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The ability to locally deliver bioactive molecules to distinct regions of the skeleton may provide a novel means by which to improve fracture healing, treat neoplasms or infections, or modulate growth. In this study, we constructed single-sided mineral-coated poly-ε-caprolactone membranes capable of binding and releasing transforming growth factor beta 1 (TGF-β1) and human growth hormone (hGH). After demonstrating biological activity in vitro and characterization of their release, these thin bioabsorbable membranes were surgically implanted using an immature rabbit model. Membranes were circumferentially wrapped under the periosteum, thus placed in direct contact with the proximal metaphysis to assess its bioactivity in vivo. The direct effects on the metaphyseal bone, bone marrow, and overlying periosteum were assessed using radiography and histology. Effects of membrane placement at the tibial growth plate were assessed via physeal heights, tibial growth rates (pulsed fluorochrome labeling), and tibial lengths. Subperiosteal placement of the mineralized membranes induced greater local chondrogenesis in the plain mineral and TGF-β1 samples than the hGH. More exuberant and circumferential ossification was seen in the TGF-β1 treated tibiae. The TGF-β1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups. While the proximal tibial growth plates were taller in the hGH treated than TGF-β1, no differences in growth rates or overall tibial lengths were found. In conclusion, these data demonstrate the feasibility of using bioabsorbable mineral coated membranes to deliver biologically active compounds subperiosteally in a sustained fashion to affect cells at the insertion site, bone marrow, and even growth plate., (© 2024 Wiley Periodicals LLC.)

Background: Guided growth corrects pediatric limb deformity by inhibiting growth on the convexity of the bone. Both modular and rigid implants have been used; we endeavor to determine whether a clear advantage of one implant exists. We further hypothesize that improved correction could be realized by accelerating growth with resection of the periosteum., Methods: Sixteen lambs underwent guided growth of the medial proximal tibia (the opposite limb served as a control). Group 1 used a rigid staple (n=5); group 2 a modular plate and screw construct (n=5), and group 3 had a similar device plus periosteal resection (n=6). Radiographs tracked the progression of deformity in the coronal plane. Before sacrifice, pulsed fluorochrome labels allowed for temporal and spatial growth rate analysis. At sacrifice, True Deformity was calculated (and compared with control tibia) from standardized radiographs in the coronal and sagittal planes. Device Efficiencies were normalized by dividing True Deformity produced (degrees) by the Expected Growth gain (mm) from the control limb., Results: Group 3 produced greater coronal plane deformity than group 1 by an average of 2.2 degrees per month (P=0.001) and group 2 by an average of 2.4 degrees per month (P=0.0007). At sacrifice, groups 1 and 2 were equally effective at limiting growth to 75% of control; no differences in growth retardation were noted. No differences in Device Efficiency were noted between groups 1 and 2. The Device Efficiency was significantly different between groups 1 and 2 with comparison with group 3 (P=0.05 and P=0.022); with a 2.5 degree/mm faster deformation in the stripped cohort., Conclusions: Rigid implants initially produced deformity quicker than modular constructs; yet ultimately, both implants were equally effective at guiding growth. Device Efficiency for the modular group improved significantly with the addition of periosteal stripping as method to accelerate growth.

Background: Disruption of the periosteum has been used to explain overgrowth after long bone fractures. Clinically, various periosteal procedures have been reported to accelerate growth with varied results. Differences between procedures and study populations, in these prior studies, make drawing conclusions regarding their effectiveness difficult., Questions/purposes: The purpose of this study was to (1) determine if all reported periosteal procedures accelerate growth and increase the length of bones; (2) study the relative duration of these growth-accelerating effects at two time points; and (3) identify the periosteal procedure that results in the most growth., Methods: Periosteal stripping (N = 8), periosteal transection (N = 8), periosteal resection (N = 8), (and) full periosteal release (N = 8) were performed on the tibiae of skeletally immature rabbits. Tibiae were collected 2 weeks postoperatively. The tibiae of additional cohorts of periosteal transection (N = 8), periosteal resection (N = 8), full periosteal release (N = 8), and repetitive periosteal transection (N = 8) were collected 8 weeks postoperatively. The contralateral tibiae served as an operative sham control in all cohorts. Fluorochrome bone labeling was used to measure growth rates, whereas high-resolution Faxitron imaging was performed to measure tibial lengths. Comparisons were then made between (1) experimental and sham controls; and (2) different procedures. Eight additional nonsurgical animals were included as age-matched controls., Results: Growth (in microns) was accelerated at the proximal tibial physis on the tibia undergoing the periosteal surgical procedures versus the contralateral control limb after the transection (411 ± 27 versus 347 ± 18, p < 0.001 [mean ± SD]), resection (401 ± 33 versus 337 ± 31, p < 0.001), and full periosteal release (362 ± 45 versus 307 ± 33, p < 0.001), 2 weeks after the index procedure. Conversely, the periosteal stripping cohort trended toward less growth (344 ± 35) than the controls (356 ± 25; p = 0.08). No differences were found between limbs in the nonoperative controls. Tibial lengths for the experimental tibiae were longer at 2 weeks in the transection (1.6 ± 0.4 mm, p < 0.001), resection (1.6 ± 0.9 mm, p = 0.03), and full periosteal release (1.7 ± 0.5 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (0.13 ± 0.7 mm, p = 0.8) and stripping cohorts (0.10 ± 0.6 mm, p = 0.7). At 8 weeks, growth acceleration ceased at the proximal tibial physes in the transection cohort (174 ± 11 versus 176 ± 21, p = 0.8), and the control limbs actually grew faster than the experimental limbs after resection (194 ± 24 versus 178 ± 23, p = 0.02) and full periosteal release (193 ± 16 versus 175 ± 19, p < 0.01) cohorts. Growth rates were increased over control limbs, only in the repetitive transection cohort (190 ± 30 versus 169 ± 19, p = 0.01) at 8 weeks. Tibial lengths for the experimental tibiae remained longer at 8 weeks in the transection (1.4 ± 0.70 mm, p < 0.001), resection (2.2 ± 0.82 mm, p < 0.001), full periosteal release (1.6 ± 0.42 mm, p < 0.001), and repetitive periosteal transection (3.3 ± 1.1 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (-0.08 ± 0.58 mm, p = 0.8). Comparing the procedures at 2 weeks postoperatively, no differences were found in tibial lengths among the transection (2.1% ± 0.5% increase), resection (2.1% ± 1.1% increase), and full periosteal release (2.1% ± 0.6 %); however, all three demonstrated greater increased growth when compared with the stripping cohort (-0.10% ± 0.7%; p < 0.05). At 8 weeks no differences could be found between increased tibial lengths among the transection (1.5% ± 0.7%), resection (2.3% ± 0.9%), and full periosteal release (1.7% ± 0.4%). The repetitive transection produced the greatest over length increase (3.5% ± 1%), and this was greater than the acceleration generated by the single resection (p < 0.001) or the full periosteal release (p = 0.001). All four demonstrated an increase greater than the nonoperative control (0.09% ± 0.6%; p < 0.05)., Conclusions: Transection of the longitudinally oriented periosteal fibers appears critical to accelerate growth in a rabbit model., Clinical Relevance: These findings in an animal model support previous claims that limb overgrowth occurs as the result of periosteal disruption. Based on these findings in rabbits, we believe that less invasive procedures like periosteal transection are a promising avenue to explore in humans; clinical studies should seek to determine whether it is equally effective as more invasive procedures and its role as an adjunct to guided growth or distraction osteogenesis.