title: Teriparatide therapy and beta-tricalcium phosphate enhance scaffold reconstruction of mouse femoral defects.
abstract: 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.
authors.affiliation: The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Jacobson
authors.forename: Laura
authors.initials: L
authors.lastname: Yanoso-Scholl
authors.forename: David G
authors.initials: DG
authors.lastname: Reynolds
authors.forename: Tulin
authors.initials: T
authors.lastname: Dadali
authors.forename: Gino
authors.initials: G
authors.lastname: Bradica
authors.forename: Susan
authors.initials: S
authors.lastname: Bukata
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Puzas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zuscik
authors.forename: Randy
authors.initials: R
authors.lastname: Rosier
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
mesh_terms: 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
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D019379:Teriparatide
references.citation: Bone. 2008 Apr;42(4):806-18
references.pmid: 18234576
references.citation: Bone. 2005 Jun;36(6):959-70
references.pmid: 15878317
references.citation: J Biomed Mater Res A. 2010 Dec 1;95(3):717-26
references.pmid: 20725979
references.citation: J Bone Miner Res. 2007 Dec;22(12):1903-12
references.pmid: 17680724
references.citation: J Orthop Res. 2004 Nov;22(6):1254-60
references.pmid: 15475206
references.citation: Bone. 2010 Feb;46(2):259-66
references.pmid: 19766748
references.citation: J Exp Med. 2004 Mar 15;199(6):805-14
references.pmid: 15024046
references.citation: J Bone Miner Res. 1999 Jun;14(6):960-8
references.pmid: 10352105
references.citation: Bone. 2005 Apr;36(4):678-87
references.pmid: 15781006
references.citation: J Cell Biochem. 1994 Nov;56(3):283-94
references.pmid: 7876320
references.citation: Mol Ther. 2000 Oct;2(4):368-73
references.pmid: 11020352
references.citation: Spine (Phila Pa 1976). 2007 Dec 15;32(26):2996-3006
references.pmid: 18091493
references.citation: Spine J. 2007 Mar-Apr;7(2):235-9
references.pmid: 17321975
references.citation: Spine J. 2008 Nov-Dec;8(6):1011-8
references.pmid: 18037352
references.citation: Spine (Phila Pa 1976). 2008 Aug 15;33(18):E653-5
references.pmid: 18708918
references.citation: N Engl J Med. 2007 Aug 30;357(9):905-16
references.pmid: 17761594
references.citation: J Control Release. 2009 Mar 4;134(2):111-7
references.pmid: 19100794
references.citation: J Biomech. 2007;40(14):3178-86
references.pmid: 17524409
references.citation: Adv Drug Deliv Rev. 2006 Jul 7;58(4):555-76
references.pmid: 16790291
references.citation: J Bone Joint Surg Am. 2005 Apr;87(4):731-41
references.pmid: 15805200
references.citation: Cleve Clin J Med. 2003 Jul;70(7):585-6, 589-90, 592-4 passim
references.pmid: 12882381
references.citation: J Bone Miner Res. 2002 Nov;17(11):2038-47
references.pmid: 12412812
references.citation: J Am Acad Orthop Surg. 2006;14(10 Spec No.):S145-51
references.pmid: 17003188
references.citation: Biomaterials. 2000 Dec;21(24):2529-43
references.pmid: 11071603
references.citation: Spine (Phila Pa 1976). 2008 Jun 15;33(14):1509-16; discussion 1517
references.pmid: 18520636
references.citation: J Bone Joint Surg Br. 2001 Apr;83(3):437-40
references.pmid: 11341434
references.citation: Endocrinology. 2005 Nov;146(11):4577-83
references.pmid: 16081646
references.citation: J Biomed Mater Res A. 2006 Jun 15;77(4):700-6
references.pmid: 16550532
references.citation: J Orthop Res. 2001 Sep;19(5):927-34
references.pmid: 11562143
references.citation: Clin Orthop Relat Res. 2003 Nov;(416):291-302
references.pmid: 14646773
references.citation: J Bone Miner Res. 2003 Dec;18(12):2116-25
references.pmid: 14672346
references.citation: Bone. 2005 Nov;37(5):711-9
references.pmid: 16143574
references.citation: J Am Soc Nephrol. 2000 Jun;11(6):1085-1092
references.pmid: 10820172
references.citation: Int Orthop. 2007 Dec;31(6):735-41
references.pmid: 17962946
references.citation: J Clin Neurosci. 2009 Nov;16(11):1417-20
references.pmid: 19665382
references.citation: Biotechnol Bioeng. 2008 Jan 1;99(1):223-34
references.pmid: 17570710
references.citation: Endocrinology. 2000 May;141(5):1667-74
references.pmid: 10803575
references.citation: Calcif Tissue Int. 2004 Apr;74(4):351-6
references.pmid: 15255072
references.citation: J Bone Miner Res. 1996 Apr;11(4):440-5
references.pmid: 8992874
references.citation: Nat Med. 1999 Jul;5(7):753-9
references.pmid: 10395319
references.citation: Curr Gene Ther. 2004 Sep;4(3):263-76
references.pmid: 15384940
references.citation: Bone. 2007 Jun;40(6):1475-82
references.pmid: 17369013
references.citation: J Biomed Mater Res A. 2003 Nov 1;67(2):591-8
references.pmid: 14566802
references.citation: J Invest Dermatol. 2006 Sep;126(9):2127-34
references.pmid: 16675960
references.citation: Biochem Biophys Res Commun. 2010 Apr 2;394(2):323-9
references.pmid: 20206607
references.citation: South Med J. 2005 Nov;98(11):1114-7
references.pmid: 16353381
references.citation: J Cell Biochem. 2008 Sep 1;105(1):219-26
references.pmid: 18494002