Colloidal Gels with Extracellular Matrix Particles and Growth Factors for Bone Regeneration in Critical Size Rat Calvarial Defects

Abstract

Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement are promising for filling complex geometries in craniofacial bone regeneration applications. Colloidal materials have demonstrated modest clinical outcomes as bone substitutes in orthopedic applications, but limited success in craniofacial applications. As such, development of a novel colloidal gel will fill a void in commercially available products for use in craniofacial reconstruction. One likely application for this technology is cranial reconstruction. Currently, traumatic brain injury (TBI) is often treated with a hemi-craniectomy, a procedure in which half the cranium is removed to allow the injured brain to swell and herniate beyond the enclosed cranial vault. The use of colloidal gels would allow for the design of a pliable material capable of expansion during brain swelling and facilitate cranial bone regeneration alleviating the need for a second surgery to replace the previously removed hemi-cranium. In the current study, colloidal nanoparticles of hydroxyapatite (HAp), demineralized bone matrix (DBM), and decellularized cartilage (DCC) were combined with hyaluronic acid (HA) to form colloidal gels with desirable rheological properties ([Formula: see text] ≥ 100 Pa). BMP-2 and VEGF growth factors were included to assess extracellular matrix (ECM) contribution of DBM and DCC. The HA-HAp (BMP-2) and HA-HAp-DCC group had 89 and 82% higher bone regeneration compared to the sham group, respectively (p < 0.01). Material retention issues observed may be alleviated by implementing chemical crosslinking. Overall, DCC may be a promising material for bone regeneration in general, and colloidal gels may hold significant potential in craniofacial applications.

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

“…Reprinted by permission from Macmillan Publishers Ltd: Nature Communications, Ref. 101, copyright 2014 3.5.1 | Hydrogels Townsend et al combined HA, hyaluronic acid, and DCC dECM parti-cles in PBS to fabricate a colloidal suspension with a paste-like consistency that was shown to enhance bone regeneration in vivo 111. Cartilage dECM particles have also been incorporated in type I collagen gels and have shown to enhance chondrogenic gene expression from MSCs encapsulated within the gels.…”

Hybrid scaffolds of Mg alloy mesh reinforced polymer/extracellular matrix composite for critical-sized calvarial defect reconstruction

“…DBM has been frequently evaluated for the repair of rat calvarial defects (Acarturk & Hollinger, ; Rhee et al, ; Townsend et al, ). Generalizing across studies, DBM was associated with a positive effect, but the efficacy of DBM alone was limited.…”

“…This may be attributable to the porous structure of this scaffold, the osteogenic efficacy of canine DBM, or possibly the DBM loading strategy that benefit to the release of bioactive agents. Commonly used strategies to improve the osteogenic efficacy of DBM have been to incorporate additional bioactive reagents, which include BMP‐2 (Townsend et al, ), the stromal vascular fraction cells (Rhee et al, ), and others. Comparing with DBM that has been combined with BMP‐2 (Townsend et al, ), Mg alloy mesh reinforced PLGA/DBM scaffold in this study had a lower osteogenic efficacy, which can be attributed to the recognized osteogenic efficacy of BMP‐2.…”

“…Commonly used strategies to improve the osteogenic efficacy of DBM have been to incorporate additional bioactive reagents, which include BMP‐2 (Townsend et al, ), the stromal vascular fraction cells (Rhee et al, ), and others. Comparing with DBM that has been combined with BMP‐2 (Townsend et al, ), Mg alloy mesh reinforced PLGA/DBM scaffold in this study had a lower osteogenic efficacy, which can be attributed to the recognized osteogenic efficacy of BMP‐2. In addition, DBM combined with polymer in some cases has a slower bone regeneration rate compared with DBM alone (Rhee et al, ), which may be due to the acidic degradation products of the polymer component aggravating local inflammatory reactions.…”

Recent Advances in Musculoskeletal Tissue Regeneration

“…In the area of new materials for scaffolds for tissue regeneration, Elisseeff and colleagues show that a micronized porcine urinary bladder matrix can be used to reduce osteoarthritis induced by anterior cruciate ligament transection in mice (12). Berkland and colleagues show that colloidal gels composed of colloidal nanoparticles of hydroxyapatite, demineralized bone matrix, decellularized cartilage, and hyaluronic acid combined with bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor generated significantly more bone in critical-sized rat calvarial defects than sham controls (13). In terms of evaluating the potential of controlled release of agents from scaffolds that can modulate and promote tissue repair, Livingston Arinzeh and colleagues show that controlled release of vanadium can stimulate mesenchymal stem cell osteochondrogenesis.…”