Bionic silicified collagen scaffold

Summary

Abstract

Bionic silicified collagen scaffold is a new kind of bionic silicified material shows good porosity, tensile property and silicic acid release effect. By promoting peripheral sensory nerve growth and neuropeptide secretion, it can promote bone regeneration, which has the functions of innervation, osteogenic coupling and tissue mineralization. [1][2] It solves the problem that most biomaterials cannot induce sufficient angiogenesis and innervation in complex bone loss, and has great potential in clinical

application of bone regeneration. Keywords: Bionic silicified collagen scaffold；Physical and chemical properties;fucctions；foreground

Introduction

In this study, choline chloride was used as a collagen preconditioning agent and a silicic acid stabilizer to synthesize a new bionic silicification

Materials. This material can be promoted by activating the sensory mTOR signaling pathway and further secreting Sema3A

Bone defect repair. Biomimetic silicified collagen scaffolds can promote innervation and angiogenesis during bone regeneration

It not only provides a new idea for the theory of neuro-bone coupling, but also provides a new strategy for the treatment of bone defects.

Literature Review

Research group from Air Force Military Medical University has proposed the concept of intracollagenous bionic silicification using polyamine-induced liquid-phase silicic acid precursors and constructed a bionic silicified material. [3] By mixing Silbond 40, anhydrous ethanol, deionized water and 37% hydrochloric acid, trimming the three-dimensional recombinant type I collagen sponge into a collagen block and placing in a choline stabilized silicic acid precursor solution for 7 days. The silicified collagen scaffold showed good porosity and the tensile modulus [3] The new material highly improves the efficiency of bone defect repair by promoting the growth of peripheral sensory nerves and osteogenic coupling, which provides an experimental basis for artificial bone materials to regulate bone regeneration. [3][4]

Property: Profile

Porosity: P=86.7%

Tensile strength: 5.96±0.73 MPa

Toxicity: BV/TV<0.5, BMD<0.5, Th.Th<0.5

Silicon content Content of silicon: 30.77±3.54 wt%

Chemical composition and diagram: See Fig 3 (a) for details

References

[1]J.J. Fan, T.W. Mu, J.J. Qin, L. Bi, G.X. Pei Different effects of implanting sensory nerve or blood vessel on the vascularization, neurotization, and osteogenesis of tissue-engineered bone in vivo BioMed Res. Int., 2014 (2014), 10.1155/2014/412570

[2]G. Lalwani, M. D'Agati, B. Farshid, B.Sitharaman Carbon and Inorganic Nanomaterial-Reinforced Polymeric Nanocomposites for Bone Tissue Engineering, Elsevier Ltd (2016), 10.1016/B978-1-78242-452-9.00002-9

[3]Ma, Y.-X. et al. (2022) “Silicified collagen scaffold induces Semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration,” Bioactive Materials, 9, pp. 475–490. [4]K. Dashnyam, J.O. Buitrago, T. Bold, N. Mandakhbayar, R.A. Perez, J.C. Knowles, J.H. Lee, H.W. Kim Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds Biomater. Sci., 7 (2019), pp. 5221-5231, 10.1039/c9bm01103j

[5] Tomlinson RE, Li Z, Zhang Q, Goh BC, Li Z, Thorek DLJ, Rajbhandari L, Brushart TM, Minichiello L, Zhou F, Venkatesan A, Clemens TL. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone[J]. Cell Rep. 2016 Sep 6;16(10):2723-35

[6] Xie M, Kamenev D, Kaucka M, Kastriti ME, Zhou B, Artemov AV, Storer M, Fried K, Adameyko I, Dyachuk V, Chagin AS. Schwann cell precursors contribute to skeletal formation during embryonic development in mice and zebrafish[J]. Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):15068-73.

[7] Heffner MA, Anderson MJ, Yeh GC, Genetos DC, Christiansen BA. Altered bone development in a mouse model of peripheral sensory nerve inactivation[J]. J Musculoskelet Neuronal Interact. 2014 Mar;14(1):1-9

Literature Review

Artificial bone repair materials have been widely used in clinical practice, but they cannot fully mimic the biological properties of autogenous bone.[1] The development of highly bionic and osteogenic bone repair materials has been a hot topic in the field of biomaterials and medicine.[2] Among the various ways to construct bionic artificial bone repair materials, the use of sensory nerves to regulate bone regeneration is considered a promising approach. The group has proposed the concept of intracollagenous bionic silicification using polyamine-induced liquid phase silica precursors for the first time in the world, and constructed a bionic silicified adhesive material with intrafibrillar mineralisation properties, and demonstrated good bone-enhancing effects. [3]

The specific procedure is as follows: mix Silbond 40, anhydrous ethanol, deionised water and 37% hydrochloric acid in a molar ratio of 1.875:396.79:12.03:0.0218 (mass 15:182.8:2.167:0.008) at room temperature. The above 3 % orthosilicic acid solution is mixed with a magnetic stirrer for 1 hour, then mixed with 36 mM choline chloride and other volumes, and the pH of the final solution is adjusted to 5,5. After mixing and dilution, the concentration of orthosilicic acid in the choline chloride-stabilised silicic acid precursor solution is 1.5% and it is stored for use. The three-dimensional recombinant type I collagen sponge (ACE collagen) was cut into a collagen block with a diameter of 0.4 cm and washed three times with deionised water for use. ACE collagen was soaked in 36 mM choline and mixed in a magnetic stirrer for 4 hours, then placed in a choline-stabilised silica precursor solution for 7 days. The final silicified collagen scaffold was spongy and showed good compressibility after drying[3].

In this study, a biomimetic silicified collagen scaffold construction method using choline chloride as both collagen pretreatment agent and silicic acid stabiliser was developed. The new biomimetic silicified material can significantly improve the efficiency of bone defect repair by promoting the growth of peripheral sensory nerves and the secretion of neuropeptides, which provides an experimental basis for artificial bone materials to use sensory nerves to regulate bone regeneration. Silicon-containing materials can promote the secretion of Sema3A by activating the mTOR signalling pathway of the peripheral sensory nerve and then induce bone regeneration. This mechanism opens up a new perspective for the study of neuro-bone coupling theory.[3][4]

References

[1]J.J. Fan, T.W. Mu, J.J. Qin, L. Bi, G.X. Pei

Different effects of implanting sensory nerve or blood vessel on the vascularization, neurotization, and osteogenesis of tissue-engineered bone in vivo

BioMed Res. Int., 2014 (2014), 10.1155/2014/412570

[2]G. Lalwani, M. D'Agati, B. Farshid, B.Sitharaman

Carbon and Inorganic Nanomaterial-Reinforced Polymeric Nanocomposites for Bone Tissue Engineering, Elsevier Ltd (2016), 10.1016/B978-1-78242-452-9.00002-9

[3]Ma, Y.-X. et al. (2022) “Silicified collagen scaffold induces Semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration,” Bioactive Materials, 9, pp. 475–490.

[4]K. Dashnyam, J.O. Buitrago, T. Bold, N. Mandakhbayar, R.A. Perez, J.C. Knowles, J.H. Lee, H.W. Kim

Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds Biomater. Sci., 7 (2019), pp. 5221-5231, 10.1039/c9bm01103j

Application

The application of this material in the experiment of distal femoral defects in rats shows that it can significantly promote the formation of new bones, accompanied by extensive nerve innervation and angiogenesis.

Promote osteogenic coupling: In vivo and in vitro, it can significantly improve the coupling of neonatal bone tissue.

Helps form innervation of sensory nerve: Activate the mTOR signaling pathway of sensory nerves and control the subtle balance between sensory neurons and vascular formation

Promote tissue mineralization: The material improves the speed of Mineralized bone tissue formation, bone volume fraction, bone density.

Biomimetic mineralized collagen scaffolds enhancing odontogenic differentiation of hDPSCs and dentin regeneration through modulating mechanical microenvironment.

Artificial skin is a synthetic material that mimics the structure and function of human skin, usually made from polymers or biological materials (siliconized collagen). It can be used to replace or repair defective skin caused by injury, disease, or congenital disease.

Artificial skin is usually composed of multiple layers of structure, including layers such as epidermis, dermis, and subcutaneous tissue. The epidermis layer is responsible for protecting the inside and regulating moisture, temperature and preventing the entry of harmful substances, the dermis layer provides support and elasticity to the body, forms blood vessels and carries out metabolism and transmits information, and the subcutaneous tissue layer helps maintain body temperature stability, among other things.

Processing route

Silbond 40, anhydrous ethanol, deionised water and 37% hydrochloric acid were mixed at room temperature in the molar ratio of 1.875:396.79:12.03:0.0218 molar ratio (15:182.8:2.167:0.008 by mass). The above The 3% orthosilicicic acid solution was mixed for 1 hour using a magnetic stirrer and then homogenously mixed with 36 mM choline chloride in equal volumes and the final solution pH was adjusted to 5.5. After mixing and dilution, the choline chloride-stabilised silicic acid precursor solution contained a 1.5% concentration of orthosilicicic acid and was stored. ACE collagen was soaked in 36 mM choline and mixed with a magnetic stirrer for 4 hours before being placed in a choline-stabilised silicate precursor solution for 7 days, with the silicate precursor solution being changed daily.