Development of a growth factor bioavailability enhanced allograft (GFBA) for bone regeneration

Area of Science:

• Biomaterials Science
• Orthopedic Surgery
• Regenerative Medicine

Background:

• Bone morphogenetic proteins (BMPs) are crucial for osteoinduction and bone regeneration.
• Human demineralized bone matrix (DBM) is a common bone graft substitute but has limited osteoinductive potential due to processing limitations.
• Enhancing the bioavailability of native BMPs in allografts is key to improving bone regeneration efficacy.

Purpose of the Study:

• To introduce a novel processing method, Natural Matrix Protein (NMP), designed to enhance allograft bioactivity by increasing native BMP bioavailability.
• To quantify BMP-7 release from NMP and DBM.
• To evaluate the osteoinductive potential of NMP in vitro and in vivo.

Main Methods:

• BMP-7 release was quantified from NMP and DBM (bovine and human) using acidic and physiologic extracts.
• Sustained release of BMP-7 and total protein was assessed over 12 weeks in simulated body fluid.
• In vitro osteoinductive potential was evaluated using C2C12 cells (alkaline phosphatase activity).
• In vivo osteoinductivity was assessed in athymic rats, comparing human NMP to human DBM and Infuse Bone Graft using histology and microCT.

Main Results:

• NMP significantly increased BMP-7 levels compared to DBM in both bovine and human bone.
• NMP demonstrated sustained release of BMP-7 and total protein for up to 12 weeks.
• NMP induced a greater than tenfold increase in alkaline phosphatase activity in vitro.
• Human NMP showed enhanced osteoinductivity in vivo, with significantly more mineralized bone and higher bone volume fraction compared to DBM and Infuse Bone Graft.

Conclusions:

• The novel NMP process effectively increases BMP-7 bioavailability and enhances allograft osteoinductivity.
• NMP implants facilitate sustained release of BMP and total protein.
• NMP demonstrates significant potential for improving bone regeneration applications.