Microencapsulated Transduced Cells for Localized Bone Formation
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Solution Overview
Problem
Conventional methods for delivering bone morphogenetic proteins (BMPs) to induce bone formation face challenges such as rapid clearance, adverse immune responses, and the need for invasive surgeries, leading to inconsistent efficacy and increased costs due to the use of non-biological implants and collagen carriers that bind BMPs, reducing their bioavailability.
Innovation Solution
A cell-based gene therapy system using microencapsulated adenovirus- or adeno-associated virus-transduced cells in poly(ethylene glycol) diacrylate (PEG-DA) hydrogels is delivered to targeted bone defects, allowing for prolonged BMP production and localized bone formation without invasive surgery, using degradable hydrogel carriers that avoid immune responses and maintain BMP bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If isolated recombinant human BMP (rhBMP) is administered in solution to induce bone growth, then bone formation is initiated, but the BMP is rapidly cleared by the patient's body and diffuses from the desired site, reducing efficacy and requiring larger doses
Solution Approach 1:
The patent uses cell-based gene therapy systems as intermediaries to deliver BMPs. Instead of administering BMP directly in solution, the system transduces cells to produce BMP locally at the target site, solving the rapid clearance and diffusion problems while maintaining consistent therapeutic effect
Solution Approach 2:
The transduced cells serve themselves by continuously producing and secreting BMP at the implantation site. This self-service mechanism eliminates the need for external BMP administration and ensures sustained local production without rapid clearance issues
2Reliability
If large quantities of purified BMPs are administered to compensate for rapid diffusion, then satisfactory bone healing is achieved, but the grafting procedures become very expensive
Solution Approach 1:
The transduced cells continuously produce BMP locally, eliminating the need for large quantities of expensive purified BMP. This self-service approach reduces material costs while maintaining reliable bone healing efficacy
3Productivity
If high dosage of BMP (supra-physiologic concentrations) is administered, then bone formation is enhanced, but adverse effects such as soft tissue edema, erythema, local inflammation, immune response, and bone resorption occur
Solution Approach 1:
The patent achieves high BMP production locally at the implantation site through transduced cells, rather than administering high doses systemically. This localized production enhances bone formation while avoiding the adverse effects associated with supra-physiologic concentrations
Solution Approach 2:
The transduced cells self-regulate BMP production at appropriate local concentrations, avoiding the harmful effects of excessive BMP while maintaining effective bone formation rates
4Duration of action of moving object
If collagen carriers are used to retain BMP at implantation sites, then BMP retention is improved, but the collagen binds BMP and reduces its bioavailability
Solution Approach 1:
The transduced cells continuously produce and secrete BMP without requiring external carriers for retention. This eliminates the bioavailability reduction caused by carrier binding while maintaining prolonged BMP presence through continuous cellular production
5Reliability
If invasive surgeries are performed for bone grafting and spinal fusions, then bone repair is achieved, but patient suffering increases and recovery time is extended
Solution Approach 1:
The transduced cells continuously produce BMP at the implantation site, promoting natural bone formation without requiring invasive surgical interventions. This reduces patient suffering and recovery time while achieving reliable bone repair outcomes
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables efficient, localized, and prolonged delivery of BMPs, reducing the need for invasive procedures and minimizing adverse reactions, achieving effective bone formation and fusion with high transduction efficiencies and minimal immune response, thus improving the consistency and cost-effectiveness of bone regeneration therapies.
Implementation Method 1
microencapsulated adenovirus- or adeno-associated virus-transduced cells
Implementation Method 2
allowing for prolonged BMP production
Implementation Method 3
poly(ethylene glycol) diacrylate (PEG-DA) hydrogels
Implementation Method 4
degradable hydrogel carriers
Data Source
AI summary
A method and system to induce bone growth by locally delivering bone morphogenetic proteins (BMPs) to the target location for a prolonged period without invasive procedures are disclosed. The new bone growth is induced by delivering cells producing BMPs from transduced viral vectors to the target cite. In various embodiments, the cells are encapsulated in hydrogel microspheres that are non-degradable or degradable by enzymes produced during the bone formation process. Various embodiments may be used to induce spinal fusion or repair critical bone defects.