PAD®
Demineralization Technology

Optimized osteoinductivity to support bone healing.

PAD technology provides predictable osteoinductive potential compared to other DBMs because it precisely manages the demineralization process to target the ideal residual calcium of 2%.1,2,3,5,8,14,16,20,21

 

 

REDUCES CONTAMINATION

through use of a closed system8,15

 

OPTIMIZES OSTEOINDUCTIVE POTENTIAL

by targeting residual calcium level of 2%1,2,3,5,8,14,16,20,21

 

CONSISTENT AND PRECISE

 by adhering to graft type8,14,15,16,17

Reducing Contamination

PAD utilizes a fully automated, closed-vessel, computer-controlled system that minimizes technical errors and potential contamination of the final biomaterial. In contrast, conventional demineralization methods can lead to contamination due to frequent open-vessel acid changes or insufficient volumes of acid, which may create inconsistencies in the demineralization process.8,15

PAD targets optimal demineralization without denaturing important growth factors such as bone morphogenetic proteins (BMPs). The timing of acid exposure is tightly controlled to minimize any potential denaturing effects.8,14,15,18

 

Optimizing Osteoinductive Potential

The AATB standard for demineralization is a residual calcium level of less than 8%, which is well above the optimal level of 2%, as verified by both in vitro and in vivo testing. This disparity can lead to variability in the osteoinductive potential of various commercially available DBMs. Demineralization processes can differ significantly from manufacturer to manufacturer, impacting clinical performance.1,2,3,10,11,13,14,15,16,19 

LifeNet Health stands out as the only tissue processor capable of claiming optimal osteoinductivity for demineralized bone allografts, consistently targeting a 2% residual calcium level.8

 

Consistency and Precision

The PAD process is specifically designed for biocompatibility and predictability across various graft types. Allografts are processed into their final form prior to demineralization. Reagent delivery concentrations, volumes, and times are strictly controlled using a computer-controlled pump, enabling standardized and consistent demineralization tailored to each graft type. Additionally, to ensure the biocompatibility of the allograft bio-implant, the PAD process includes pH testing to confirm acid neutralization and analyses of samples to ensure proper residual calcium levels.8,14,15,16,17

 

PAD Peer-Reviewed Publications and Clinical Case Studies

PAD-processed allografts provide a biocompatible osteoconductive scaffold essential for bone remodeling. Both internal and independent pre-clinical results have shown that PAD-processed DBMs create a suitable microenvironment for bone marrow-derived mesenchymal stem cell (BM-MSC) attachment, survival, and metabolic activity.1,2,3,7,18,20

PAD Technology: Osteoinductive Potential of PAD-Processed Allografts

PAD Technology: Osteoinductive Potential of PAD-Processed Allografts23

Pre-clinical testing has demonstrated the promising osteoinductive potential of PAD-processed allografts in an in vivo model using athymic rodents. The histological analysis from this study provides compelling evidence of 50% new bone formation within the implant scaffold, highlighting key components essential for effective bone regeneration. 

Findings from the histology include:

  • New bone formation
  • Bone marrow development
  • New blood vessels
  • Cartilage presence
  • Chondrocytes

These results affirm that the osteoinductive properties of the demineralized bone matrix (DBM) are preserved, encouraging bone growth even in atypical environments, such as muscle tissue where bone typically does not develop. This innovative technology paves the way for enhanced healing and regeneration in orthopedic applications, promising significant advancements in patient outcomes. 

Pre-Clinical Testing: Variability between Demineralized Bone Matrix (DBM) Products

Pre-Clinical Testing: Variability between Demineralized Bone Matrix (DBM) Products5

Pre-clinical testing has highlighted significant variability in the performance of different demineralized bone matrices (DBMs). A notable study conducted in 2013 utilized an animal model to explore this variability, comparing LifeNet Health’s demineralized freeze-dried bone allograft (DFDBA) with Osteotech’s DBM.

In this study, researchers employed Wistar rats to evaluate the osteoinductive potential of each DBM. A 3 mm hole was drilled into the femurs of 37 rats and filled with 10 mg of either DBM, while another set served as a control without any DBM implantation. The results were compelling: at 4 and 8 weeks post-implantation, micro-computed tomography revealed that the PAD-processed DBM exhibited greater bone formation. This finding underscores the advantages of the PAD process and demonstrates the distinct differences in bone healing properties among DBMs sourced from various producers.

What sets PAD apart from other demineralization techniques is its targeted approach to achieving an optimal residual calcium level of 2%. This careful calibration promotes consistency in results, making it a superior choice for enhancing bone regeneration.  

The authors of the study concluded that LifeNet Health’s DBM significantly supported new bone formation due to its enhanced osteoinductive properties. Such evidence highlights the importance of choosing the right DBM to maximize the potential for successful bone healing. 

Other Peer-Reviewed Publications

Zhang M, Powers RM Jr, Wolfinbarger L Jr. Effect(s) of the demineralization process on the osteoinductivity of demineralized bone matrix. J Periodontol. 1997 Nov;68(11):1085-92. doi: 10.1902/jop.1997.68.11.1085

Turonis JW, McPherson JC 3rd, Cuenin MF, Hokett SD, Peacock ME, Sharawy M. The effect of residual calcium in decalcified freeze-dried bone allograft in a critical-sized defect in the Rattus norvegicus calvarium. J Oral Implantol. 2006;32(2):55-62. doi: 10.1563/780.1

Miron RJ, Zhang Q, Sculean A, Buser D, Pippenger BE, Dard M, Shirakata Y, Chandad F, Zhang Y. Osteoinductive potential of 4 commonly employed bone grafts. Clin Oral Investig. 2016 Nov;20(8):2259-2265. doi: 10.1007/s00784-016-1724-4

Wei L, Miron RJ, Shi B, Zhang Y. Osteoinductive and Osteopromotive Variability among Different Demineralized Bone Allografts. Clin Implant Dent Relat Res. 2015 Jun;17(3):533-42. doi: 10.1111/cid.12118

McLean JB, Carter N, Sohoni P, Moore MA. Cell attachment and osteoinductive properties of tissue engineered, demineralized bone fibers for bone void filling applications. Clinical Implementation of Bone Regeneration and Maintenance, IntechOpen. 2021. doi:10.5772/intechopen.88290

Herold RW, Pashley DH, Camuenin MF, Niagro F, Hokett SD, Peacock ME, Mailhot J, Borke J. The effects of varying degrees of allograft decalcification on cultured porcine osteoclast cells. J Periodontol. 2002 Feb;73(2):213-9. doi: 10.1902/jop.2002.73.2.213

 

References

  1. Zhang M, Powers RM Jr, Wolfinbarger L Jr. Effect(s) of the demineralization process on the osteoinductivity of demineralized bone matrix. J Periodontol. 1997 Nov;68(11):1085-92. doi: 10.1902/jop.1997.68.11.1085
  2. Turonis JW, McPherson JC 3rd, Cuenin MF, Hokett SD, Peacock ME, Sharawy M. The effect of residual calcium in decalcified freeze-dried bone allograft in a critical-sized defect in the Rattus norvegicus calvarium. J Oral Implantol. 2006;32(2):55-62. doi: 10.1563/780.1
  3. Herold RW, Pashley DH, Camuenin MF, Niagro F, Hokett SD, Peacock ME, Mailhot J, Borke J. The effects of varying degrees of allograft decalcification on cultured porcine osteoclast cells. J Periodontol. 2002 Feb;73(2):213-9. doi: 10.1902/jop.2002.73.2.213
  4. Miron RJ, Zhang Q, Sculean A, Buser D, Pippenger BE, Dard M, Shirakata Y, Chandad F, Zhang Y. Osteoinductive potential of 4 commonly employed bone grafts. Clin Oral Investig. 2016 Nov;20(8):2259-2265. doi: 10.1007/s00784-016-1724-4
  5. Wei L, Miron RJ, Shi B, Zhang Y. Osteoinductive and Osteopromotive Variability among Different Demineralized Bone Allografts. Clin Implant Dent Relat Res. 2015 Jun;17(3):533-42. doi: 10.1111/cid.12118
  6. McLean JB, Carter N, Sohoni P, Moore MA. Cell attachment and osteoinductive properties of tissue engineered, demineralized bone fibers for bone void filling applications. Clinical Implementation of Bone Regeneration and Maintenance, IntechOpen. 2021. doi:10.5772/intechopen.88290
  7. Gianulis E, Wetzell B, Scheunemann D, et al. Characterization of an advanced viable bone allograft with preserved native bone-forming cells [published online ahead of print, 2022 Nov 25]. Cell Tissue Bank. 2022;10.1007/s10561-022-10044-2. doi:10.1007/s10561-022-10044-2
  8. PAD Patents 6,189,537; 6,534,095; 6,189,537; and 6,305,379
  9. Allowash patents 6,024,735; 5,977,034; 5,976,104; 5,820,581; 5,797,871; and 5,556,379  
  10. Musculoskeletal Tissue Regeneration: Biological Materials and Methods. Ed. Pietrzak WS. 2008 Springer, p. 100.
  11. Reddi AH, Huggins C. Biochemical sequences in the transformation of normal fibroblast in adolescent rats. Proc Natl Acad Sci 1972;69:1601-1605  
  12. Urist MR, Strates BS. The classic: Bone morphogenetic protein. Clin Orthop Relat Res. 2009 Dec;467(12):3051-62. doi: 10.1007/s11999-009-1068-3.
  13. Mott DA, Mailhot J, Cuenin MF, Sharawy M, Borke J. Enhancement of osteoblast proliferation in vitro by selective enrichment of demineralized freeze-dried bone allograft with specific growth factors. J Oral Implantol. 2002;28(2):57-66.
  14. FAQ: PAD Demineralization Technology
  15. FAQ: What is Pulse Acidification Demineralization (PAD) Technology?
  16. PowerPoint: Optimized Demineralization: The Power of PAD
  17. PowerPoint: Processing Matters
  18. ISO-10993-5 Cytotoxicity Testing of Gamma Irradiated Ground Cortical and Demineralized Bone
  19. Effects of Residual Calcium Content in Demineralized Bone Matrix Fibers on Osteoinductive Potential in vivo
  20. Cell Interaction of Bone Marrow Derived Mesenchymal Stem Cells Seeded onto Compressed Demineralized Cortical Fiber Chips
  21. Assessment of the Osteoinductive Potential of Optium Gel after Expiration of Current Shelf Life
  22. Effects of Gamma Irradiation on the Osteoinductive Potential of Demineralized Bone Matrices in an Athymic Rat Posterolateral Spinal Fusion Model
  23. Gaskins B, Masinaei L, Moore MA, Wolfinbarger L. Osteoinductivity of Gamma-irradiated Demineralized Bone Matrix in the Nude Mouse Bioassay. AATB 30th Meeting, 2006.