10 Common FAQ about PLLA/HA and Bone Regeneration

Post written by : Wong Yuen Lam

1. What is the expected rate of degradation with PLLA/HA materials?

For degradation time , According to Fig. 1, PLLA loses 90–93% of its inherent viscosity by week 52 in vivo. However, this molecular breakdown is distinct from complete resorption. High-molecular-weight PLLA typically requires 2 to 5.5 years for complete structural clearance and resorption.

Fig 1. displays the degradation profiles of bioabsorbable PLLA spinal fusion cages measured by changes in inherent viscosity  over a period of 72 weeks in vivo and in vitro.("S") The stiff PLLA cage (axial compression stiffness: 4 kN/mm; strength: 6.7 kN) was designed with a wall thickness of 1.5 mm ("F") the flexible PLLA cage (axial compression stiffness: 2 kN/mm; strength: 2.5 kN) with a wall thickness of 0.75 mm both types of spinal fusion cages has the same exterior geometrical dimensions (10 × 10 × 18 mm). (1)

Meanwhile, adding HA would accelerate the degradation. Wang et.al's study show that incorporating HA significantly accelerates the breakdown of the polymer matrix compared to pure PLLA. As tracked by viscosity-average molecular weight (Mv), pure PLLA maintains a slower, more gradual degradation profile, retaining a higher molecular weight through 36 weeks. In contrast, both nano-hydroxyapatite (n-HAP/PLLA) and grafted-hydroxyapatite (g-HAP/PLLA) composites experience a much sharper drop in molecular weight, ultimately reducing down to 14-16 kDa by week 36. This accelerated degradation highlights how the hydrophilic nature of HA and its ion-exchange properties facilitate faster water penetration and structural turnover, making composite scaffolds highly effective for progressive bone-substitution applications.

Fig 2. comparison between PLLA and HA-PLLA degradation rate (2)

2. Question: What is the expected extent of bone regeneration comparing PLLA and PLLA/HA materials?

While PLLA provides structural integrity, HA acts as an osteoconductive signal and buffers acidic degradation products, active bone regeneration and osteointegration occur within 6 to 12 months, which is well before total PLLA bioabsorption. (3)

Zhang et al. demonstrated that incorporating HA into PLLA scaffolds significantly enhances cell proliferation, adhesion, and overall bone regeneration. As illustrated in Figure 3, in vivo evaluation at 4 weeks revealed that scaffolds containing 50% nHA were extensively infiltrated with new bone tissue. Furthermore, histological findings showed an organized distribution of osteocytes and the formation of Haversian canals, indicating advanced tissue maturity. Notably, the newly formed bone established a seamless, tightly bound interface directly with the scaffold surface.

Fig 3. Implanted in rabbit for in-vivo testing of the new bone growth for a 50%HA/PLLA scaffold

3 . Question: How does the material interact with the surrounding bone during implantation and degradation?

During the early stage after implantation, partial dissolution of CaP ceramic macrocrystals increases the concentrations of calcium and phosphate ions in the local environment. The subsequent sequence of events (e.g., mesenchymal stem cell migration to the surface layer, induction of mesenchymal stem cell differentiation into osteoblasts, and activation and regulation of osteogenic gene expression in these cells) leads to new bone formation around the material. The bioactive and bioresorbable unsintered hydroxyapatite (u-HA) particles are then resorbed into the surrounding natural bone, where they show strong osteoconductivity without the onset of physical irritation.

The resorption of u-HA particles on the surface of the porous composites leads to increased water uptake, which may accelerate PLLA hydrolysis. Uniform hydrolysis occurs throughout the thin PLLA film matrices, results in the steady release of small amounts of debris as the materials degrade. 

After 2.5 years, Mv decreased to <50KDa and mechanical strength was almost lost. The implant size remarkably contracted after 3.5 years and no residual PLLA was detected in the composites after 4.5 years.

Fig 4. chart illustrates the long-term degradation mechanism and bone-substitution process of an uncalcined hydroxyapatite/poly-L-lactic acid (u-HA/PLLA) composite over a 6-year timeline. (4)

4 . Question: On which side does bone regeneration primarily occur – from the surrounding native bone toward the implant, from within the implant, or from both sides?

For the direction of advancement (across defect), the bone tissue progresses inward from the host bone margins to bridge the gap. While for direction of thickening (at the interface), once the bone cells attach and start mineralization at the implant boundary (as shown in 5B), that individual layer of new bone thickens by growing outward from the implant wall. (5)

Fig 5A (Left) Macro-Level Site-- Shows an overview of the reconstructive bone site

Fig 5B( Right) (Micro-Interface & Ion Exchange): Magnifies the boundary where body fluid interacts with the u-HA/PLLA device.

5 . Question: For a cranial bone defect of approximately 10*10 mm, what level of bone regeneration can be expected?

As the implant degrades and new bone forms, can the regenerated bone eventually achieve mechanical strength comparable to the original surrounding bond?

As shown by a research conducted by Fan et.al, a 3D printed (HA-PLA) composites in repairing cranial defects (with a diameter of approximately 1 cm) were evaluated in a rabbit experimental model, with autologous bone powder is used as a comparison. The result show that the experimental group, the defect was roughly observed with the naked eye to have been mostly filled with new bone tissue and fibrous tissue, forming an integral whole with the surrounding normal bone tissue. Also, there was no statistically significant difference in the microhardness of the repaired area from the 3D printed HA-PLA composite compared with that of the repaired area from autologous bone powder and of the normal bone. (6)

Fig 6. Healing of cranial defects in rabbits at 30 days (a)(b) and 90 days (c)(d)

6 . Question: If the defect is segmented into multiple smaller sections, how would this affect bone-to-bone (B-B) and implant-to-bone (I-B) interactions?

Segmenting a large bone defect into smaller, manageable sections can significantly influence both bone-to-bone (B–B) and implant-to-bone (I–B) interactions. When the defect is divided, each segment can heal more effectively due to better vascularization, improved stabilization, and localized osteogenic activity (Hollister et al., 2010). This segmentation facilitates incremental bone regeneration, promoting more predictable remodelling and integration. (7)

Dividing the defect allows for focused regeneration within smaller zones, reducing the likelihood of complications such as delayed union or non-union that are more common in large, critical-sized defects. Smaller segments encourage faster and more robust B–B healing through enhanced cellular migration and mineralization. (8)

Segmented defects can improve implant stability by allowing for better fitting of grafts or scaffolds within each section, which reduces micro-movement and enhances osseointegration. Moreover, segmenting the defect allows for staged or localized support, which can optimize implant-bone contact and accelerate overall healing.(9)

7. Question: What is the average defect size with clinical evidence supporting the use of PLLA/HA material?

For range of defect size, the clinical case series evaluated patients with extensive skull base bony defects ranging from 25 mm to 50 mm (with a mean defect size of 32.1 mm). Using the unsintered hydroxyapatite (u-HA)/PLLA plate as part of a rigid multilayer reconstruction successfully prevent postoperative CSF leaks in all patients, with no reported material-related complications. (10)

8.⁠ ⁠Question: Is there any difference in the rate or quality of bone regeneration when the implant is in contact with cortical bone versus cancellous bone?

The Cancellous bone's spongy structure provides unique advantages for the biological aspects of implant integration. The numerous spaces within this bone type contain an abundant blood supply, which facilitates faster healing and more efficient delivery of nutrients and healing factors to the implant site.The increased vascularity of cancellous bone promotes more rapid bone remodelling and regeneration around the implant surface. This enhanced biological activity often leads to faster osseointegration, although the initial mechanical stability may be lower compared to dense cortical bone placements.

Meanwhile, the density that makes cortical bone so strong present certain challengesin bone regneration. The compact structure contains fewer blood vessels compared to cancellous bone, which may result in slower healing and longer osseointegration periods(11).

9. Question: If the implant is used primarily for cosmetic reconstruction and is not subjected to significant mechanical loading, is bone regeneration still expected?

Yes, the lack of mechanical stimulation typically impairs bone regeneration, but the addition of HA can compensate by providing essential chemical and biological mechanisms.

Without mechanical loading, the mechanosensitive pathway (like Piezo1) is not actively driven by physical force, meaning you lose the primary mechanical “accelerator” for bone anabolism.(12)

Fig 7 .Bone volume per tissue volume (BV/TV) measured in the femur and the L4 vertebra of 12-week-old female Dmp1-Cre; Piezo1^f/f (n = 9) (KO) and Piezo1^f/f (n = 7) mice.

However, When the implant contains Hydroxyapatite (HA), it can still encourage localized bone regeneration through osteoconduction and ion-mediated bioactivity (releasing calcium and phosphate), allowing cells to attach and form a mineralized matrix even when mechanical forces are low or absent.

10. Questions: Has the material been evaluated for mandibular/ lower-jawbone defects?

Ueki et al. reviewed clinical outcomes in patients with mandibular prognathism, comparing those treated with a unsintered hydroxyapatite (u-HA)/PLLA plate system versus a titanium group following sagittal split ramus osteotomy (SSRO). The findings indicated no significant technical difficulties with the u-HA/PLLA system compared to titanium hardware, though minor positional shifts were observed, including a significantly greater change in the right condyle angle between baseline and 1 month, as well as in the intercondylar axes angle between 1 and 3 months. (13)

As outlined in the narrative review by Ngo et al., bioresorbable uncalcined PLLA/HA devices have expanded beyond standard fracture fixation into several specialized applications within oral and maxillofacial surgery:

1. Orbital Wall Fracture: u-HA/PLLA sheets and plates are used to reconstruct delicate orbital floors and walls, providing rigid support to prevent complications such as enophthalmos while safely integrating with surrounding tissues.

2. Le Fort I Osteotomy: Resorbable miniplates and screws made of u-HA/PLLA provide stable internal fixation following midface maxillary repositioning and advancement procedures, eliminating the need for a second surgery to remove hardware.

3. Maxillary Sinus Lift in an Atrophic Maxilla: u-HA/PLLA devices and composite materials serve as structural scaffolds and barriers in ridge augmentation and sinus floor elevation procedures, facilitating osteoconduction and predictable new bone formation in deficient maxillary bone. (14)

Reference

1. Van Dijk, M., Tunc, D.C., Smit, T.H., Higham, P., Burger, E.H. and Wuisman, P.I.J.M. (2002), In vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages. J. Biomed. Mater. Res., 63: 752-759. https://doi.org/10.1002/jbm.10466

2. Wang, Z., Wang, Y., Ito, Y. et al. A comparative study on the in vivo degradation of poly(L-lactide) based composite implants for bone fracture fixation. Sci Rep 6, 20770 (2016). https://doi.org/10.1038/srep20770

3. Boqing Zhang, Ling Wang, Ping Song, Xuan Pei, Huan Sun, Lina Wu, Changchun Zhou, Kefeng Wang, Yujiang Fan, Xingdong Zhang, 3D printed bone tissue regenerative PLA/HA scaffolds with comprehensive performance optimizations, Materials & Design, Volume 201, 2021, https://doi.org/10.1016/j.matdes.2021.109490

4. Yasuo Shikinami, Yoshitaka Matsusue, Takashi Nakamura, The complete process of bioresorption and bone replacement using devices made of forged composites of raw hydroxyapatite particles/poly l-lactide (F-u-HA/PLLA), Biomaterials, Volume 26, Issue 27, 2005, Pages 5542-5551, https://doi.org/10.1016/j.biomaterials.2005.02.016

5. Ngo, H. X., Bai, Y., Sha, J., Ishizuka, S., Toda, E., Osako, R., Kato, A., Morioka, R., Ramanathan, M., Tatsumi, H., Okui, T., & Kanno, T. (2022). A Narrative Review of u-HA/PLLA, a Bioactive Resorbable Reconstruction Material: Applications in Oral and Maxillofacial Surgery. Materials, 15(1), 150. https://doi.org/10.3390/ma15010150

6. Fan G, Yang L, Liu D, Wang Y, Ji W, Tukebai, Qin H, Wang Z. Repair of Cranial Defects in Rabbits with 3D-Printed Hydroxyapatite/Polylactic Acid Composites. Biomed Res Int. 2022 Dec 31;2022:7562291. doi: 10.1155/2022/7562291 

7. Hollister, S. J., et al. (2010). Scaffold design and fabrication. Nature Materials, 5(8), 631–644

8. Giannoudis, P. V., et al. (2011). The biology of fracture healing: an overview of current concepts. Injury, 42(3), 380–386.

9. Hollister, S. J., et al. (2010). Scaffold design and fabrication. Nature Materials, 5(8), 631–644

10. Manthawornsiri, K., Morisako, H., Nagahama, A., Ikegami, M., Hazunga, R., Liew, B. S., & Goto, T. (2025). Simple rigid skull base reconstruction with resorbable unsintered hydroxyapatite/poly-l-lactide plate in endoscopic endonasal skull base tumor surgery: illustrative case. Journal of neurosurgery. Case lessons, 10(14), CASE25544. https://doi.org/10.3171/CASE25544

11. Chakraverty, S. (n.d.). The difference between cortical and cancellous bone in implant dentistry. Dental Implants London. Retrieved August 31, 2026, from https://www.dental-implants-london.co.uk/blog/difference-between-cortical-cancellous-bone-implant-dentistry

12. Xuehua Li Li Han Intawat Nookaew Erin Mannen Matthew J Silva Maria Almeida Jinhu Xiong (2019) Stimulation of Piezo1 by mechanical signals promotes bone anabolism eLife 8:e49631., https://doi.org/10.7554/eLife.49631

13. Koichiro Ueki, Katsuhiko Okabe, Mao Miyazaki, Aya Mukozawa, Akinori Moroi, Kohei Marukawa, Kiyomasa Nakagawa, Etsuhide Yamamoto, Skeletal Stability After Mandibular Setback Surgery: Comparisons Among Unsintered Hydroxyapatite/Poly-L-Lactic Acid Plate, Poly-L-Lactic Acid Plate, and Titanium Plate, Journal of Oral and Maxillofacial Surgery, Volume 69, Issue 5, 2011, Pages 1464-1468, https://doi.org/10.1016/j.joms.2010.06.187.

14. Ngo, H. X., Bai, Y., Sha, J., Ishizuka, S., Toda, E., Osako, R., Kato, A., Morioka, R., Ramanathan, M., Tatsumi, H., Okui, T., & Kanno, T. (2022). A Narrative Review of u-HA/PLLA, a Bioactive Resorbable Reconstruction Material: Applications in Oral and Maxillofacial Surgery. Materials, 15(1), 150. https://doi.org/10.3390/ma15010150