Endogenous Platelet-Rich Plasma Supplements/Augments Growth Factors Delivered via Porous Collagen-Nanohydroxyapatite Bone Substitute for Enhanced Bone Formation

Abstract

Polymer (acrylate) and ceramic bone cements are extensively used as bone void fillers and for implant fixation in orthopedics. These materials have micro- to nonporous architectures. Postimplantation, they may cause hypoxic and exothermic injuries to already compromised damage site. These materials also have limited interaction with surrounding tissue. In this work we have developed composite collagen-nanohydroxyapatite (CS) bone filler, mimicking porous architecture of trabecular bone. It was functionalized with clinically available bone active agents like bone morphogenetic protein-2 (rhBMP-2) and zoledronic acid (ZA). We investigated synergistic effects of the bone active molecules and endogenous platelet rich plasma (PRP), a source of growth factors on mineralization. Porous CS and collagen/gelatin/chiotosan polymer scaffold (SC) (without nanohydroxyapatite) were synthesized using cryogelation. PRP (10 μL) (∼5 × 106 cells), rhBMP-2 (5 μg) and ZA (10 μg) were used to functionalize scaffolds. Bone formation was evaluated at ectopic sites in abdominal pouch and 4.0 mm critical defect in tibia metaphysis of rats. Tissue mineralization was evaluated by micro-CT and histological analysis 12 weeks postimplantation. In vitro cell based studies revealed, PRP functionalization enhances osteoblast proliferation and activity on scaffolds. In vivo BMP+ZA+PRP functionalized scaffolds had higher amount (28 mm3) of mineralized tissue formation as compared to empty defect (20 mm3), suggesting that PRP can augment the osteoinductive properties of functionalized scaffolds both in vitro and in vivo. Enhanced cell infiltration and mineralization can be achieved via CS in comparison to SC, implying their use as porous bone void fillers and substitutes for autografts.

A biphasic nanohydroxyapatite/calcium sulphate carrier containing Rifampicin and Isoniazid for local delivery gives sustained and effective antibiotic release and prevents biofilm formation

“…In the current study, we have used a ceramic based hydroxyapatite bone substitute as a carrier of two first line anti-tuberculosis drugs, Rifampicin and Isoniazid. The potency of a sulphate hydroxyapatite carrier for bioactive molecules to promote bone healing was established in earlier studies 22 , 26 , 39 – 41 . Apart from achieving long term sustained release of drugs, it can act as a bone filler material to fill the dead space at the debrided site.…”

Improved Bone Regeneration in Rabbit Bone Defects Using 3D Printed Composite Scaffolds Functionalized with Osteoinductive Factors

“…The objective of present study was to enhance the limited osteoinductive properties of ceramic-composite scaffolds by functionalizing them with BMP (5 μg/scaffold) and ZA (10 μg/scaffold), and analyze their in vivo applicability. These doses have been found effective for inducing local bone induction and are much lower than the clinically used systemic doses 33,51 . The osteoinductive factors (BMP and ZA) can adsorb on the surface of composites due to their affinity towards incorporated calcium phosphates in addition to being absorbed into the cryogel matrix, providing local delivery of bioactive molecules.…”

“…The commonly used bone filler or stabilization materials (metals, polymer cements, and ceramics) have porosity and bio-degradability issues, affecting and often impeding normal tissue healing. Tissue regeneration requires space for cell migration, matrix deposition, and vascularization, which is inhibited by non-porous and non-degradable implants 32,33 .…”

“…BMP and ZA together acts in a synergistic manner, where BMP induced enhanced bone deposition with ZA mediated inhibition of osteoclast mediated resorption leads to net positive bone deposition 51 . Previously we have evaluated performance of ceramics and cryogel composites thereof, and effects of bioactive molecule functionalization on their in vivo bone formation activities 32,33 . Here, we tried to integrate the previously developed technologies to augment their performance.…”

Platelet-rich plasma-enhanced osseointegration of decellularized bone matrix in critical-size radial defects in rabbits

“…In addition, PRP has been widely used clinically to treat osteoarthritis and rotator cuff injuries (15,16). Previous studies report that PRP could promote bone and cartilage regeneration (17,18).…”