Poly(lactide-co-ε-caprolactone) scaffold promotes equivalent tissue integration and supports skin grafts compared to a predicate collagen scaffold.

Dermal scarring from motor vehicle accidents, severe burns, military blasts, etc. is a major problem affecting over 80 million people worldwide annually, many of whom suffer from debilitating hypertrophic scar contractures. These stiff, shrunken scars limit mobility, impact quality of life, and cost millions of dollars each year in surgical treatment and physical therapy. Current tissue engineered scaffolds have mechanical properties akin to unwounded skin, but these collagen-based scaffolds rapidly degrade over 2 months, premature to dampen contracture occurring 6-12 months after injury. This study demonstrates a tissue engineered scaffold can be manufactured from a slow-degrading viscoelastic copolymer, poly(ι-lactide-co-ε-caprolactone), with physical and mechanical characteristics to promote tissue ingrowth and support skin-grafts. Copolymers were synthesized via ring-opening polymerization. Solvent casting/particulate leaching was used to manufacture 3D porous scaffolds by mixing copolymers with particles in an organic solvent followed by casting into molds and subsequent particle leaching with water. Scaffolds characterized through SEM, micro-CT, and tensile testing confirmed the required thickness, pore size, porosity, modulus, and strength for promoting skin-graft bioincorporation and dampening fibrosis in vivo. Scaffolds were Oxygen Plasma Treatment and collagen coated to encourage cellular proliferation. Porosity ranging from 70% to 90% was investigated in a subcutaneous murine model and found to have no clinical effect on tissue ingrowth. A swine full-thickness skin wound model confirmed through histology and Computer Planimetry that scaffolds promote skin-graft survival, with or without collagen coating, with equal safety and efficacy as a commercially available tissue engineered scaffold. This study validates a scalable method to create poly(ι-lactide-co-ε-caprolactone) scaffolds with appropriate characteristics and confirms in mouse and swine wound models that the scaffolds are safe and effective at supporting skin-grafts. The results of this study have brought us closer towards developing an alternative technology that supports skin grafts with the potential to investigate long-term hypertrophic scar contractures.

Osteogenic benefits of low-intensity pulsed ultrasound and vibration in a rodent osseointegration model.

OBJECTIVES: Osseointegrated prostheses are increasingly used for amputees, however, the lengthy rehabilitation time of these prostheses remains a challenge to their implementation. The aim of this study was to investigate the ability of locally applied vibration or low-intensity pulsed ultrasound (LIPUS) to accelerate osseointegration and increase peri-implant bone volume. METHODS: A 4-week and 8-week rodent study were conducted in a femoral intramedullary implant model (control, vibration, LIPUS, and combined treatment) to determine effects on healing. Osseointegration was evaluated quantitatively through mechanical, µCT and histological evaluations. RESULTS: Maximum pushout load at 4 weeks increased with LIPUS relative to control (37.7%, P=0.002). Histologically, LIPUS and vibration separately increased peri-implant bone formation after 4 weeks relative to control. Vibration resulted in greater peri-implant bone after 8 weeks than all other groups (25.7%, P<0.001). However, no significant group differences in pushout load were noted at 8 weeks. CONCLUSIONS: Although vibration increased bone around implants, LIPUS was superior to vibration for accelerating osseointegration and increasing bone-implant failure loads at 4 weeks. However, the LIPUS benefits on osseointegration at 4 weeks were not sustained at 8 weeks.

Bone changes after short-term whole body vibration are confined to cancellous bone.

OBJECTIVE: This study assessed femur properties in 80 adult female rats exposed to a range of whole body vibration amplitudes at 45 Hz over five weeks. Our hypothesis was that an optimal amplitude for whole body vibration would be apparent and would result in increased bone strength. METHODS: Animals were treated in five amplitude groups (0 g, 0.15 g, 0.3 g, 0.6 g, and 1.2 g peak), for 15 minutes per day, five days per week, for five weeks. Femur strength was assessed via: (1) three-point bending of the shaft, (2) cantilever bending of the neck, and (3) indentation of distal cancellous bone. Femoral bone mineral density, plasma prostaglandin E2 (PGE2) concentrations, cartilage thickness, and histopathologic properties were measured. RESULTS: Vibration doubled (P=0.039) cancellous bone stiffness in the 0.6 g and 1.2 g groups and induced a 74% increase in PGE2 concentrations (P=0.007). However, femoral densitometry and strength of the neck and shaft were unchanged and the cancellous bone indentation strength did not differ statistically (P=0.084). Cartilage thickness of vibrated groups at the medial condyle did not increase significantly (P=0.142) and the histopathologic grade did not change. There was no definitive optimal vibration amplitude. CONCLUSION: The benefits of vibration therapy over five weeks were confined to cancellous bone.

Local delivery of a zoledronate solution improves osseointegration of titanium implants in a rat distal femur model.

This study aimed to determine whether locally applied anti-resorptive agents acetazolamide or zoledronic acid would improve mechanical stability in implant osseointegration when applied as a solution within the medullary canal. Thirty-three rats received titanium-implants bilaterally in their intramedullary femoral canals. Prior to implantation, animals received 0.1 ml saline, 1 mM acetazolamide solution, or 0.7 mM zoledronic acid solution directly into the medullary cavity. The control group only received saline within the medullary canal while the treatment groups only received the respective treatment to which they were randomized. Animals were allowed to heal 4 weeks, at which time they were euthanized and femurs isolated for mechanical and radiographic evaluation. Push-out force to failure increased 152% in the zoledronic acid group relative to the control. There was no significant difference in push-out force with acetazolamide relative to control. Also, zoledronic acid increased metaphyseal bone volume fraction 46% and increased metaphyseal bone-implant contact 58% relative to the control. Recent research exploring local injection of medications to improve implant osseointegration and minimize systemic-effects has failed to quantitatively evaluate implant fixation strength on non-hydroxyapatite coated implants or implants without previous bone compaction. This study demonstrated that a simple injection of zoledronic acid into the medullary canal, rather than coatings or commercial gels, can increase fixation strength of an uncoated titanium-implant. Our findings indicate simple injection of zoledronic acid in saline solution has the potential for improving fixation of uncemented joint implants. Clinical Significance: Intramedullary injection of local bisphosphonate solutions could be implemented to improve osseointegration in cementless arthroplasty. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3294-3298, 2018.

Improved osseointegration with as-built electron beam melted textured implants and improved peri­implant bone volume with whole body vibration.

Transcutaneous osseointegrated prostheses provide stable connections to the skeleton while eliminating skin lesions experienced with socket prosthetics. Additive manufacturing can create custom textured implants capable of interfacing with amputees' residual bones. Our objective was to compare osseointegration of textured surface implants made by electron beam melting (EBM), an additive manufacturing process, to machine threaded implants. Whole body vibration was investigated to accelerate osseointegration. Two cohorts of Sprague-Dawley rats received bilateral, titanium implants (EBM vs. threaded) in their tibiae. One cohort comprising five groups vibrated at 45 Hz: 0.0 (control), 0.15, 0.3, 0.6 or 1.2 g was followed for six weeks. Osseointegration was evaluated through torsional testing and bone volume fraction (BV/TV). A second cohort, divided into two groups (control and 0.6 g), was followed for 24 days and evaluated for resonant frequency, bone-implant contact (BIC) and fluorochrome labeling. The EBM textured implants exhibited significantly improved mechanical stability independent of vibration, highlighting the benefits of using EBM to produce custom textured surfaces. Bone formation on and around the EBM textured implants increased compared to machined implants, as seen by BIC and fluorescence. No difference in torque, BIC or fluorescence among vibration levels was detected. BV/TV significantly increased at 0.6 g compared to control for both implant types.

Osseointegration of Coarse and Fine Textured Implants Manufactured by Electron Beam Melting and Direct Metal Laser Sintering.

Osseointegrated implants transfer loads from native bone to a synthetic joint and can also function transdermally to provide a stable connection between the skeleton and the prostheses, eliminating many problems associated with socket prostheses. Additive manufacturing provides a cost-effective means to create patient-specific implants and allows for customized textures for integration with bone and other tissues. Our objective was to compare the osseointegration strength of two primary additive manufacturing methods of producing textured implants: electron beam melting (EBM) (mean Ra = 23 µm) and direct metal laser sintering (DMLS) (mean Ra = 10 µm). Due to spatial resolution, DMLS can produce surfaces with a roughness comparable to EBM. Two cohorts of Sprague-Dawley rats received bilateral, titanium implants in their distal femurs and were followed for 4 weeks. The first-cohort animals received EBM implants transcortically in one femur and a DMLS implant in the contralateral femur. The second cohort received DMLS implants (either fine textured or coarse textured to mimic EBM) in the intramedullary canal of each femur. Osseointegration was evaluated through mechanical testing and micro-computed tomography (bone volume fraction [BV/TV] and bone-implant contact [BIC]). The fixation strength of coarse textured implants provided superior interlocking relative to fine textured implants without affecting BV/TV or BIC in both cohorts. Coarse EBM implants in a transcortical model demonstrated an 85% increase in removal torque relative to the fine DMLS textured implants. The thrust load in the intramedullary model saw a 35% increase from fine to coarse DMLS implants.