Parathyroid hormone gene-activated matrix with DFDBA/collagen composite matrix enhances bone regeneration in rat calvarial bone defects

Lee, Po Hui; Yew, Tu Lai; Lai, Yung‐Lien; Lee, Shyh Yuan; Chen, Hen Li

doi:10.1016/j.jcma.2017.12.004

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…Local delivery of PTH treatment has also been achieved through use of gene‐activated matrices (GAM) which induce local production of PTH at the defect site. Treatment with PTH‐GAM and a collagen matrix has been shown to promote bone regeneration in a craniomaxillofacial bone defect . Though pulsatile release of PTH from biomaterial scaffolds has been explored, they have not been tested extensively in vivo for bone regeneration applications .…”

Section: Effect Of Locally Delivered Pth On Fracture Healing and Bonementioning

confidence: 99%

Parathyroid hormone for bone regeneration

Wojda

Donahue

2018

Journal Orthopaedic Research

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Delayed healing and/or non-union occur in approximately 5-10% of the fractures that occur annually in the United States. Segmental bone loss increases the probability of non-union. Though grafting can be an effective treatment for segmental bone loss, autografting is limited for large defects since a limited amount of bone is available for harvest. Parathyroid hormone (PTH) is a key regulator of calcium homeostasis in the body and plays an important role in bone metabolism. Presently PTH is FDA approved for use as an anabolic treatment for osteoporosis. The anabolic effect PTH has on bone has led to research on its use for bone regeneration applications. Numerous studies in animal models have indicated enhanced fracture healing as a result of once daily injections of PTH. Similarly, in a human case study, non-union persisted despite treatment attempts with internal fixation, external fixation, and autograft in combination with BMP-7, until off label use of PTH1-84 was utilized. Use of a biomaterial scaffold to locally deliver PTH to a defect site has also been shown to improve bone formation and healing around dental implants in dogs and drill defects in sheep. Thus, PTH may be used to promote bone regeneration and provide an alternative to autograft and BMP for the treatment of large segmental defects and non-unions. This review briefly summarizes the unmet clinical need for improved bone regeneration techniques and how PTH may help fill that void by both systemically and locally delivered PTH for bone regeneration applications. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2586-2594, 2018.

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Section: Effect Of Locally Delivered Pth On Fracture Healing and Bonementioning

confidence: 99%

Parathyroid hormone for bone regeneration

Wojda

Donahue

2018

Journal Orthopaedic Research

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“…24 Use of gene-activated matrices to induce local production of PTH have also been used in conjunction with a collagen matrix to promote bone regeneration in a craniomaxillofacial bone defect. 25 These studies indicate that PTH delivered locally via degradable scaffolds may be an alternative to bone grafts for the treatment of open fractures or critical size bone defects. Local PTH delivery has several advantages over systemic PTH delivery for the repair of bone defects.…”

mentioning

confidence: 94%

“… A combination of local delivery of PTH via a gene‐activated matrix and systemic (40 µg/kg/day) has also been shown to provide improved healing of a critical size osteotomy in rats. Use of gene‐activated matrices to induce local production of PTH have also been used in conjunction with a collagen matrix to promote bone regeneration in a craniomaxillofacial bone defect . These studies indicate that PTH delivered locally via degradable scaffolds may be an alternative to bone grafts for the treatment of open fractures or critical size bone defects.…”

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confidence: 99%

Thiol‐ene Hydrogels for Local Delivery of PTH for Bone Regeneration in Critical Size defects

Wojda

Marozas

Anseth

et al. 2019

Journal Orthopaedic Research

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Neither allograft nor commercially available bone graft substitutes provide the same quality of bone healing as autograft. Incorporation of bioactive molecules like parathyroid hormone (PTH) within bone graft substitute materials may provide similar, if not better treatment options to grafting. The goal of this work was to develop a biomaterial system for the local delivery of PTH to large bone defects for promoting bone regeneration. PTH was loaded in a thiol‐ene hydrogel at several concentrations and polymerized in and around an osteoconductive poly(propylene fumarate) (PPF) scaffold. PTH was shown to be bioactive when released from the hydrogel for up to 21 days. Eighty percent of the PTH was released by day 3 with the remaining 20% released by day 14. Bone healing was quantified in rat critical size femoral defects that were treated with hydrogel/PPF and 0, 1, 3, 10, or 30 µg of PTH. Although complete osseous healing was not observed in all samples in any one treatment group, all samples in the 10 µg PTH group were bridged fully by bone or a combination of bone and cartilage containing hypertrophic chondrocytes and endochondral ossification. Outcome measures indicated improved defect bridging by a combination of bony and cartilaginous tissue in the 10 μg treatment group compared with empty bone defects and defects treated with only hydrogel/PPF (i.e., without PTH). Given the tailorability of the hydrogel, future studies will investigate the effects of prolonged gradual PTH release on bone healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:536–544, 2020

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Insights into the use of genetically modified decellularized biomaterials for tissue engineering and regenerative medicine

Zhu

Jiang

et al. 2022

Advanced Drug Delivery Reviews

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Parathyroid hormone gene-activated matrix with DFDBA/collagen composite matrix enhances bone regeneration in rat calvarial bone defects

Cited by 4 publications

References 43 publications

Parathyroid hormone for bone regeneration

Parathyroid hormone for bone regeneration

Thiol‐ene Hydrogels for Local Delivery of PTH for Bone Regeneration in Critical Size defects

Insights into the use of genetically modified decellularized biomaterials for tissue engineering and regenerative medicine

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