crustacean shells. These hydrogels serve as scaffolds for human osteoblasts, pivotal in bone tissue engineering due to chitin's biocompatibility and scCO₂'s eco-friendly processing characteristics. This article explores the application of scCO₂ in creating chitin hydrogels, emphasizing their potential in promoting osteoblast proliferation, differentiation and mineralization. The review discusses scCO₂'s advantages, including its mild processing conditions and ability to maintain biomolecule integrity, underscoring the promising role of scCO₂-treated chitin hydrogels in advancing orthopedic regenerative therapies.

Mild Processing Conditions: scCO₂ operates under relatively low temperatures and pressures, minimizing thermal and oxidative degradation of biomolecules such as chitin. This gentle processing helps preserve the native structure and bioactivity of chitin, crucial for maintaining its effectiveness as a scaffold for osteoblasts. Unlike traditional organic solvents, scCO₂ is a clean, green solvent that leaves behind no residues in the final product. This characteristic ensures minimal cytotoxicity and supports the biocompatibility of chitin hydrogels, making them suitable for biomedical applications. The use of scCO₂ enables the creation of porous chitin hydrogels with interconnected networks resembling natural ECM. These pores facilitate nutrient exchange, waste removal and cell migration—key processes for supporting osteoblast viability and function in bone regeneration. As the field of biomaterials increasingly emphasizes sustainable practices, scCO₂ stands out for its eco-friendly profile. It is non-toxic, non-flammable and readily recyclable, aligning with global efforts to reduce environmental impact in manufacturing processes [2].

Chitin hydrogels scaffolded with scCO₂ have been shown to enhance the expression of osteogenic markers such as osteocalcin, Runx2 and alkaline phosphatase in osteoblasts. These markers indicate the cells' commitment to bone-forming pathways, essential for effective bone regeneration. The porous structure of scCO₂-treated chitin hydrogels supports the deposition of mineralized tissue, mimicking the natural process of bone formation. This feature is critical for developing biomaterials that can integrate seamlessly with existing bone tissue and promote long-term structural integrity. Preclinical studies utilizing animal models have demonstrated the efficacy of scCO₂-treated chitin hydrogels in promoting bone healing and regeneration. These studies validate the hydrogel's biocompatibility, safety and ability to support new bone formation in vivo, laying the groundwork for future clinical trials. While still in the research phase, there is optimism regarding the clinical translation of scCO₂-treated chitin hydrogels. Challenges such as scalability, cost-effectiveness and regulatory approvals remain, but ongoing advancements in biomaterial engineering and manufacturing technologies are addressing these hurdles [3].

Moving forward, research efforts are focused on optimizing scCO₂ processing parameters to further enhance the mechanical properties, biodegradability and bioactivity of chitin hydrogels. Additionally, integrating bioactive molecules, growth factors, or nanomaterials into scCO₂-treated chitin hydrogels could impart additional functionalities, such as antimicrobial properties or enhanced cell signaling capabilities. Moreover, interdisciplinary collaborations between material scientists, bioengineers and clinicians are crucial for bridging the gap between benchtop innovations and clinical applications. Long-term studies evaluating the durability and efficacy of scCO₂-treated chitin hydrogels in large animal models and clinical trials will provide critical data on safety and therapeutic efficacy. The utilization of supercritical carbon dioxide in biologically extracted chitin hydrogels represents a promising strategy for scaffolding human osteoblasts in bone tissue engineering. This approach leverages the natural biocompatibility of chitin with the sustainable processing capabilities of scCO₂, paving the way for advanced biomaterials that could revolutionize orthopedic regenerative medicine. As research progresses, scCO₂-treated chitin hydrogels hold immense potential to address current clinical challenges in bone repair and contribute to improved patient outcomes worldwide [4].

Discussion

Despite the promising advancements, several challenges and considerations remain in the development and application of scCO₂-treated chitin hydrogels for osteoblast scaffolding. Enhancing the mechanical strength and stability of chitin hydrogels remains a critical goal. While scCO₂ processing can create porous structures conducive to cell growth, optimizing these properties to withstand physiological loads in vivo is essential for long-term success. Achieving controlled biodegradability is crucial to ensure that chitin hydrogels degrade at a rate matching new tissue formation. Balancing degradation kinetics with scaffold integrity is essential for maintaining structural support during the critical phases of bone healing. Scaling up production of scCO₂-treated chitin hydrogels to meet clinical demands while ensuring cost-effectiveness is a significant challenge. Process optimization and innovative manufacturing techniques are necessary to reduce production costs and facilitate widespread clinical adoption. Meeting regulatory standards for biomaterials intended for clinical use is a complex process. Comprehensive preclinical studies, including biocompatibility testing, safety assessments and efficacy evaluations, are necessary to obtain regulatory approvals from health authorities.

Incorporating bioactive molecules, such as growth factors or peptides, into scCO₂-treated chitin hydrogels could enhance their biological activity and therapeutic potential. These modifications can promote specific cell behaviors, such as enhanced osteogenic differentiation or angiogenesis, further supporting bone regeneration. Developing multifunctional chitin hydrogels that combine mechanical support with antimicrobial properties or drug delivery capabilities represents a promising avenue for future research. These innovations could address common complications in orthopedic surgeries, such as infection and inflammation. Tailoring chitin hydrogels to individual patient needs through advanced imaging and 3D printing technologies offers opportunities for personalized orthopedic treatments. Customized scaffolds could optimize bone repair outcomes by matching patient-specific anatomical and biomechanical requirements. Exploring synergistic approaches by combining scCO₂-treated chitin hydrogels with other biomaterials, such as ceramics or synthetic polymers, could leverage complementary properties to enhance scaffold performance. These hybrid materials could provide superior mechanical strength, enhanced bioactivity and improved integration with host tissue [5,6].

Conclusion

The integration of supercritical carbon dioxide in biologically extracted chitin hydrogels represents a significant advancement in orthopedic regenerative medicine. By harnessing the natural biocompatibility of chitin and the eco-friendly processing capabilities of scCO₂, researchers are paving the way for innovative biomaterials that can scaffold human osteoblasts and promote bone regeneration. While challenges such as mechanical strength, scalability and regulatory approval remain, ongoing research and technological advancements offer promising solutions. Future studies focusing on biofunctionalization, personalized medicine and combination therapies hold the potential to further enhance the efficacy and clinical translation of scCO2-treated chitin hydrogels. Ultimately, these efforts aim to improve patient outcomes and address unmet clinical needs in bone repair and regeneration worldwide.

Acknowledgement

None.

Conflict of Interest

None.

References

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