Orthobiologics Offer Patients a Healing Touch

According to a recent Market.us report, the size of the global orthobiologics market is expected to be worth about $14.2 billion by 2033 from $7.9 billion in 2023. This represents a CAGR of 6% during the forecast period from 2024-2033.

Orthobiologics, also known as regenerative cell therapies, contain growth factors to relieve pain, stimulate tissue healing, and reestablish normal function. Orthobiologics come in various types, each with a unique mode of action: viscosupplementation, synthetic biologics, bone growth factors, and demineralized bone matrix (DBM).

Platelet-rich plasma (PRP) therapy is one orthobiologic treatment to treat the injured area and repair broken bones. PRP increases bone intensity and density in the fracture, allowing bone regeneration and recovery for better treatment. Orthobiologic procedures use bone marrow aspiration in many bone injury cases—in the process, a small amount of bone marrow is removed to diagnose and monitor blood and marrow diseases.

This helps to choose which mode of action to be continued for treatment, building up the orthobiologics market. Another significant factor driving their use is the rising prevalence of bone tumors and infections. Other conditions require use of orthobiologics, like different types of traumas, bone lesions, and bone fractures.

“As geriatric patient populations continue to grow and orthopedic injuries remain on the rise, the dominant trends in the orthobiologics market include the growing adoption of viscosupplements for the non-surgical management of pain associated with osteoarthritis, and biointegrative solutions to support healing in orthopedics soft tissue injuries,” Nitin Goyal, M.D., chief science, technology and innovation officer at global orthopedic device maker Zimmer Biomet, told ODT.

Recognizing this trend, in January 2023, Zimmer Biomet fortified its orthobiologics arsenal by acquiring soft-tissue healing company Embody Inc. in a $155 million deal. Embody added a portfolio of collagen-based, biointegrative solutions to treat soft-tissue injuries to the tendon and rotator cuff. Embody’s Tapestry biointegrative implant facilitates tendon healing, and the Tapestry RC arthroscopic implant system is used in rotator cuff repair.

The deal bolstered its orthobiologics portfolio, which already features VISCO-3 Sodium Hyaluronate, a viscosupplement; Gel-One Cross-linked Hyaluronate; GPS III Platelet Concentration System to prepare PRP; the BioCUE Blood and Bone Marrow Aspiration (bBMA) Concentration System; and other solutions.

The company also acquired Avitus Orthopaedics to boost its orthobiologics portfolio about six months ago. The Avitus bone harvester began as an advanced suction curettage device to minimally invasively harvest autologous bone and marrow. The platform has since evolved to streamline bone infection debridement, then further to minimally invasively curettage diseased bone such as osteomyelitis and tumor. Most recently, the company developed an industry-first in percutaneous, autogenous bone delivery with its ArchMIS and DragonWing devices. The suite of technologies integrated into Zimmer Biomet’s platform enables these advanced delivery techniques and the company hopes to establish a new standard for autologous bone and marrow harvesting in orthopedics.

Zimmer Biomet has been partnering with U.K.-based Biocomposites since March 2022, when the company became the exclusive distributor of Biocomposites’ genex Bone Graft Substitute (BGS). genex BGS is a 50:50 biphasic composition of calcium sulfate and β-tricalcium phosphate. It touts a negatively charged surface chemistry that has shown favorable osteogenic bone growth response. Every kit of genex is self-contained, and comes with a radiopaque cannula, delivery syringe, a bead mold tray, and the correct amount of sterile water.

“The genex BGS also totally resorbs in a clinically relevant amount of time—usually around 12 months—with totally healthy, native bone replacing the genex,” said Dr. Goyal. “Zimmer Biomet sees this as the future of orthobiologics—a product implanted by an orthopedic surgeon, selecting the right product for the right patient at the right time, which then is healed and totally resorbed into the patients without leaving a trace.”

Merging Orthobiologics with Digital Health

San Diego, Calif.-based Xenco Medical unveiled its TrabeculeX Continuum at this year’s Consumer Electronic Show (CES). The tool combines the company’s FDA-cleared TrabeculeX Bioactive Matrix and Recovery App to create a bridge between orthobiologics and digital health, unifying biomaterial implantation and the post-op journey.

Surgeons can enroll patients in the app and engage in remote therapeutic monitoring and asynchronous video and text messaging.

“As a digitally-enabled orthobiologic platform, the TrabeculeX Continuum is anchored in longitudinal care and treats patients as partners in recovery, rather than pathologies,” Xenco Medical’s CEO Jason Haider told ODT. “Harmonizing our regenerative biomaterial with our remote therapeutic monitoring technology, the TrabeculeX Continuum works as a seamless link from implantation to full mobility to dissolve the otherwise siloed nature of surgical care.”

Harnessing the hydroxycarbonate apatite-forming capabilities of bioglass, the regenerative biomaterial was engineered to conduct 3D bone formation. Its complex surface topography begins at the sub-micron scale and spans the entire lattice.

“The biomaterial half of the TrabeculeX Continuum orchestrates three-dimensional bone formation through a chemically calibrated interplay between hydroxycarbonate apatite-forming bioactive glass and highly porous, beta-tricalcium phosphate,” explained Haider. “Engineering the architecture of our regenerative biomaterial with a scope that spanned from the sub-micron scale to the lattice itself, it was essential that surface chemistry and surgeon handling considerations worked in concert.”

The company’s Recovery App allows doctors to prescribe and remotely monitor patient-specific physical rehab plans.

“Each TrabeculeX Bioactive Matrix is assigned a unique mobile activation code that enables surgeons to postoperatively enroll patients as users of the TrabeculeX Recovery App, automatically populating the patient’s recovery profile with the size and lot number of the implanted TrabeculeX Bioactive Matrix,” said Haider. “Through our HIPAA-compliant TrabeculeX Recovery App, surgeons can build custom physical therapy programs by drawing from our library of guided video exercises, evaluate symptom analytics, engage in asynchronous video and text messaging, and remotely monitor therapy adherence in graphical form until each patient has returned to full mobility.”

Bio-Inspired Healing Materials

Lowell, Mass.-based RevBio’s TETRANITE is inspired by the Sandcastle Worm, a marine animal. It’s a platform technology biomimetically reverse-engineered from the worm’s secreted protein and has clinical benefits and handling characteristics of wet field adhesion, load bearing strength, and complete osseointegration established by published evidence and global patents. TETRANITE’s formulation is tunable and new clinical applications are in various developmental stages, the company said.

The company is currently conducting FDA-approved TETRANITE clinical studies for dental implant stabilization, extremity fracture repair, vertebral compression repair, dental bone grafting, and pain therapeutics delivery after wisdom tooth extractions.

“Rarely does an opportunity come along to disrupt the standard of care across the range of musculoskeletal uses with a true platform technology,” RevBio CEO Brian Hess told ODT. Our team is purpose-built and committed to taking our novel technology from clinical stage to the widespread transformation of bone repair.”

TETRANITE isn’t just a glue. It’s a regenerative material that can immediately bond bone fragments to boost metal hardware strength and fill gaps in bones. It acts as a scaffold to encourage new bone growth and integrates into the body’s natural healing process. It’s injectable, self-sets, is biocompatible, has bone regenerative capabilities, and touts strength comparable to natural bone, according to the company.

RevBio said TETRANITE’s clinical implications are vast. It can mean fewer complications like non-union, mal-union, post-traumatic osteoarthritis hardware failure, limited range of motion, less pain, and quicker recovery times. The company believes it could replace the need for metal hardware—a huge step forward for orthopedic surgery.

“Our pre-clinical studies have demonstrated TETRANITE can redistribute most of the load from plates and screws, reducing the likelihood of hardware failure and delayed healing,” said Brittany McDonough, RevBio’s R&D program manager, who has led development of the fracture fixation product. “This adhesive material also provides a resorbable scaffold for the regeneration of bone, which accelerates healing within the first few weeks following a traumatic injury. Our next milestone is to translate these positive results for the treatment of extremity fractures in humans.”

Last year, RevBio won a grant from the National Institutes of Health through its Helping to End Addiction Long-term (NIH HEAL) Initiative to improve strategies for preventing and treating opioid misuse and addiction. The $2 million Phase II Small Business Innovation Research (SBIR) grant is funding pre-clinical development of a bone graft formulation that includes release of locally acting, non-opioid pain medication.

The product is meant to fill extraction site and mitigate post-op pain after wisdom tooth removal.

“Preliminary studies have shown medication can be incorporated into our patented TETRANITE bone adhesive biomaterial and released over time,” said Rahul Jadia, Ph.D., RevBio’s R&D manager of technology development and co-principal investigator for the grant. “The release profile of a target drug can be tailored to elicit an ideal time-dose curve.”

As if the severe pain from surgery isn’t enough, 10% of wisdom tooth extractions develop painful “dry socket” that can happen three to four days after extraction. This occurs when the blood clot that should form after tooth extraction is dislodged or dissolves before the wound heals, exposing underlying nerves and bones.

“Data shows there is a statistically significant absolute risk increase in persistent opioid use and abuse following a single course of opiates prescribed after wisdom tooth extractions,” said George Kay, DMD, MMSc, RevBio’s chief scientific officer and co-principal investigator.

Putting on a Thinking CaP

Calcium phosphate (CaP) materials have been used as implant materials since early 1970s research showed the materials’ biocompatibility and utility. There is a diversity of chemical and structural variation in the class of calcium phosphates called orthophosphates.

Calcium phosphates are the major inorganic component of bone tissues. They have a range of applications in the human body, including orthopedics and dentistry. Bone void fillers, hydroxyapatite coatings on metal implant surfaces, and bone cements are applications where calcium phosphate’s biocompatibility, osseointegration potential, and mechanical properties offer a solution to clinical needs.

“Using calcium phosphate coating enhances the osseointegration process for implants, allowing more immediate loading and allowing formation of surrounding bone,” said Onno Visser, managing director of CaP Biomaterials, an East Troy, Wis.-based manufacturer of custom fabricated calcium phosphate products for biomedical applications. “Using synthetic calcium phosphate bone void fillers offers several advantages, including reducing the need for harvesting bone from the patient and decreased risk of infection compared to allografts or xenografts.”

Toxicity studies on this class of bioceramics showed high biocompatibility as well as minimal—if any—inflammatory or foreign body response. They also show no evidence of local or systemic toxicity.

The most commonly used bioceramics are hydroxyapatite, β-tricalcium phosphate, and mixtures of hydroxyapatite and β-tricalcium phosphate—typically referred to as biphasic HA/TCP.

“These materials can be manufactured at scale, reducing supply issues. There have been significant advances in understanding the pathways that allow bone growth, which has led to more advanced approaches in designing bone void fillers and coatings with calcium phosphates,” said Visser. “Gaining an understanding of how nanoscale structures, chemical composition, and ion-substitution affect bone formation pathways are what device designers bring to the table. This means that the level of control required by the contract manufacturer has seen significant increases, with the introduction and refinement of manufacturing methods and analytical capabilities.”

Usually, customers approach a partner like CaP Biomaterials with a prototype made at small scale. They are looking to cooperate in order to establish a robust manufacturing process in an ISO 13485-certified manufacturing setup.

“This isn’t always straightforward—there might be several iterations of the process and the materials manufactured before agreeing on a design freeze and execution of pre-clinical trials required for regulatory approval,” said Visser. “With the increased focus on supply chain robustness a thorough review of the raw material supply chain is to be considered, including pursuing dual sourcing for critical materials.”

In September 2023, Zimmer Biomet began a partnership with PUR Biologics, a subsidiary of HippoFi. The duo plans to introduce a novel synthetic biomaterial for bone growth that’s currently set for a 2024 launch under PUR Biologics.

HippoFi/PUR has FDA 510(k) clearance for ActiveOrb, a disruptive technology in spinal biologics. It secured an exclusive global license to the underlying technology for the spine market from Zimmer Biomet. The two also began a joint commercialization research agreement, with Zimmer Biomet overseeing production of the spine-specific product under the PUR Biologics brand. The company told ODT that its partnership with HippoFi and PUR Biologics will support ongoing development and applications for its unique CaP Spheres synthetic bone graft substitute platform.

The company’s CaP Spheres Pellet Pack is a synthetic, osteoconductive, resorbable bone filler device that consists of hollow and microporous calcium phosphate spheres contained in a resorbable mesh pouch to aid in intraoperative handline. Used as a bone void filler for bony voids or gaps not intrinsic to the bony structure’s stability, CaP Spheres can be implanted directly or hydrated with saline or autologous blood and is meant to be combined with autograft.

The Future of Orthobiologics

In the near future, according to Zimmer Biomet, orthobiologics will be largely shaped by innovations and enhancements in the regenerative medicine space. More technologies moving into pivotal trials that intervene in disease progression, rather than trying to reduce pain, will also be a significant strategy for the market’s future.

“When combined with widespread adoption of innovative new technologies like AI, patient-specific procedures, and smart implants, advancements in orthobiologics technology will not only accelerate progress in new areas of surgery, but will also allow surgeons to proceed with the right procedure for the right patient,” said Dr Goyal. “Surgeons will be able to identify the best type of biologics treatment more properly based on their patient’s specific needs and monitor patient recovery in real-time to ensure the biologics treatment is working, or to help surgeons recognize how and where to reevaluate a procedure.”

Fostering the integration of technology and collaborations between orthopedics and biologics developers will also advance innovation in orthobiologics. That way, they can be made available to a wider variety of procedures and become more affordable for patients.

“The bridging of orthobiologics and digital health recognizes surgical technologies must reflect the timescale of care as well,” said Haider. “It’s essential patients are treated with expansive interventions that reject the prospect of recovering in near isolation. Rather than accepting sparse, punctuating opportunities to share and gather feedback on progress as the standard of care, the unifying bridge of the TrabeculeX Continuum is designed to ensure the aspiration intrinsic to biomaterial implantation is fulfilled throughout the true course of recovery.”