Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation

Jacob M. Miszuk, Tao Xu, Qingqing Yao, Fang Fang, Josh D. Childs, Zhongkui Hong, Jianning Tao, Hao Fong, Hongli Sun

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

Original languageEnglish (US)
Pages (from-to)194-202
Number of pages9
JournalApplied Materials Today
Volume10
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

Polycaprolactone
Scaffolds (biology)
Scaffolds
Bone
Proteins
Durapatite
Hydroxyapatite
Nanofibers
polycaprolactone
Agglomeration
Orthopedics

Keywords

  • 3D electrospun nanofibrous scaffold
  • Bone regeneration
  • Hydroxyapatite functionalization
  • Osteogenic differentiation
  • Phenamil

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation. / Miszuk, Jacob M.; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D.; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli.

In: Applied Materials Today, Vol. 10, 01.03.2018, p. 194-202.

Research output: Contribution to journalArticle

Miszuk, Jacob M. ; Xu, Tao ; Yao, Qingqing ; Fang, Fang ; Childs, Josh D. ; Hong, Zhongkui ; Tao, Jianning ; Fong, Hao ; Sun, Hongli. / Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation. In: Applied Materials Today. 2018 ; Vol. 10. pp. 194-202.
@article{103ea27d6f6c4684a9ab22d039c19033,
title = "Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation",
abstract = "Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.",
keywords = "3D electrospun nanofibrous scaffold, Bone regeneration, Hydroxyapatite functionalization, Osteogenic differentiation, Phenamil",
author = "Miszuk, {Jacob M.} and Tao Xu and Qingqing Yao and Fang Fang and Childs, {Josh D.} and Zhongkui Hong and Jianning Tao and Hao Fong and Hongli Sun",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.apmt.2017.12.004",
language = "English (US)",
volume = "10",
pages = "194--202",
journal = "Applied Materials Today",
issn = "2352-9407",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Functionalization of PCL-3D electrospun nanofibrous scaffolds for improved BMP2-induced bone formation

AU - Miszuk, Jacob M.

AU - Xu, Tao

AU - Yao, Qingqing

AU - Fang, Fang

AU - Childs, Josh D.

AU - Hong, Zhongkui

AU - Tao, Jianning

AU - Fong, Hao

AU - Sun, Hongli

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

AB - Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro, however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed that this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting that PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

KW - 3D electrospun nanofibrous scaffold

KW - Bone regeneration

KW - Hydroxyapatite functionalization

KW - Osteogenic differentiation

KW - Phenamil

UR - http://www.scopus.com/inward/record.url?scp=85039077765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039077765&partnerID=8YFLogxK

U2 - 10.1016/j.apmt.2017.12.004

DO - 10.1016/j.apmt.2017.12.004

M3 - Article

VL - 10

SP - 194

EP - 202

JO - Applied Materials Today

JF - Applied Materials Today

SN - 2352-9407

ER -