Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration

Shazia Shaikh; Shreya Mehrotra; Bas van Bochove; Arun Kumar Teotia; Prerna Singh; Isabella Laurén; Nina C. Lindfors; Jukka Seppälä; Ashok Kumar

doi:10.1021/acsami.4c16195

Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration

Shazia Shaikh, Shreya Mehrotra, Bas van Bochove, Arun Kumar Teotia, Prerna Singh, Isabella Laurén, Nina C. Lindfors, Jukka Seppälä^*, Ashok Kumar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

2 Citations (Scopus)

Abstract

Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young’s modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

Original language	English
Pages (from-to)	65378–65393
Journal	ACS Applied Materials and Interfaces
Volume	16
Issue number	47
DOIs	https://doi.org/10.1021/acsami.4c16195
Publication status	Published - 27 Nov 2024
MoE publication type	A1 Journal article-refereed

Funding

The authors acknowledge the funding received from the Ministry of Human Resource Development (MHRD), India and Indian Council of Medical Research (ICMR), India projects (IMPRINT-6714; UAY/MHRD_IITK_006), MHRD, India project (SPARC/2018-2019/P612/S), Science and Engineering Research Board (SERB), India project (IPA/2020/000026)), Department of Science and Technology (DST), Govt. of India project (DST/NM/NT-2018/48), Department of Biotechnology (DBT), Govt. of India project (DBT/IN/SWEDEN/08/AK/2017-18), and Ortho Regenics Private Limited (ORPL). S.S. acknowledges DBT-BioCARe for financial support (DBT/BSBE/2023606). S.M. acknowledges the Department of Science and Technology, Govt of India for the Inspire Faculty fellowship and research grant. P.S. acknowledges financial support from the DBT-RA program in Biotechnology and Life Sciences. S.S. acknowledges Dr. Ashiq Hussain Pandit for helping in the drawing of chemical structures of polymers. The authors also acknowledge the constant assistance of Mr. Vikas Tiwari and Mr. Mamta Kanujia in this work. Furthermore, A.K.T. and J.S. acknowledge the funding of the Academy of Finland, No. 327248 (ValueBiomat) and No. 327865 (Bioeconomy) and Aalto-India Go-global funding. This work made use of Aalto University Bioeconomy Facilities.

Keywords

3D-printing
bioactive molecules
bone regeneration
digital light processing
poly(trimethylene carbonate)
strontium substituted nanohydroxyapatite

Access to Document

10.1021/acsami.4c16195

https://research.utwente.nl/en/publications/strontium-substituted-nanohydroxyapatite-containing-biodegradable

Cite this

@article{4c8e78f4265e4ac28bcaef4df0833ec8,

title = "Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration",

abstract = "Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9\%, 72.9 ± 0.5\%, and 74.3 ± 1.6\% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95\%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt \%, respectively, in the PTMC matrix. The tensile Young{\textquoteright}s modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.",

keywords = "3D-printing, bioactive molecules, bone regeneration, digital light processing, poly(trimethylene carbonate), strontium substituted nanohydroxyapatite",

author = "Shazia Shaikh and Shreya Mehrotra and \{van Bochove\}, Bas and Teotia, \{Arun Kumar\} and Prerna Singh and Isabella Laur{\'e}n and Lindfors, \{Nina C.\} and Jukka Sepp{\"a}l{\"a} and Ashok Kumar",

note = "Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",

year = "2024",

month = nov,

day = "27",

doi = "10.1021/acsami.4c16195",

language = "English",

volume = "16",

pages = "65378–65393",

journal = "ACS Applied Materials and Interfaces",

issn = "1944-8244",

publisher = "American Chemical Society",

number = "47",

}

TY - JOUR

T1 - Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration

AU - Shaikh, Shazia

AU - Mehrotra, Shreya

AU - van Bochove, Bas

AU - Teotia, Arun Kumar

AU - Singh, Prerna

AU - Laurén, Isabella

AU - Lindfors, Nina C.

AU - Seppälä, Jukka

AU - Kumar, Ashok

PY - 2024/11/27

Y1 - 2024/11/27

N2 - Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young’s modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

AB - Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young’s modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

KW - 3D-printing

KW - bioactive molecules

KW - bone regeneration

KW - digital light processing

KW - poly(trimethylene carbonate)

KW - strontium substituted nanohydroxyapatite

UR - https://www.scopus.com/pages/publications/85209762804

U2 - 10.1021/acsami.4c16195

DO - 10.1021/acsami.4c16195

M3 - Article

AN - SCOPUS:85209762804

SN - 1944-8244

VL - 16

SP - 65378

EP - 65393

JO - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

IS - 47

ER -

Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

BIOECONOMY: BIOECONOMY Alliance for excellence in sustainable biomass refining

VALUEBIOMAT: Bio-oils based polymeric composites; value chain from syntheisis to additive manufacturing

Bioeconomy Research Infrastructure

Cite this

Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Projects

BIOECONOMY: BIOECONOMY Alliance for excellence in sustainable biomass refining

VALUEBIOMAT: Bio-oils based polymeric composites; value chain from syntheisis to additive manufacturing

Equipment

Bioeconomy Research Infrastructure

Cite this