CATEGORIES OF BONE GRAFT
Bone graft selection is critical to the outcome of any bone healing procedure. There are currently over 200 different bone grafts available to surgeons today, each with substantial differences in technology, materials, mechanisms of action, indications, and clinical evidence.
Bone grafts can be categorized based on:
- Mechanism of action (MOA)
- Approved indication
- Performance data
Recombinant proteins are naturally occurring proteins that play an active role in bone formation and maintenance. The human sequence of these proteins can be synthetically manufactured in a consistent, controlled process — commonly referred to as "human recombinant" technology, or recombinant human bone morphogenetic protein (rhBMP).
- Composition: rhBMP
- MOA: Highly osteoinductive and provides a strong signal for bone formation
- Approval: Premarket approval (PMA) or humanitarian device exemption (HDE)
- Data Required: PMAs require a pivotal human clinical trial to show safety and efficacy.
Synthetic Bone Graft
An osteoconductor, synthetic autograft extender bulks up the supply of available autograft bone.
- Composition: Synthetically produced minerals and ceramics
- MOA: Provides an osteoconductive passive scaffold for bone formation
- Approval: 510(k) clearance as a bone void filler for applications not intrinsic to the stability of the bony structure
- Data required: 510(k) clearance typically requires bench testing or preclinical data, usually in rabbit or sheep.
Allograft Bone Graft
There are many different allograft products or forms available for use. Some allograft tissue functions through osteoconduction and mild osteoinduction when demineralized, and include mineralized tissue, demineralized tissue, and allograft tissue plus cells.
These products are also regulated differently based on how they are processed. For example, tissue based products that have a 351 HCT/Ps designation are regulated like a medical device and require a submission to the FDA for clearance. Tissue based products that fall into the minimally manipulated category are regulated as a 361 HCT/P and do not require a submission to the FDA.
- Composition: Donor bone and tissue
- Demineralized MOA: osteoconductive and osteoinductive.
- 351 Approval: Formulated allograft products such as DBMs have 510(k) clearance as a bone void filler for applications not intrinsic to the stability of the bony structure.
- Data required: 510(k) clearance typically requires bench testing or preclinical data, usually in a rabbit or sheep and must perform substantially equivalent to an existing product on the market.
- Composition: Donor bone and tissue
- Mineralized tissue MOA: osteoconductive
- Minimally manipulated Demineralized tissue MOA: osteoconductive & Osteoinductive
- 361 Approval. Minimally manipulated Human cellular and tissue products that meet FDA criteria for regulation solely under 21 CFR Part 1271 regulations for 361 HCT/Ps are not regulated as medical devices, and as such do not require 510(k) clearance.
- Data required: 361 HCT/Ps require no data filing with the FDA.
Xenograft is bone taken from an animal source and transplanted into the body. It is treated at high temperatures (600 C to 100 C) to eliminate contamination.
- Composition: bovine (cow) bone
- Approval: 510(k)
- MOA: Osteoconductive
Key Questions to Ask When Categorizing Bone Graft Fusion Material
1. What is bone graft technology’s composition?
- Mineral (synthetic)
- Donor bone and tissue (allograft)
- Recombinant protein (rhBMP)
2. What is the technology’s MOA?
- Osteogenesis: Living cells, such as osteoblasts, that form new bone
- Osteoconduction: Passive scaffold to maintain space and allow for bone formation
- Osteoinduction: Active recruitment and stimulation of stem cells, which differentiate into osteoblasts and form bone
3. How was the technology approved/cleared and for what indication?
- 510(k) clearance for formulated DBMs, synthetics, and biocomposites
- Human cellular and tissue products (HCT/Ps) that meet FDA criteria for regulation solely under 21 CFR Part 1271 regulations for HCT/Ps are not regulated as medical devices, and as such do not require 510(k) clearance.
- PMA/HDE approval for rhBMPs
4. What type of performance data are required for FDA approval/clearance?
- Preclinical: Rat, rabbit, dog, sheep, or monkey data
- Clinical: Human data