Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties.

All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10)

Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in trends toward decreased cartilage cross-sectional area and increased osteoclast density in woven bone versus physically rehabilitated mice.

In support of our hypothesis, physical remobilization increases callus bone formation following fracture compared to continued disuse potentially due to increased endochondral ossification and decreased bone resorption. In all, partial weight-bearing exercise immediately following fracture may improve callus healing compared to delayed rehabilitation regimens that are frequently used.

Bone regeneration is a complicate biological process of the skeletal system leading to restoration of the limb function. This process becomes more challenging in a case of critical size defect (CSD) which defined as the smallest defect caused by infection, tumor or trauma that will not heal spontaneously.

A previous study in our lab tested the usage of encapsulating Ethyl Cellulose (Hercules Inc, Wilmington, Del) membrane in CSD as compared to control (no-membrane). The study demonstrated that bone healing was more sufficient in limbs coated with the membrane than the control limbs. Additional approach to the treatment of bone deficiency is the use of multi-potent mesenchymal stem cells (MSC) that are brought into the bone defect in order to induce bone formation.

The objective of this study was to investigate a new polymer formulation in order to produce the best environmental support for adhesion, proliferation and differentiation of MSC.

In this study we found out that with the usage of Polyvinylacetate, PMMC R and PMMC L in PMMC RL PEG 400 [15%], MSC had similar characters to the polystyrene ( a well known ideal platform for MSC). This positive result permitted apparently thanks to creation abilities of:

Hydrogen-bonds between MSC and the partial negative charge on the carboxyl group as well as on the oxygens of the plasticizer that is intertwined within the membrane monomers.

In summary, we have only started to reveal the remarkable potential of using MSC, and there are still many obstacles to overcome. However, applying the findings from this study, namely inserting a membrane coated with MSC into a CSD may become a true biological treatment option.

Severe bone loss in weight bearing bones is one of the main causes for morbidity in trauma victims. The use of guided bone regeneration in the treatment of such large defects has not yet been studied extensively. The aim of this study was to establish an accurate evaluation system, which will enable quantifying the compatibility of membranes to provide bone regeneration in a large middiaphyseal bone defect. In our longitudinal study on 16 rabbits we examined the new bone formation obtained in the vicinity of critical segmental defects (2.5 times the diameter of the bone) covered with tubular ethyl cellulose membranes. The contralateral limbs with the same bone defect served as the control group which was not treated by membranes. The healing process was followed up for eight weeks.

Bone analysis of the implanted and non-implanted bone defects and adjacent tissues was performed in order to evaluate the total area and the density of the regenerated new bone at the gap area. Computerized X-ray study showed newly formed bone as early as 14 days after membrane implantation within and around the radial defect compared with a typical creation of non-union in the contra-lateral non-implanted defects. The bone formation across the gap progressed until reconstruction of the defect occurred after 6–8 weeks. A slowdown in new bone formation was evident after 6 weeks according to the measurements of area size and density of the formed bone.

A parallel longitudinal histomorphological assessment of the process in the treated and non-treated bone defects was conducted. A characteristic process of osteogenic activity and new bone formation takes place inside the confined space and within the tissues around it. A typical modeling process with lytic changes in the different osteogenic fronts takes place from the second week post-implantation. These histological findings, corresponding with the radiological assessment, were summarized according to a scoring system which was constructed by the authors. The scoring was related to eight different zones which were defined within and around the osteotomy site.

This rabbit model clarifies the mechanism and provides quantification of guided bone regeneration. It can serve as a means to study the accelerated bone formation using different membranes in large segmental weight bearing bone defects.