Teriparatide therapy and beta-tricalcium phosphate enhance scaffold reconstruction of mouse femoral defects.
To investigate the efficacy of endocrine parathyroid hormone treatment on tissue-engineered bone regeneration, massive femoral defects in C57Bl/6 mice were reconstructed with either 100:0 or 85:15 poly-lactic acid (PLA)/beta-tricalcium phosphate (β-TCP) scaffolds (hereafter PLA or PLA/βTCP, respectively), which were fabricated with low porosity (<30%) to improve their structural rigidity. Experimental mice were treated starting at 1 week postop with daily subcutaneous injections of 40 μg/kg teriparatide until sacrifice at 9 weeks, whereas control mice underwent the same procedure but were injected with sterile saline. Bone regeneration was assessed longitudinally using planar X-ray and quantitative microcomputed tomography, and the reconstructed femurs were evaluated at 9 weeks either histologically or biomechanically to determine their torsional strength and rigidity. Teriparatide treatment increased bone volume and bone mineral content significantly at 6 weeks and led to enhanced trabeculated bone callus formation that appeared to surround and integrate with the scaffold, thereby establishing union by bridging bone regeneration across the segmental defect in 30% of the reconstructed femurs, regardless of the scaffold type. However, the bone volume and mineral content in the PLA reconstructed femurs treated with teriparatide was reduced at 9 weeks to control levels, but remained significantly increased in the PLA/βTCP scaffolds. Further, bridged teriparatide-treated femurs demonstrated a prototypical brittle bone torsion behavior, and were significantly stronger and stiffer than control specimens or treated specimens that failed to form bridging bone union. Taken together, these observations suggest that intermittent, systemic parathyroid hormone treatment can enhance bone regeneration in scaffold-reconstructed femoral defects, which can be further enhanced by mineralized (βTCP) particles within the scaffold.
Jacobson
Justin A
JA
The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
Yanoso-Scholl
Laura
L
Reynolds
David G
DG
Dadali
Tulin
T
Bradica
Gino
G
Bukata
Susan
S
Puzas
Edward J
EJ
Zuscik
Michael J
MJ
Rosier
Randy
R
O'Keefe
Regis J
RJ
Schwarz
Edward M
EM
Awad
Hani A
HA
D000818:Animals; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005264:Femoral Fractures / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D019379:Teriparatide / Q000008:administration & dosage*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D018786:Bone Substitutes; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D019379:Teriparatide
Bone. 2008 Apr;42(4):806-18
18234576
Bone. 2005 Jun;36(6):959-70
15878317
J Biomed Mater Res A. 2010 Dec 1;95(3):717-26
20725979
J Bone Miner Res. 2007 Dec;22(12):1903-12
17680724
J Orthop Res. 2004 Nov;22(6):1254-60
15475206
Bone. 2010 Feb;46(2):259-66
19766748
J Exp Med. 2004 Mar 15;199(6):805-14
15024046
J Bone Miner Res. 1999 Jun;14(6):960-8
10352105
Bone. 2005 Apr;36(4):678-87
15781006
J Cell Biochem. 1994 Nov;56(3):283-94
7876320
Mol Ther. 2000 Oct;2(4):368-73
11020352
Spine (Phila Pa 1976). 2007 Dec 15;32(26):2996-3006
18091493
Spine J. 2007 Mar-Apr;7(2):235-9
17321975
Spine J. 2008 Nov-Dec;8(6):1011-8
18037352
Spine (Phila Pa 1976). 2008 Aug 15;33(18):E653-5
18708918
N Engl J Med. 2007 Aug 30;357(9):905-16
17761594
J Control Release. 2009 Mar 4;134(2):111-7
19100794
J Biomech. 2007;40(14):3178-86
17524409
Adv Drug Deliv Rev. 2006 Jul 7;58(4):555-76
16790291
J Bone Joint Surg Am. 2005 Apr;87(4):731-41
15805200
Cleve Clin J Med. 2003 Jul;70(7):585-6, 589-90, 592-4 passim
12882381
J Bone Miner Res. 2002 Nov;17(11):2038-47
12412812
J Am Acad Orthop Surg. 2006;14(10 Spec No.):S145-51
17003188
Biomaterials. 2000 Dec;21(24):2529-43
11071603
Spine (Phila Pa 1976). 2008 Jun 15;33(14):1509-16; discussion 1517
18520636
J Bone Joint Surg Br. 2001 Apr;83(3):437-40
11341434
Endocrinology. 2005 Nov;146(11):4577-83
16081646
J Biomed Mater Res A. 2006 Jun 15;77(4):700-6
16550532
J Orthop Res. 2001 Sep;19(5):927-34
11562143
Clin Orthop Relat Res. 2003 Nov;(416):291-302
14646773
J Bone Miner Res. 2003 Dec;18(12):2116-25
14672346
Bone. 2005 Nov;37(5):711-9
16143574
J Am Soc Nephrol. 2000 Jun;11(6):1085-1092
10820172
Int Orthop. 2007 Dec;31(6):735-41
17962946
J Clin Neurosci. 2009 Nov;16(11):1417-20
19665382
Biotechnol Bioeng. 2008 Jan 1;99(1):223-34
17570710
Endocrinology. 2000 May;141(5):1667-74
10803575
Calcif Tissue Int. 2004 Apr;74(4):351-6
15255072
J Bone Miner Res. 1996 Apr;11(4):440-5
8992874
Nat Med. 1999 Jul;5(7):753-9
10395319
Curr Gene Ther. 2004 Sep;4(3):263-76
15384940
Bone. 2007 Jun;40(6):1475-82
17369013
J Biomed Mater Res A. 2003 Nov 1;67(2):591-8
14566802
J Invest Dermatol. 2006 Sep;126(9):2127-34
16675960
Biochem Biophys Res Commun. 2010 Apr 2;394(2):323-9
20206607
South Med J. 2005 Nov;98(11):1114-7
16353381
J Cell Biochem. 2008 Sep 1;105(1):219-26
18494002